1Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. 2Department of Surgical Oncology, Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China. 4Burrell College of Osteopathic Medicine, Las Cruces, USA. 5Center for Neuroscience Research, School of Medicine, Loma Linda University, Loma Linda, CA, USA. 6Brain Research Institute, Zhejiang University, Zhejiang, China. 7Collaborative Innovation Center for Brain Science, Zhejiang University, Zhejiang, China.
Epidemiologic studies have shown that in the aging society, a person dies from stroke every 3 minutes and 42 seconds, and vast numbers of people experience depression around the globe. The high prevalence and disability rates of stroke and depression introduce enormous challenges to public health. Accumulating evidence reveals that stroke is tightly associated with depression, and both diseases are linked to oxidative stress (OS). This review summarizes the mechanisms of OS and OS-mediated pathological processes, such as inflammation, apoptosis, and the microbial-gut-brain axis in stroke and depression. Pathological changes can lead to neuronal cell death, neurological deficits, and brain injury through DNA damage and the oxidation of lipids and proteins, which exacerbate the development of these two disorders. Additionally, aging accelerates the progression of stroke and depression by overactive OS and reduced antioxidant defenses. This review also discusses the efficacy and safety of several antioxidants and antidepressants in stroke and depression. Herein, we propose a crosstalk between OS, aging, stroke, and depression, and provide potential therapeutic strategies for the treatment of stroke and depression.
Figure 1. Schematic model of the main source of ROS and redox reaction. ROS are generated mainly from enzymatic reactions in the cytoplasm, endoplasmic reticulum, mitochondria, and peroxisome . Specifically, overproduced mitoROS can affect metabolic pathways, such as alteration of protein translation, oxidation of lipid and DNA, and impairment of ATP synthesis . Moreover, assembled NOX (NOX1 and NOX2) complex transports an electron from cytosolic NADPH to oxygen to form superoxide on the extracellular side . The NOX4 complex rapidly converts the superoxide to H2O2, which undergoes a Fenton reaction to produce hydroxyl radicals and ions, and to regulate many downstream effects . However, these oxidative events are inhibited by antioxidants, such as SOD and CAT/GPx. Activation of Nrf2-ARE pathway increases antioxidants, such as HO-1, SOD1, and CAT to protect cells from FR accumulation .
Figure 2. Pathogenesis and correlation between stroke and depression. There are different mechanisms in ischemic stroke , ICH , SAH , and depression . Stroke and depression are associated with oxidative stress. Due to overactive OS activity and impaired anti-OS defenses, 16-30% of ischemic stroke survivors [31, 32], 25% of ICH  patients, and 50% of SAH  patients may develop depression later, but the age groups vary among studies. Conversely, depression increases the risk of stroke by 33% in patients who experience stressful life events .
Figure 3. Mechanism of oxidative stress in ischemic stroke.
Figure 4. Schematic model of oxidative mechanisms in ICH and SAH, especially associated with hemoglobin (Hb). During the hemoglobin-heme-iron axis, Hb is released into the extracellular space and is accompanied by an abundance of superoxide generated from the non-enzymatic oxidation of Hb . This oxidation of Hb produces methemoglobin, which releases heme to stimulate lipid peroxidation and other oxidative actions around the hematoma in brain tissue. Meanwhile, iron released from Hb degradation is used in the Fenton reaction to transform H2O2 into the hydroxyl radical, leading to increased oxidative damage .
Figure 5. Mechanisms of oxidative stress and OS-mediated cell death pathway in depression.
Figure 6. Proposed crosslink and interplay among aging, oxidative stress, stroke and depression.
Mechanism of anti-OS activity and others
inhibit OS via Nrf2/HO-1 signaling pathway
Korean Red Ginseng
upregulate Nrf2 pathway and expression levels of BDNF
AMPK-Nrf2 pathway activation, without any toxicity after penetrating the brain
up-regulate Nrf2/HO-1 expression via regulation of p38 MAPK
reduce proinflammatory factors; restore the diminished Akt signaling pathway; faciliate astrocyte proliferation and neurogenesis
modulate NF-κB p65, COX-2 and phosphorylated JNK levels
inhibit OS and inflammation
increase glutamate release; affect energy metabolism
mitochondrial uncoupling protein 2
anti-OS; anti-inflammation; anti-apoptosis
downregulate the activation of NLRP3 inflammasome; suppress the ROS-TXNIP-NLRP3 pathway in astrocytes
inhibit OS, inflammatory responses and apoptosis
reduce neuroinflammation, OS, iron overaccumulation; inhibit neuronal apoptosis in the hippocampus
suppress the apoptosis of hippocampus cells via regulation of Bcl-2/Bax pathways
Table 2 Antioxidants in Depression.
Co-antioxidants in stroke and depression from experiments
Clinical trials and outcomes in stroke
Clinical trials and outcomes in depression
high flavonoid reduces risk of stroke
higher flavonoid links to lower depression risk especially among women
RCT and URICOICTUS
UA is safe; UA enhances outcomes of stroke
cohort studies and meta-analysis
UA are associated with low risk of depression hospitalization and lower MDA levels
early melatonin usage ameliorates the brain injury of asphyxial newborns
buspirone-melatonin therapy benefits cognitive function
melatonin does not affect mood disorders
Table 3 Co-antioxidants in stroke and depression from experiments.
Antioxidants in PSD
not support routine use of fluoxetine in preventing PSD or promoting function recovery
meta-analysis of 12 trials
fluoxetine is the worst choice for PSD treatment; paroxetine is the best drug in terms of efficacy and acceptability
meta-analysis of 20 RCTs
citalopram has similar efficacy and safety as other SSRIs but acts faster than them
exhibit a positive connection between motor recovery
escitalopram is the best tolerated SSRI, followed by sertraline and paroxetine for PSD
not take effects on depressive symptoms; diarrhea is more likely to occur
effective at decreasing the incidence of depression in nondepressed patients
safe for patients with acute ischemic stroke
different effects in different stages of PSD
SSRI treatment is well tolerated and beneficial in PSD
registry-based score-matched follow-up study
pre-stroke SSRI use increases risk of the hemorrhagic stroke; no increased stroke severity and mortality ischemic stroke
milnacipran prevents post-stroke depression; safe to use without serious adverse events
Table 4 Antidepressants in PSD treatment.
Newgard CB, Sharpless NE (2013). Coming of age: molecular drivers of aging and therapeutic opportunities. J Clin Invest, 123:946-950.
Roy-O'Reilly M, McCullough LD (2018). Age and Sex Are Critical Factors in Ischemic Stroke Pathology. Endocrinology, 159:3120-3131.
Schaakxs R, Comijs HC, Lamers F, Kok RM, Beekman ATF, Penninx B (2018). Associations between age and the course of major depressive disorder: a 2-year longitudinal cohort study. Lancet Psychiatry, 5:581-590.
Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. (2019). Heart Disease and Stroke Statistics-2019 Update: A Report From the American Heart Association. Circulation, 139:e56-e528.
DALYs GBD, Collaborators H (2018). Global, regional, and national disability-adjusted life-years (DALYs) for 359 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392:1859-1922.
Collaborators GBDCoD (2018). Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392:1736-1788.
Disease GBD, Injury I, Prevalence C (2017). Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet, 390:1211-1259.
Kessler RC, Bromet EJ (2013). The epidemiology of depression across cultures. Annu Rev Public Health, 34:119-138.
Bromet E, Andrade LH, Hwang I, Sampson NA, Alonso J, de Girolamo G, et al. (2011). Cross-national epidemiology of DSM-IV major depressive episode. BMC Med, 9:90.
Malhi GS, Mann JJ (2018). Depression. Lancet, 392:2299-2312.
Herrman H, Kieling C, McGorry P, Horton R, Sargent J, Patel V (2019). Reducing the global burden of depression: a Lancet-World Psychiatric Association Commission. Lancet, 393:e42-e43.
Ago T, Kuroda J, Pain J, Fu C, Li H, Sadoshima J (2010). Upregulation of Nox4 by hypertrophic stimuli promotes apoptosis and mitochondrial dysfunction in cardiac myocytes. Circ Res, 106:1253-1264.
Bedard K, Krause KH (2007). The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev, 87:245-313.
Sivandzade F, Bhalerao A, Cucullo L (2019). Cerebrovascular and Neurological Disorders: Protective Role of NRF2. Int J Mol Sci, 20.
Moylan S, Berk M, Dean OM, Samuni Y, Williams LJ, O'Neil A, et al. (2014). Oxidative & nitrosative stress in depression: why so much stress? Neurosci Biobehav Rev, 45:46-62.
Jiang X, Andjelkovic AV, Zhu L, Yang T, Bennett MVL, Chen J, et al. (2018). Blood-brain barrier dysfunction and recovery after ischemic stroke. Prog Neurobiol, 163-164:144-171.
Xi G, Keep RF, Hoff JT (2006). Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol, 5:53-63.
Zolnourian A, Galea I, Bulters D (2019). Neuroprotective Role of the Nrf2 Pathway in Subarachnoid Haemorrhage and Its Therapeutic Potential. Oxid Med Cell Longev, 2019:6218239.
Zuo G, Zhang T, Huang L, Araujo C, Peng J, Travis Z, et al. (2019). Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP/PKCepsilon/ALDH2 pathway after subarachnoid hemorrhage in rats. Free Radic Biol Med, 143:441-453.
Song Y, Cao W, Zhu X, Qiu Z, Yang X, Liu J, et al. (2017). F10, a novel hydatidiform mole-associated gene, inhibits the paclitaxel sensitivity of A549 lung cancer cells by downregulating BAX and caspase-3. Oncol Lett, 13:2563-2568.
Keller J, Gomez R, Williams G, Lembke A, Lazzeroni L, Murphy GM Jr, et al. (2017). HPA axis in major depression: cortisol, clinical symptomatology and genetic variation predict cognition. Mol Psychiatry, 22:527-536.
Setiawan E, Wilson AA, Mizrahi R, Rusjan PM, Miler L, Rajkowska G, et al. (2015). Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry, 72:268-275.
Schmaal L, Hibar DP, Samann PG, Hall GB, Baune BT, Jahanshad N, et al. (2017). Cortical abnormalities in adults and adolescents with major depression based on brain scans from 20 cohorts worldwide in the ENIGMA Major Depressive Disorder Working Group. Mol Psychiatry, 22:900-909.
Boldrini M, Fulmore CA, Tartt AN, Simeon LR, Pavlova I, Poposka V, et al. (2018). Human Hippocampal Neurogenesis Persists throughout Aging. Cell Stem Cell, 22:589-599 e585.
Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW (2015). Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology, 51:164-175.
Black CN, Bot M, Scheffer PG, Penninx BWJH (2017). Oxidative stress in major depressive and anxiety disorders, and the association with antidepressant use; results from a large adult cohort. Psychological Medicine, 47:936-948.
Lindqvist D, Dhabhar FS, James SJ, Hough CM, Jain FA, Bersani FS, et al. (2017). Oxidative stress, inflammation and treatment response in major depression. Psychoneuroendocrinology, 76:197-205.
Bigornia SJ, Harris WS, Falcon LM, Ordovas JM, Lai CQ, Tucker KL (2016). The Omega-3 Index Is Inversely Associated with Depressive Symptoms among Individuals with Elevated Oxidative Stress Biomarkers. Journal of Nutrition, 146:758-766.
Tsuboi H, Sakakibara H, Tatsumi A, Yamakawa-Kobayashi K, Matsunaga M, Kaneko H, et al. (2019). Serum IL-6 levels and oxidation rate of LDL cholesterol were related to depressive symptoms independent of omega-3 fatty acids among female hospital and nursing home workers in Japan. J Affect Disord, 249:385-393.
Limampai P, Wongsrithep W, Kuptniratsaikul V (2017). Depression after stroke at 12-month follow-up: a multicenter study. International Journal of Neuroscience, 127:887-892.
Shi Y, Xiang Y, Yang Y, Zhang N, Wang S, Ungvari GS, et al. (2015). Depression after minor stroke: Prevalence and predictors. J Psychosom Res, 79:143-147.
Maaijwee NA, Tendolkar I, Rutten-Jacobs LC, Arntz RM, Schaapsmeerders P, Dorresteijn LD, et al. (2016). Long-term depressive symptoms and anxiety after transient ischaemic attack or ischaemic stroke in young adults. Eur J Neurol, 23:1262-1268.
Ackermark PY, Schepers VP, Post MW, Rinkel GJ, Passier PE, Visser-Meily JM (2017). Longitudinal course of depressive symptoms and anxiety after aneurysmal subarachnoid hemorrhage. Eur J Phys Rehabil Med, 53:98-104.
Jackson CA, Mishra GD (2013). Depression and risk of stroke in midaged women: a prospective longitudinal study. Stroke, 44:1555-1560.
Pan A, Sun Q, Okereke OI, Rexrode KM, Hu FB (2011). Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review. JAMA, 306:1241-1249.
Booth J, Connelly L, Lawrence M, Chalmers C, Joice S, Becker C, et al. (2015). Evidence of perceived psychosocial stress as a risk factor for stroke in adults: a meta-analysis. Bmc Neurology, 15.
Wang YZ, Wang JJ, Huang Y, Liu F, Zeng WZ, Li Y, et al. (2015). Tissue acidosis induces neuronal necroptosis via ASIC1a channel independent of its ionic conduction. Elife, 4.
Anwar MA, Eid AH (2016). Determination of Vascular Reactivity of Middle Cerebral Arteries from Stroke and Spinal Cord Injury Animal Models Using Pressure Myography. Methods Mol Biol, 1462:611-624.
Lien LM, Chiou HY, Yeh HL, Chiu SY, Jeng JS, Lin HJ, et al. (2017). Significant Association Between Low Mitochondrial DNA Content in Peripheral Blood Leukocytes and Ischemic Stroke. Journal of the American Heart Association, 6.
Zitnanova I, Siarnik P, Kollar B, Chomova M, Pazderova P, Andrezalova L, et al. (2016). Oxidative Stress Markers and Their Dynamic Changes in Patients after Acute Ischemic Stroke. Oxidative Medicine and Cellular Longevity.
Liu Z, Liu Y, Tu X, Shen H, Qiu H, Chen H, et al. (2017). High Serum Levels of Malondialdehyde and 8-OHdG are both Associated with Early Cognitive Impairment in Patients with Acute Ischaemic Stroke. Sci Rep, 7:9493.
Wang AX, Cui Y, Meng X, Su ZP, Cao YB, Yang YL, et al. (2018). The relationship between oxidized low-density lipoprotein and the NIHSS score among patients with acute ischemic stroke: The SOS-Stroke Study. Atherosclerosis, 270:21-25.
Wang A, Liu J, Meng X, Li J, Wang H, Wang Y, et al. (2018). Association between oxidized low-density lipoprotein and cognitive impairment in patients with ischemic stroke. European Journal of Neurology, 25:185-191.
Wang A, Yang Y, Su Z, Yue W, Hao H, Ren L, et al. (2017). Association of Oxidized Low-Density Lipoprotein With Prognosis of Stroke and Stroke Subtypes. Stroke, 48:91-97.
Huang FP, Xi G, Keep RF, Hua Y, Nemoianu A, Hoff JT (2002). Brain edema after experimental intracerebral hemorrhage: role of hemoglobin degradation products. J Neurosurg, 96:287-293.
Chen Q, Tang J, Tan L, Guo J, Tao Y, Li L, et al. (2015). Intracerebral Hematoma Contributes to Hydrocephalus After Intraventricular Hemorrhage via Aggravating Iron Accumulation. Stroke, 46:2902-2908.
Wu H, Wu T, Li M, Wang J (2012). Efficacy of the lipid-soluble iron chelator 2,2'-dipyridyl against hemorrhagic brain injury. Neurobiol Dis, 45:388-394.
Neves JD, Vizuete AF, Nicola F, Da Re C, Rodrigues AF, Schmitz F, et al. (2018). Glial glutamate transporters expression, glutamate uptake, and oxidative stress in an experimental rat model of intracerebral hemorrhage. Neurochem Int, 116:13-21.
Katsu M, Niizuma K, Yoshioka H, Okami N, Sakata H, Chan PH (2010). Hemoglobin-induced oxidative stress contributes to matrix metalloproteinase activation and blood-brain barrier dysfunction in vivo. J Cereb Blood Flow Metab, 30:1939-1950.
Wang Z, Zhou F, Dou Y, Tian X, Liu C, Li H, et al. (2018). Melatonin Alleviates Intracerebral Hemorrhage-Induced Secondary Brain Injury in Rats via Suppressing Apoptosis, Inflammation, Oxidative Stress, DNA Damage, and Mitochondria Injury. Transl Stroke Res, 9:74-91.
Meng C, Zhang J, Dang B, Li H, Shen H, Li X, et al. (2018). PERK Pathway Activation Promotes Intracerebral Hemorrhage Induced Secondary Brain Injury by Inducing Neuronal Apoptosis Both in Vivo and in Vitro. Front Neurosci, 12:111.
Zhang Z, Song Y, Zhang Z, Li D, Zhu H, Liang R, et al. (2017). Distinct role of heme oxygenase-1 in early- and late-stage intracerebral hemorrhage in 12-month-old mice. J Cereb Blood Flow Metab, 37:25-38.
Zetterling M, Hallberg L, Ronne-Engstrom E (2010). Early global brain oedema in relation to clinical admission parameters and outcome in patients with aneurysmal subarachnoid haemorrhage. Acta Neurochir (Wien), 152:1527-1533; discussion 1533.
Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, et al. (2010). Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke, 41:2391-2395.
Zhang HM, Sang XG, Wang YZ, Cui C, Zhang L, Ji WS (2017). Role of Delta133p53 isoform in NF-kappaB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells. World J Gastroenterol, 23:2716-2722.
Zhong JT, Yu J, Wang HJ, Shi Y, Zhao TS, He BX, et al. (2017). Effects of endoplasmic reticulum stress on the autophagy, apoptosis, and chemotherapy resistance of human breast cancer cells by regulating the PI3K/AKT/mTOR signaling pathway. Tumour Biol, 39:1010428317697562.
Shi X, Fu Y, Zhang S, Ding H, Chen J (2017). Baicalin Attenuates Subarachnoid Hemorrhagic Brain Injury by Modulating Blood-Brain Barrier Disruption, Inflammation, and Oxidative Damage in Mice. Oxid Med Cell Longev, 2017:1401790.
Fan LF, He PY, Peng YC, Du QH, Ma YJ, Jin JX, et al. (2017). Mdivi-1 ameliorates early brain injury after subarachnoid hemorrhage via the suppression of inflammation-related blood-brain barrier disruption and endoplasmic reticulum stress-based apoptosis. Free Radic Biol Med, 112:336-349.
Han Y, Su J, Liu X, Zhao Y, Wang C, Li X (2017). Naringin alleviates early brain injury after experimental subarachnoid hemorrhage by reducing oxidative stress and inhibiting apoptosis. Brain Res Bull, 133:42-50.
Dou Y, Shen H, Feng D, Li H, Tian X, Zhang J, et al. (2017). Tumor necrosis factor receptor-associated factor 6 participates in early brain injury after subarachnoid hemorrhage in rats through inhibiting autophagy and promoting oxidative stress. J Neurochem, 142:478-492.
Wu H, Niu H, Wu C, Li Y, Wang K, Zhang J, et al. (2016). The autophagy-lysosomal system in subarachnoid haemorrhage. J Cell Mol Med, 20:1770-1778.
Barnes J, MondeIli V, Pariante CM (2017). Genetic Contributions of Inflammation to Depression. Neuropsychopharmacology, 42:81-98.
Amidfar M, Kim YK, Scaini G, Quevedo J (2018). Evidence for additionally increased apoptosis in the peripheral blood mononuclear cells of major depressive patients with a high risk for suicide. Am J Med Genet B Neuropsychiatr Genet, 177:388-396.
Mayer EA, Tillisch K, Gupta A (2015). Gut/brain axis and the microbiota. J Clin Invest, 125:926-938.
Ibi M, Liu J, Arakawa N, Kitaoka S, Kawaji A, Matsuda KI, et al. (2017). Depressive-Like Behaviors Are Regulated by NOX1/NADPH Oxidase by Redox Modification of NMDA Receptor 1. J Neurosci, 37:4200-4212.
Koo YS, Kim H, Park JH, Kim MJ, Shin YI, Choi BT, et al. (2018). Indoleamine 2,3-Dioxygenase-Dependent Neurotoxic Kynurenine Metabolism Contributes to Poststroke Depression Induced in Mice by Ischemic Stroke along with Spatial Restraint Stress. Oxid Med Cell Longev, 2018:2413841.
Kudlow P, Cha DS, Carvalho AF, McIntyre RS (2016). Nitric Oxide and Major Depressive Disorder: Pathophysiology and Treatment Implications. Curr Mol Med, 16:206-215.
Rezin GT, Cardoso MR, Goncalves CL, Scaini G, Fraga DB, Riegel RE, et al. (2008). Inhibition of mitochondrial respiratory chain in brain of rats subjected to an experimental model of depression. Neurochem Int, 53:395-400.
Pasquali MA, Harlow BL, Soares CN, Otto MW, Cohen LS, Minuzzi L, et al. (2018). A longitudinal study of neurotrophic, oxidative, and inflammatory markers in first-onset depression in midlife women. Eur Arch Psychiatry Clin Neurosci, 268:771-781.
Vavakova M, Durackova Z, Trebaticka J (2015). Markers of Oxidative Stress and Neuroprogression in Depression Disorder. Oxid Med Cell Longev, 2015:898393.
Wigner P, Czarny P, Synowiec E, Bijak M, Bialek K, Talarowska M, et al. (2018). Variation of genes involved in oxidative and nitrosative stresses in depression. Eur Psychiatry, 48:38-48.
Jimenez-Fernandez S, Gurpegui M, Diaz-Atienza F, Perez-Costillas L, Gerstenberg M, Correll CU (2015). Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: results from a meta-analysis. J Clin Psychiatry, 76:1658-1667.
Moreno-Fernandez AM, Cordero MD, Garrido-Maraver J, Alcocer-Gomez E, Casas-Barquero N, Carmona-Lopez MI, et al. (2012). Oral treatment with amitriptyline induces coenzyme Q deficiency and oxidative stress in psychiatric patients. J Psychiatr Res, 46:341-345.
Jimenez-Fernandez S, Gurpegui M, Diaz-Atienza F, Perez-Costillas L, Gerstenberg M, Correll CU (2015). Oxidative Stress and Antioxidant Parameters in Patients With Major Depressive Disorder Compared to Healthy Controls Before and After Antidepressant Treatment: Results From a Meta-Analysis. Journal of Clinical Psychiatry, 76:1658-+.
Gotschel F, Kern C, Lang S, Sparna T, Markmann C, Schwager J, et al. (2008). Inhibition of GSK3 differentially modulates NF-kappaB, CREB, AP-1 and beta-catenin signaling in hepatocytes, but fails to promote TNF-alpha-induced apoptosis. Exp Cell Res, 314:1351-1366.
Rana AK, Singh D (2018). Targeting glycogen synthase kinase-3 for oxidative stress and neuroinflammation: Opportunities, challenges and future directions for cerebral stroke management. Neuropharmacology, 139:124-136.
Chen X, Liu Y, Zhu J, Lei S, Dong Y, Li L, et al. (2016). GSK-3beta downregulates Nrf2 in cultured cortical neurons and in a rat model of cerebral ischemia-reperfusion. Sci Rep, 6:20196.
Qiu J, Nishimura M, Wang Y, Sims JR, Qiu S, Savitz SI, et al. (2008). Early release of HMGB-1 from neurons after the onset of brain ischemia. J Cereb Blood Flow Metab, 28:927-938.
Qiu J, Xu J, Zheng Y, Wei Y, Zhu X, Lo EH, et al. (2010). High-mobility group box 1 promotes metalloproteinase-9 upregulation through Toll-like receptor 4 after cerebral ischemia. Stroke, 41:2077-2082.
Martin M, Rehani K, Jope RS, Michalek SM (2005). Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol, 6:777-784.
Iadecola C, Anrather J (2011). The immunology of stroke: from mechanisms to translation. Nat Med, 17:796-808.
Perez-de-Puig I, Miro-Mur F, Ferrer-Ferrer M, Gelpi E, Pedragosa J, Justicia C, et al. (2015). Neutrophil recruitment to the brain in mouse and human ischemic stroke. Acta Neuropathol, 129:239-257.
Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 464:104-107.
Kohler O, Krogh J, Mors O, Benros ME (2016). Inflammation in Depression and the Potential for Anti-Inflammatory Treatment. Curr Neuropharmacol, 14:732-742.
Jiang XP, Elliott RL (2017). Decreased Iron in Cancer Cells and Their Microenvironment Improves Cytolysis of Breast Cancer Cells by Natural Killer Cells. Anticancer Res, 37:2297-2305.
Zhou R, Yazdi AS, Menu P, Tschopp J (2011). A role for mitochondria in NLRP3 inflammasome activation. Nature, 469:221-225.
Alcocer-Gomez E, de Miguel M, Casas-Barquero N, Nunez-Vasco J, Sanchez-Alcazar JA, Fernandez-Rodriguez A, et al. (2014). NLRP3 inflammasome is activated in mononuclear blood cells from patients with major depressive disorder. Brain Behav Immun, 36:111-117.
Roomruangwong C, Anderson G, Berk M, Stoyanov D, Carvalho AF, Maes M (2018). A neuro-immune, neuro-oxidative and neuro-nitrosative model of prenatal and postpartum depression. Prog Neuropsychopharmacol Biol Psychiatry, 81:262-274.
Anderson G (2018). Linking the biological underpinnings of depression: Role of mitochondria interactions with melatonin, inflammation, sirtuins, tryptophan catabolites, DNA repair and oxidative and nitrosative stress, with consequences for classification and cognition. Prog Neuropsychopharmacol Biol Psychiatry, 80:255-266.
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G (2010). Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol, 11:700-714.
Unal-Cevik I, Kilinc M, Can A, Gursoy-Ozdemir Y, Dalkara T (2004). Apoptotic and necrotic death mechanisms are concomitantly activated in the same cell after cerebral ischemia. Stroke, 35:2189-2194.
Wang P, Shao BZ, Deng Z, Chen S, Yue Z, Miao CY (2018). Autophagy in ischemic stroke. Prog Neurobiol, 163-164:98-117.
Culmsee C, Zhu C, Landshamer S, Becattini B, Wagner E, Pellecchia M, et al. (2005). Apoptosis-inducing factor triggered by poly(ADP-ribose) polymerase and Bid mediates neuronal cell death after oxygen-glucose deprivation and focal cerebral ischemia. J Neurosci, 25:10262-10272.
Yu A, Zhang T, Zhong W, Duan H, Wang S, Ye P, et al. (2017). miRNA-144 induces microglial autophagy and inflammation following intracerebral hemorrhage. Immunol Lett, 182:18-23.
Shen X, Ma L, Dong W, Wu Q, Gao Y, Luo C, et al. (2016). Autophagy regulates intracerebral hemorrhage induced neural damage via apoptosis and NF-kappaB pathway. Neurochem Int, 96:100-112.
McKernan DP, Dinan TG, Cryan JF (2009). "Killing the Blues": a role for cellular suicide (apoptosis) in depression and the antidepressant response? Prog Neurobiol, 88:246-263.
Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, et al. (1995). Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell, 80:279-284.
Harlan J, Chen Y, Gubbins E, Mueller R, Roch JM, Walter K, et al. (2006). Variants in Apaf-1 segregating with major depression promote apoptosome function. Mol Psychiatry, 11:76-85.
Dumitrescu L, Popescu-Olaru I, Cozma L, Tulba D, Hinescu ME, Ceafalan LC, et al. (2018). Oxidative Stress and the Microbiota-Gut-Brain Axis. Oxidative Medicine and Cellular Longevity.
Bonaz B, Bazin T, Pellissier S (2018). The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Frontiers in Neuroscience, 12.
Martino R, Foley N, Bhogal S, Diamant N, Speechley M, Teasell R (2005). Dysphagia after stroke: incidence, diagnosis, and pulmonary complications. Stroke, 36:2756-2763.
Harari D, Coshall C, Rudd AG, Wolfe CD (2003). New-onset fecal incontinence after stroke: prevalence, natural history, risk factors, and impact. Stroke, 34:144-150.
Su YJ, Zhang XY, Zeng JS, Pei Z, Cheung RTF, Zhou QP, et al. (2009). New-Onset Constipation at Acute Stage After First Stroke Incidence, Risk Factors, and Impact on the Stroke Outcome. Stroke, 40:1304-1309.
Wen SW, Wong CHY (2017). An unexplored brain-gut microbiota axis in stroke. Gut Microbes, 8:601-606.
Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, et al. (2016). Commensal microbiota affects ischemic stroke outcome by regulating intestinal gammadelta T cells. Nat Med, 22:516-523.
Rhee SH, Pothoulakis C, Mayer EA (2009). Principles and clinical implications of the brain-gut-enteric microbiota axis. Nat Rev Gastroenterol Hepatol, 6:306-314.
Zheng P, Zeng B, Zhou C, Liu M, Fang Z, Xu X, et al. (2016). Gut microbiome remodeling induces depressive-like behaviors through a pathway mediated by the host's metabolism. Molecular Psychiatry, 21:786-796.
Slyepchenko A, Maes M, Jacka FN, Kohler CA, Barichello T, McIntyre RS, et al. (2017). Gut Microbiota, Bacterial Translocation, and Interactions with Diet: Pathophysiological Links between Major Depressive Disorder and Non-Communicable Medical Comorbidities. Psychother Psychosom, 86:31-46.
Willey JZ, Moon YP, Sacco RL, Greenlee H, Diaz KM, Wright CB, et al. (2017). Physical inactivity is a strong risk factor for stroke in the oldest old: Findings from a multi-ethnic population (the Northern Manhattan Study). International Journal of Stroke, 12:197-200.
Ay H, Arsava EM, Andsberg G, Benner T, Brown RD Jr, Chapman SN, et al. (2014). Pathogenic ischemic stroke phenotypes in the NINDS-stroke genetics network. Stroke, 45:3589-3596.
Howard G, Goff DC (2012). Population shifts and the future of stroke: forecasts of the future burden of stroke. Ann N Y Acad Sci, 1268:14-20.
Sjoberg L, Karlsson B, Atti AR, Skoog I, Fratiglioni L, Wang HX (2017). Prevalence of depression: Comparisons of different depression definitions in population-based samples of older adults. J Affect Disord, 221:123-131.
Ames BN, Shigenaga MK, Hagen TM (1993). Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci U S A, 90:7915-7922.
Floyd RA, Hensley K (2002). Oxidative stress in brain aging. Implications for therapeutics of neurodegenerative diseases. Neurobiol Aging, 23:795-807.
Bettio LEB, Rajendran L, Gil-Mohapel J (2017). The effects of aging in the hippocampus and cognitive decline. Neurosci Biobehav Rev, 79:66-86.
Wu Z, Yu J, Zhu A, Nakanishi H (2016). Nutrients, Microglia Aging, and Brain Aging. Oxid Med Cell Longev, 2016:7498528.
Poulose SM, Miller MG, Scott T, Shukitt-Hale B (2017). Nutritional Factors Affecting Adult Neurogenesis and Cognitive Function. Adv Nutr, 8:804-811.
Corenblum MJ, Ray S, Remley QW, Long M, Harder B, Zhang DD, et al. (2016). Reduced Nrf2 expression mediates the decline in neural stem cell function during a critical middle-age period. Aging Cell, 15:725-736.
Maher P (2018). Potentiation of glutathione loss and nerve cell death by the transition metals iron and copper: Implications for age-related neurodegenerative diseases. Free Radic Biol Med, 115:92-104.
Mattson MP, Arumugam TV (2018). Hallmarks of Brain Aging: Adaptive and Pathological Modification by Metabolic States. Cell Metab, 27:1176-1199.
Ham PB 3rd, Raju R (2017). Mitochondrial function in hypoxic ischemic injury and influence of aging. Prog Neurobiol, 157:92-116.
Rzechorzek W, Zhang H, Buckley BK, Hua K, Pomp D, Faber JE (2017). Aerobic exercise prevents rarefaction of pial collaterals and increased stroke severity that occur with aging. J Cereb Blood Flow Metab, 37:3544-3555.
Graham SH, Liu H (2017). Life and death in the trash heap: The ubiquitin proteasome pathway and UCHL1 in brain aging, neurodegenerative disease and cerebral Ischemia. Ageing Res Rev, 34:30-38.
Badan I, Buchhold B, Hamm A, Gratz M, Walker LC, Platt D, et al. (2003). Accelerated glial reactivity to stroke in aged rats correlates with reduced functional recovery. J Cereb Blood Flow Metab, 23:845-854.
Campuzano O, Castillo-Ruiz MM, Acarin L, Castellano B, Gonzalez B (2009). Increased levels of proinflammatory cytokines in the aged rat brain attenuate injury-induced cytokine response after excitotoxic damage. J Neurosci Res, 87:2484-2497.
Camacho E, LoPresti MA, Bruce S, Lin D, Abraham M, Appelboom G, et al. (2015). The role of age in intracerebral hemorrhages. J Clin Neurosci, 22:1867-1870.
Brown PJ, Rutherford BR, Yaffe K, Tandler JM, Ray JL, Pott E, et al. (2016). The Depressed Frail Phenotype: The Clinical Manifestation of Increased Biological Aging. Am J Geriatr Psychiatry, 24:1084-1094.
Karabatsiakis A, Bock C, Salinas-Manrique J, Kolassa S, Calzia E, Dietrich DE, et al. (2014). Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression. Transl Psychiatry, 4:e397.
Geerlings MI, Gerritsen L (2017). Late-Life Depression, Hippocampal Volumes, and Hypothalamic-Pituitary-Adrenal Axis Regulation: A Systematic Review and Meta-analysis. Biol Psychiatry, 82:339-350.
Volkow ND, Gur RC, Wang GJ, Fowler JS, Moberg PJ, Ding YS, et al. (1998). Association between decline in brain dopamine activity with age and cognitive and motor impairment in healthy individuals. American Journal of Psychiatry, 155:344-349.
Troiano AR, Schulzer M, de la Fuente-Fernandez R, Mak E, McKenzie J, Sossi V, et al. (2010). Dopamine transporter PET in normal aging: dopamine transporter decline and its possible role in preservation of motor function. Synapse, 64:146-151.
van Dyck CH, Avery RA, MacAvoy MG, Marek KL, Quinlan DM, Baldwin RM, et al. (2008). Striatal dopamine transporters correlate with simple reaction time in elderly subjects. Neurobiol Aging, 29:1237-1246.
Visser M, Pahor M, Taaffe DR, Goodpaster BH, Simonsick EM, Newman AB, et al. (2002). Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: the Health ABC Study. J Gerontol A Biol Sci Med Sci, 57:M326-332.
Steptoe A, Deaton A, Stone AA (2015). Subjective wellbeing, health, and ageing. Lancet, 385:640-648.
Ghimire S, Baral BK, Pokhrel BR, Pokhrel A, Acharya A, Amatya D, et al. (2018). Depression, malnutrition, and health-related quality of life among Nepali older patients. Bmc Geriatrics, 18.
Araujo JR, Martel F, Borges N, Araujo JM, Keating E (2015). Folates and aging: Role in mild cognitive impairment, dementia and depression. Ageing Res Rev, 22:9-19.
Mendelsohn AR, Larrick JW (2017). The NAD+/PARP1/SIRT1 Axis in Aging. Rejuvenation Res, 20:244-247.
Xie Q, Peng S, Tao L, Ruan H, Yang Y, Li TM, et al. (2014). E2F transcription factor 1 regulates cellular and organismal senescence by inhibiting Forkhead box O transcription factors. J Biol Chem, 289:34205-34213.
Gonzalez-Giraldo Y, Forero DA, Echeverria V, Gonzalez J, Avila-Rodriguez M, Garcia-Segura LM, et al. (2016). Neuroprotective effects of the catalytic subunit of telomerase: A potential therapeutic target in the central nervous system. Ageing Res Rev, 28:37-45.
Duffy SL, Lagopoulos J, Cockayne N, Hermens DF, Hickie IB, Naismith SL (2015). Oxidative stress and depressive symptoms in older adults: A magnetic resonance spectroscopy study. J Affect Disord, 180:29-35.
Kok RM, Reynolds CF 3rd, (2017). Management of Depression in Older Adults: A Review. JAMA, 317:2114-2122.
Cipriani A, Furukawa TA, Salanti G, Chaimani A, Atkinson LZ, Ogawa Y, et al. (2018). Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet, 391:1357-1366.
Hu L, Chen W, Tian F, Yuan C, Wang H, Yue H (2018). Neuroprotective role of fucoxanthin against cerebral ischemic/reperfusion injury through activation of Nrf2/HO-1 signaling. Biomed Pharmacother, 106:1484-1489.
Zhang W, Wei R, Zhang L, Tan Y, Qian C (2017). Sirtuin 6 protects the brain from cerebral ischemia/reperfusion injury through NRF2 activation. Neuroscience, 366:95-104.
Guo C, Wang S, Duan J, Jia N, Zhu Y, Ding Y, et al. (2017). Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cepsilon/Nrf2/HO-1 Pathway. Mol Neurobiol, 54:833-845.
Yang Z, Weian C, Susu H, Hanmin W (2016). Protective effects of mangiferin on cerebral ischemia-reperfusion injury and its mechanisms. Eur J Pharmacol, 771:145-151.
Liu L, Vollmer MK, Ahmad AS, Fernandez VM, Kim H, Dore S (2019). Pretreatment with Korean red ginseng or dimethyl fumarate attenuates reactive gliosis and confers sustained neuroprotection against cerebral hypoxic-ischemic damage by an Nrf2-dependent mechanism. Free Radical Biology and Medicine, 131:98-114.
Ding Y, Chen MC, Wang MM, Li YW, Wen AD (2015). Posttreatment with 11-Keto-beta-Boswellic Acid Ameliorates Cerebral Ischemia-Reperfusion Injury: Nrf2/HO-1 Pathway as a Potential Mechanism. Molecular Neurobiology, 52:1430-1439.
Ashabi G, Khalaj L, Khodagholi F, Goudarzvand M, Sarkaki A (2015). Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia. Metab Brain Dis, 30:747-754.
Shi H, Jing X, Wei X, Perez RG, Ren M, Zhang X, et al. (2015). S-allyl cysteine activates the Nrf2-dependent antioxidant response and protects neurons against ischemic injury in vitro and in vivo. J Neurochem, 133:298-308.
Singh D, Reeta KH, Sharma U, Jagannathan NR, Dinda AK, Gupta YK (2019). Neuro-protective effect of monomethyl fumarate on ischemia reperfusion injury in rats: Role of Nrf2/HO1 pathway in peri-infarct region. Neurochem Int, 126:96-108.
Cui YJ, Amarsanaa K, Lee JH, Rhim JK, Kwon JM, Kim SH, et al. (2019). Neuroprotective mechanisms of dieckol against glutamate toxicity through reactive oxygen species scavenging and nuclear factor-like 2/heme oxygenase-1 pathway. Korean Journal of Physiology & Pharmacology, 23:121-130.
Lin R, Cai J, Kostuk EW, Rosenwasser R, Iacovitti L (2016). Fumarate modulates the immune/inflammatory response and rescues nerve cells and neurological function after stroke in rats. J Neuroinflammation, 13:269.
Ya BL, Liu Q, Li HF, Cheng HJ, Yu T, Chen L, et al. (2018). Uric Acid Protects against Focal Cerebral Ischemia/Reperfusion-Induced Oxidative Stress via Activating Nrf2 and Regulating Neurotrophic Factor Expression. Oxid Med Cell Longev, 2018:6069150.
Wang Y, Huang Y, Xu Y, Ruan W, Wang H, Zhang Y, et al. (2018). A Dual AMPK/Nrf2 Activator Reduces Brain Inflammation After Stroke by Enhancing Microglia M2 Polarization. Antioxid Redox Signal, 28:141-163.
Yen TL, Chen RJ, Jayakumar T, Lu WJ, Hsieh CY, Hsu MJ, et al. (2016). Andrographolide stimulates p38 mitogen-activated protein kinase-nuclear factor erythroid-2-related factor 2-heme oxygenase 1 signaling in primary cerebral endothelial cells for definite protection against ischemic stroke in rats. Transl Res, 170:57-72.
Lee CT, Yu LE, Wang JY (2016). Nitroxide antioxidant as a potential strategy to attenuate the oxidative/nitrosative stress induced by hydrogen peroxide plus nitric oxide in cultured neurons. Nitric Oxide-Biology and Chemistry, 54:38-50.
Kuo PC, Yu IC, Scofield BA, Brown DA, Curfman ET, Paraiso HC, et al. (2017). 3H-1,2-Dithiole-3-thione as a novel therapeutic agent for the treatment of ischemic stroke through Nrf2 defense pathway. Brain Behav Immun, 62:180-192.
Chen N, Zhou Z, Li J, Li B, Feng J, He D, et al. (2018). 3-n-butylphthalide exerts neuroprotective effects by enhancing anti-oxidation and attenuating mitochondrial dysfunction in an in vitro model of ischemic stroke. Drug Des Devel Ther, 12:4261-4271.
Wu JZ, Jin Z, Yang XR, Yan LJ (2018). Post-ischemic administration of 5-methoxyindole-2-carboxylic acid at the onset of reperfusion affords neuroprotection against stroke injury by preserving mitochondrial function and attenuating oxidative stress. Biochemical and Biophysical Research Communications, 497:444-450.
Yang Y, Jiang S, Dong Y, Fan C, Zhao L, Yang X, et al. (2015). Melatonin prevents cell death and mitochondrial dysfunction via a SIRT1-dependent mechanism during ischemic-stroke in mice. J Pineal Res, 58:61-70.
Andrabi SS, Parvez S, Tabassum H (2017). Progesterone induces neuroprotection following reperfusion-promoted mitochondrial dysfunction after focal cerebral ischemia in rats. Dis Model Mech, 10:787-796.
Silachev DN, Plotnikov EY, Pevzner IB, Zorova LD, Balakireva AV, Gulyaev MV, et al. (2018). Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic(-)Ischemic Brain Injury. Molecules, 23.
Chen M, Zou W, Chen M, Cao L, Ding J, Xiao W, et al. (2018). Ginkgolide K promotes angiogenesis in a middle cerebral artery occlusion mouse model via activating JAK2/STAT3 pathway. Eur J Pharmacol, 833:221-229.
Xie YZ, Zhang XJ, Zhang C, Yang Y, He JN, Chen YX (2019). Protective effects of leonurine against ischemic stroke in mice by activating nuclear factor erythroid 2-related factor 2 pathway. CNS Neurosci Ther.
Li H, Wang P, Huang F, Jin J, Wu H, Zhang B, et al. (2018). Astragaloside IV protects blood-brain barrier integrity from LPS-induced disruption via activating Nrf2 antioxidant signaling pathway in mice. Toxicol Appl Pharmacol, 340:58-66.
Chen Z, Mao X, Liu A, Gao X, Chen X, Ye M, et al. (2015). Osthole, a natural coumarin improves cognitive impairments and BBB dysfunction after transient global brain ischemia in C57 BL/6J mice: involvement of Nrf2 pathway. Neurochem Res, 40:186-194.
Hu S, Wu Y, Zhao B, Hu H, Zhu B, Sun Z, et al. (2018). Panax notoginseng Saponins Protect Cerebral Microvascular Endothelial Cells against Oxygen-Glucose Deprivation/Reperfusion-Induced Barrier Dysfunction via Activation of PI3K/Akt/Nrf2 Antioxidant Signaling Pathway. Molecules, 23.
Li L, Yang N, Nin L, Zhao Z, Chen L, Yu J, et al. (2015). Chinese herbal medicine formula tao hong si wu decoction protects against cerebral ischemia-reperfusion injury via PI3K/Akt and the Nrf2 signaling pathway. J Nat Med, 69:76-85.
Zhou F, Wang M, Ju J, Wang Y, Liu Z, Zhao X, et al. (2019). Schizandrin A protects against cerebral ischemia-reperfusion injury by suppressing inflammation and oxidative stress and regulating the AMPK/Nrf2 pathway regulation. Am J Transl Res, 11:199-209.
Kwon YW, Cheon SY, Park SY, Song J, Lee JH (2017). Tryptanthrin Suppresses the Activation of the LPS-Treated BV2 Microglial Cell Line via Nrf2/HO-1 Antioxidant Signaling. Front Cell Neurosci, 11:18.
Yang MY, Yu QL, Huang YS, Yang G (2019). Neuroprotective effects of andrographolide derivative CX-10 in transient focal ischemia in rat: Involvement of Nrf2/AE and TLR/NF-kappaB signaling. Pharmacol Res, 144:227-234.
Li C, Zhang WJ, Frei B (2016). Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol, 9:104-113.
Zhu SL, Tang SY, Su F (2018). Dioscin inhibits ischemic stroke-induced inflammation through inhibition of the TLR4/MyD88/NF-B signaling pathway in a rat model. Molecular Medicine Reports, 17:660-666.
Hou Y, Wang Y, He Q, Li L, Xie H, Zhao Y, et al. (2018). Nrf2 inhibits NLRP3 inflammasome activation through regulating Trx1/TXNIP complex in cerebral ischemia reperfusion injury. Behav Brain Res, 336:32-39.
Wang WM, Liu Z, Liu AJ, Wang YX, Wang HG, An D, et al. (2015). The Zinc Ion Chelating Agent TPEN Attenuates Neuronal Death/apoptosis Caused by Hypoxia/ischemia Via Mediating the Pathophysiological Cascade Including Excitotoxicity, Oxidative Stress, and Inflammation. CNS Neurosci Ther, 21:708-717.
Yu G, Liang Y, Zheng S, Zhang H (2018). Inhibition of Myeloperoxidase by N-Acetyl Lysyltyrosylcysteine Amide Reduces Oxidative Stress-Mediated Inflammation, Neuronal Damage, and Neural Stem Cell Injury in a Murine Model of Stroke. J Pharmacol Exp Ther, 364:311-322.
Cai M, Guo YX, Wang SQ, Wei HD, Sun SS, Zhao GC, et al. (2017). Tanshinone IIA Elicits Neuroprotective Effect Through Activating the Nuclear Factor Erythroid 2-Related Factor-Dependent Antioxidant Response. Rejuvenation Research, 20:286-297.
Dou Z, Rong X, Zhao E, Zhang L, Lv Y (2019). Neuroprotection of Resveratrol Against Focal Cerebral Ischemia/Reperfusion Injury in Mice Through a Mechanism Targeting Gut-Brain Axis. Cell Mol Neurobiol, 39:883-898.
Yuen CM, Yeh KH, Wallace CG, Chen KH, Lin HS, Sung PH, et al. (2017). EPO-cyclosporine combination therapy reduced brain infarct area in rat after acute ischemic stroke: role of innate immune-inflammatory response, micro-RNAs and MAPK family signaling pathway. Am J Transl Res, 9:1651-1666.
Zhao Q, Wang X, Chen A, Cheng X, Zhang G, Sun J, et al. (2018). Rhein protects against cerebral ischemic/reperfusioninduced oxidative stress and apoptosis in rats. Int J Mol Med, 41:2802-2812.
Qian H, Ding X, Zhang J, Mao F, Sun Z, Jia H, et al. (2017). Cancer stemness and metastatic potential of the novel tumor cell line K3: an inner mutated cell of bone marrow-derived mesenchymal stem cells. Oncotarget.
Xia D, Zhang Z, Zhao Y (2018). Acteoside Attenuates Oxidative Stress and Neuronal Apoptosis in Rats with Focal Cerebral Ischemia-Reperfusion Injury. Biol Pharm Bull, 41:1645-1651.
Meng X, Xie W, Xu Q, Liang T, Xu X, Sun G, et al. (2018). Neuroprotective Effects of Radix Scrophulariae on Cerebral Ischemia and Reperfusion Injury via MAPK Pathways. Molecules, 23.
Tsai YR, Chang CF, Lai JH, Wu JC, Chen YH, Kang SJ, et al. (2018). Pomalidomide Ameliorates H(2)O(2)-Induced Oxidative Stress Injury and Cell Death in Rat Primary Cortical Neuronal Cultures by Inducing Anti-Oxidative and Anti-Apoptosis Effects. Int J Mol Sci, 19.
Sun J, Ling ZX, Wang FY, Chen WQ, Li HX, Jin JT, et al. (2016). Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis. Neuroscience Letters, 613:30-35.
Wang BD, Guo H, Li X, Yue L, Liu HX, Zhao L, et al. (2018). Adiponectin Attenuates Oxygen-Glucose Deprivation-Induced Mitochondrial Oxidative Injury and Apoptosis in Hippocampal HT22 Cells via the JAK2/STAT3 Pathway. Cell Transplantation, 27:1731-1743.
Xu Y, Wang Y, Wang G, Ye X, Zhang J, Cao G, et al. (2017). YiQiFuMai Powder Injection Protects against Ischemic Stroke via Inhibiting Neuronal Apoptosis and PKCdelta/Drp1-Mediated Excessive Mitochondrial Fission. Oxid Med Cell Longev, 2017:1832093.
Nan W, Zhonghang X, Keyan C, Tongtong L, Wanshu G, Zhongxin X (2018). Epigallocatechin-3-Gallate Reduces Neuronal Apoptosis in Rats after Middle Cerebral Artery Occlusion Injury via PI3K/AKT/eNOS Signaling Pathway. Biomed Res Int, 2018:6473580.
Raghavan A, Shah ZA (2015). Withania somnifera Improves Ischemic Stroke Outcomes by Attenuating PARP1-AIF-Mediated Caspase-Independent Apoptosis. Mol Neurobiol, 52:1093-1105.
Shen K, Wang Y, Zhang Y, Zhou H, Song Y, Cao Z, et al. (2015). Cocktail of Four Active Components Derived from Sheng Mai San Inhibits Hydrogen Peroxide-Induced PC12 Cell Apoptosis Linked with the Caspase-3/ROCK1/MLC Pathway. Rejuvenation Res, 18:517-527.
Xu XH, Li GL, Wang BA, Qin Y, Bai SR, Rong J, et al. (2015). Diallyl trisufide protects against oxygen glucose deprivation -induced apoptosis by scavenging free radicals via the PI3K/Akt -mediated Nrf2/HO-1 signaling pathway in B35 neural cells. Brain Res, 1614:38-50.
Zhang K, Tu M, Gao W, Cai X, Song F, Chen Z, et al. (2019). Hollow Prussian Blue Nanozymes Drive Neuroprotection against Ischemic Stroke via Attenuating Oxidative Stress, Counteracting Inflammation, and Suppressing Cell Apoptosis. Nano Lett, 19:2812-2823.
Li C, Wang X, Cheng F, Du X, Yan J, Zhai C, et al. (2019). Geniposide protects against hypoxia/reperfusion-induced blood-brain barrier impairment by increasing tight junction protein expression and decreasing inflammation, oxidative stress, and apoptosis in an in vitro system. Eur J Pharmacol, 854:224-231.
Li W, Suwanwela NC, Patumraj S (2016). Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R. Microvasc Res, 106:117-127.
Wicha P, Tocharus J, Janyou A, Jittiwat J, Changtam C, Suksamrarn A, et al. (2017). Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model. PLoS One, 12:e0189211.
Dai SH, Chen T, Li X, Yue KY, Luo P, Yang LK, et al. (2017). Sirt3 confers protection against neuronal ischemia by inducing autophagy: Involvement of the AMPK-mTOR pathway. Free Radic Biol Med, 108:345-353.
Wang P, Xu TY, Wei K, Guan YF, Wang X, Xu H, et al. (2014). ARRB1/beta-arrestin-1 mediates neuroprotection through coordination of BECN1-dependent autophagy in cerebral ischemia. Autophagy, 10:1535-1548.
Jiang J, Dai J, Cui H (2018). Vitexin reverses the autophagy dysfunction to attenuate MCAO-induced cerebral ischemic stroke via mTOR/Ulk1 pathway. Biomed Pharmacother, 99:583-590.
Wang M, Li YJ, Ding Y, Zhang HN, Sun T, Zhang K, et al. (2016). Silibinin Prevents Autophagic Cell Death upon Oxidative Stress in Cortical Neurons and Cerebral Ischemia-Reperfusion Injury. Molecular Neurobiology, 53:932-943.
Zhao Y, Huang G, Chen S, Gou Y, Dong Z, Zhang X (2016). Folic acid deficiency increases brain cell injury via autophagy enhancement after focal cerebral ischemia. J Nutr Biochem, 38:41-49.
Chiu BY, Chang CP, Lin JW, Yu JS, Liu WP, Hsu YC, et al. (2014). Beneficial effect of astragalosides on stroke condition using PC12 cells under oxygen glucose deprivation and reperfusion. Cell Mol Neurobiol, 34:825-837.
Dai Y, Zhang H, Zhang J, Yan M (2018). Isoquercetin attenuates oxidative stress and neuronal apoptosis after ischemia/reperfusion injury via Nrf2-mediated inhibition of the NOX4/ROS/NF-kappaB pathway. Chem Biol Interact, 284:32-40.
Wang CP, Shi YW, Tang M, Zhang XC, Gu Y, Liang XM, et al. (2017). Isoquercetin Ameliorates Cerebral Impairment in Focal Ischemia Through Anti-Oxidative, Anti-Inflammatory, and Anti-Apoptotic Effects in Primary Culture of Rat Hippocampal Neurons and Hippocampal CA1 Region of Rats. Mol Neurobiol, 54:2126-2142.
Fu B, Zeng Q, Zhang Z, Qian M, Chen J, Dong W, et al. (2019). Epicatechin Gallate Protects HBMVECs from Ischemia/Reperfusion Injury through Ameliorating Apoptosis and Autophagy and Promoting Neovascularization. Oxid Med Cell Longev, 2019:7824684.
Altermann CDC, Souza MA, Schimidt HL, Izaguirry AP, Martins A, Garcia A, et al. (2017). Short-term green tea supplementation prevents recognition memory deficits and ameliorates hippocampal oxidative stress induced by different stroke models in rats. Brain Res Bull, 131:78-84.
Sosa PM, de Souza MA, Mello-Carpes PB (2018). Green Tea and Red Tea from Camellia sinensis Partially Prevented the Motor Deficits and Striatal Oxidative Damage Induced by Hemorrhagic Stroke in Rats. Neural Plast, 2018:5158724.
Alhadidi Q, Nash KM, Alaqel S, Sayeed MSB, Shah ZA (2018). Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice. Neuroscience, 383:33-45.
Zhang P, Wang T, Zhang D, Zhang Z, Yuan S, Zhang J, et al. (2019). Exploration of MST1-Mediated Secondary Brain Injury Induced by Intracerebral Hemorrhage in Rats via Hippo Signaling Pathway. Transl Stroke Res.
Huang J, Jiang Q (2019). Dexmedetomidine Protects Against Neurological Dysfunction in a Mouse Intracerebral Hemorrhage Model by Inhibiting Mitochondrial Dysfunction-Derived Oxidative Stress. J Stroke Cerebrovasc Dis, 28:1281-1289.
Shi J, Wu G, Zou X, Jiang K (2017). Oleuropein protects intracerebral hemorrhage-induced disruption of blood-brain barrier through alleviation of oxidative stress. Pharmacol Rep, 69:1206-1212.
Wang S, Li D, Huang C, Wan Y, Wang J, Zan X, et al. (2018). Overexpression of adiponectin alleviates intracerebral hemorrhage-induced brain injury in rats via suppression of oxidative stress. Neurosci Lett, 681:110-116.
Zeng J, Chen Y, Ding R, Feng L, Fu Z, Yang S, et al. (2017). Isoliquiritigenin alleviates early brain injury after experimental intracerebral hemorrhage via suppressing ROS- and/or NF-kappaB-mediated NLRP3 inflammasome activation by promoting Nrf2 antioxidant pathway. J Neuroinflammation, 14:119.
Zheng J, Shi L, Liang F, Xu W, Li T, Gao L, et al. (2018). Sirt3 Ameliorates Oxidative Stress and Mitochondrial Dysfunction After Intracerebral Hemorrhage in Diabetic Rats. Front Neurosci, 12:414.
Xu W, Li T, Gao L, Lenahan C, Zheng J, Yan J, et al. (2019). Sodium Benzoate Attenuates Secondary Brain Injury by Inhibiting Neuronal Apoptosis and Reducing Mitochondria-Mediated Oxidative Stress in a Rat Model of Intracerebral Hemorrhage: Possible Involvement of DJ-1/Akt/IKK/NFkappaB Pathway. Front Mol Neurosci, 12:105.
Xie RX, Li DW, Liu XC, Yang MF, Fang J, Sun BL, et al. (2017). Carnosine Attenuates Brain Oxidative Stress and Apoptosis After Intracerebral Hemorrhage in Rats. Neurochem Res, 42:541-551.
Qi B, Hu L, Zhu L, Shang L, Wang X, Liu N, et al. (2017). Metformin Attenuates Neurological Deficit after Intracerebral Hemorrhage by Inhibiting Apoptosis, Oxidative Stress and Neuroinflammation in Rats. Neurochem Res, 42:2912-2920.
Wei N, Wei Y, Li B, Pang L (2017). Baicalein Promotes Neuronal and Behavioral Recovery After Intracerebral Hemorrhage Via Suppressing Apoptosis, Oxidative Stress and Neuroinflammation. Neurochem Res, 42:1345-1353.
Choi KS, Kim HJ, Do SH, Hwang SJ, Yi HJ (2018). Neuroprotective effects of hydrogen inhalation in an experimental rat intracerebral hemorrhage model. Brain Res Bull, 142:122-128.
Xi Z, Hu X, Chen X, Yang Y, Ren J, Wang B, et al. (2019). Protocatechuic acid exerts protective effects via suppression of the P38/JNK- NF-kappaB signalling pathway in an experimental mouse model of intracerebral haemorrhage. Eur J Pharmacol, 854:128-138.
Karuppagounder SS, Alim I, Khim SJ, Bourassa MW, Sleiman SF, John R, et al. (2016). Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models. Sci Transl Med, 8:328ra329.
Liu Y, Qiu J, Wang Z, You W, Wu L, Ji C, et al. (2015). Dimethylfumarate alleviates early brain injury and secondary cognitive deficits after experimental subarachnoid hemorrhage via activation of Keap1-Nrf2-ARE system. J Neurosurg, 123:915-923.
Erdi F, Keskin F, Esen H, Kaya B, Feyzioglu B, Kilinc I, et al. (2016). Telmisartan ameliorates oxidative stress and subarachnoid haemorrhage-induced cerebral vasospasm. Neurological Research, 38:224-231.
Aladag MA, Turkoz Y, Parlakpinar H, Gul M (2017). Nebivolol attenuates cerebral vasospasm both by increasing endothelial nitric oxide and by decreasing oxidative stress in an experimental subarachnoid haemorrhage. British Journal of Neurosurgery, 31:439-445.
Cai J, Xu D, Bai X, Pan R, Wang B, Sun S, et al. (2017). Curcumin mitigates cerebral vasospasm and early brain injury following subarachnoid hemorrhage via inhibiting cerebral inflammation. Brain Behav, 7:e00790.
Liu H, Zhao L, Yue L, Wang B, Li X, Guo H, et al. (2017). Pterostilbene Attenuates Early Brain Injury Following Subarachnoid Hemorrhage via Inhibition of the NLRP3 Inflammasome and Nox2-Related Oxidative Stress. Mol Neurobiol, 54:5928-5940.
Han Y, Zhang T, Su J, Zhao Y, ChenchenWang, et al. (2017). Apigenin attenuates oxidative stress and neuronal apoptosis in early brain injury following subarachnoid hemorrhage. J Clin Neurosci, 40:157-162.
Lu Y, Zhang XS, Zhou XM, Gao YY, Chen CL, Liu JP, et al. (2019). Peroxiredoxin 1/2 protects brain against H2O2-induced apoptosis after subarachnoid hemorrhage. FASEB J, 33:3051-3062.
Zhang T, Wu P, Zhang JH, Li Y, Xu S, Wang C, et al. (2018). Docosahexaenoic Acid Alleviates Oxidative Stress-Based Apoptosis Via Improving Mitochondrial Dynamics in Early Brain Injury After Subarachnoid Hemorrhage. Cell Mol Neurobiol, 38:1413-1423.
Cui Y, Duan X, Li H, Dang B, Yin J, Wang Y, et al. (2016). Hydrogen Sulfide Ameliorates Early Brain Injury Following Subarachnoid Hemorrhage in Rats. Mol Neurobiol, 53:3646-3657.
Zhang ZY, Yang MF, Wang T, Li DW, Liu YL, Zhang JH, et al. (2015). Cysteamine alleviates early brain injury via reducing oxidative stress and apoptosis in a rat experimental subarachnoid hemorrhage model. Cell Mol Neurobiol, 35:543-553.
Wang X, Li S, Ma J, Wang C, Chen A, Xin Z, et al. (2019). Effect of Gastrodin on Early Brain Injury and Neurological Outcome After Subarachnoid Hemorrhage in Rats. Neurosci Bull, 35:461-470.
Cai J, Cao S, Chen J, Yan F, Chen G, Dai Y (2015). Progesterone alleviates acute brain injury via reducing apoptosis and oxidative stress in a rat experimental subarachnoid hemorrhage model. Neurosci Lett, 600:238-243.
Mo J, Enkhjargal B, Travis ZD, Zhou K, Wu P, Zhang G, et al. (2019). AVE 0991 attenuates oxidative stress and neuronal apoptosis via Mas/PKA/CREB/UCP-2 pathway after subarachnoid hemorrhage in rats. Redox Biol, 20:75-86.
Huang CY, Wang LC, Wang HK, Pan CH, Cheng YY, Shan YS, et al. (2015). Memantine alleviates brain injury and neurobehavioral deficits after experimental subarachnoid hemorrhage. Mol Neurobiol, 51:1038-1052.
Zhang X, Wu Q, Lu Y, Wan J, Dai H, Zhou X, et al. (2018). Cerebroprotection by salvianolic acid B after experimental subarachnoid hemorrhage occurs via Nrf2- and SIRT1-dependent pathways. Free Radic Biol Med, 124:504-516.
Zhang XS, Wu Q, Wu LY, Ye ZN, Jiang TW, Li W, et al. (2016). Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats. Cell Death Dis, 7:e2416.
Gu X, Zheng C, Zheng Q, Chen S, Li W, Shang Z, et al. (2017). Salvianolic acid A attenuates early brain injury after subarachnoid hemorrhage in rats by regulating ERK/P38/Nrf2 signaling. Am J Transl Res, 9:5643-5652.
Shao J, Wu Q, Lv SY, Zhou XM, Zhang XS, Wen LL, et al. (2019). Allicin attenuates early brain injury after experimental subarachnoid hemorrhage in rats. J Clin Neurosci, 63:202-208.
Zhang T, Wu P, Budbazar E, Zhu Q, Sun C, Mo J, et al. (2019). Mitophagy Reduces Oxidative Stress Via Keap1 (Kelch-Like Epichlorohydrin-Associated Protein 1)/Nrf2 (Nuclear Factor-E2-Related Factor 2)/PHB2 (Prohibitin 2) Pathway After Subarachnoid Hemorrhage in Rats. Stroke, 50:978-988.
Chen J, Wang L, Wu C, Hu Q, Gu C, Yan F, et al. (2014). Melatonin-enhanced autophagy protects against neural apoptosis via a mitochondrial pathway in early brain injury following a subarachnoid hemorrhage. J Pineal Res, 56:12-19.
Huang X, Xiaokaiti Y, Yang J, Pan J, Li Z, Luria V, et al. (2018). Inhibition of phosphodiesterase 2 reverses gp91phox oxidase-mediated depression- and anxiety-like behavior. Neuropharmacology, 143:176-185.
Heck SO, Zborowski VA, Quines CB, Nogueira CW (2019). 4,4'-Dichlorodiphenyl diselenide reverses a depressive-like phenotype, modulates prefrontal cortical oxidative stress and dysregulated glutamatergic neurotransmission induced by subchronic dexamethasone exposure to mice. J Psychiatr Res, 116:61-68.
Bukharaeva E, Shakirzyanova A, Khuzakhmetova V, Sitdikova G, Giniatullin R (2015). Homocysteine aggravates ROS-induced depression of transmitter release from motor nerve terminals: potential mechanism of peripheral impairment in motor neuron diseases associated with hyperhomocysteinemia. Front Cell Neurosci, 9:391.
Sepehrmanesh Z, Kolahdooz F, Abedi F, Mazroii N, Assarian A, Asemi Z, et al. (2016). Vitamin D Supplementation Affects the Beck Depression Inventory, Insulin Resistance, and Biomarkers of Oxidative Stress in Patients with Major Depressive Disorder: A Randomized, Controlled Clinical Trial. J Nutr, 146:243-248.
Jiang CY, Qin XY, Yuan MM, Lu GJ, Cheng Y (2018). 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside Reverses Stress-Induced Depression via Inflammatory and Oxidative Stress Pathways. Oxid Med Cell Longev, 2018:9501427.
Athira KV, Madhana RM, Chandran JSI, Lahkar M, Sinha S, Naidu VGM (2018). Antidepressant activity of vorinostat is associated with amelioration of oxidative stress and inflammation in a corticosterone-induced chronic stress model in mice. Behavioural Brain Research, 344:73-84.
Bansal Y, Singh R, Saroj P, Sodhi RK, Kuhad A (2018). Naringenin protects against oxido-inflammatory aberrations and altered tryptophan metabolism in olfactory bulbectomized-mice model of depression. Toxicol Appl Pharmacol, 355:257-268.
Umukoro S, Kalejaye HA, Ben-Azu B, Ajayi AM (2018). Naringenin attenuates behavioral derangements induced by social defeat stress in mice via inhibition of acetylcholinesterase activity, oxidative stress and release of pro-inflammatory cytokines. Biomed Pharmacother, 105:714-723.
Zhao XJ, Zhao Z, Yang DD, Cao LL, Zhang L, Ji J, et al. (2017). Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus. Brain Res Bull, 130:146-155.
Thakare VN, Aswar MK, Kulkarni YP, Patil RR, Patel BM (2017). Silymarin ameliorates experimentally induced depressive like behavior in rats: Involvement of hippocampal BDNF signaling, inflammatory cytokines and oxidative stress response. Physiol Behav, 179:401-410.
Chen WJ, Du JK, Hu X, Yu Q, Li DX, Wang CN, et al. (2017). Protective effects of resveratrol on mitochondrial function in the hippocampus improves inflammation-induced depressive-like behavior. Physiol Behav, 182:54-61.
Sulakhiya K, Kumar P, Jangra A, Dwivedi S, Hazarika NK, Baruah CC, et al. (2014). Honokiol abrogates lipopolysaccharide-induced depressive like behavior by impeding neuroinflammation and oxido-nitrosative stress in mice. Eur J Pharmacol, 744:124-131.
Weckmann K, Deery MJ, Howard JA, Feret R, Asara JM, Dethloff F, et al. (2017). Ketamine's antidepressant effect is mediated by energy metabolism and antioxidant defense system. Scientific Reports, 7.
Berkiks I, Benmhammed H, Mesfioui A, Ouichou A, El Hasnaoui A, Mouden S, et al. (2018). Postnatal melatonin treatment protects against affective disorders induced by early-life immune stimulation by reducing the microglia cell activation and oxidative stress. Int J Neurosci, 128:495-504.
Wang Y, Zhao S, Liu X, Zheng Y, Li L, Meng S (2018). Oxytocin improves animal behaviors and ameliorates oxidative stress and inflammation in autistic mice. Biomed Pharmacother, 107:262-269.
Ben Saad H, Kharrat N, Driss D, Gargouri M, Marrakchi R, Jammoussi K, et al. (2017). Effects of vanillin on potassium bromate-induced neurotoxicity in adult mice: impact on behavior, oxidative stress, genes expression, inflammation and fatty acid composition. Arch Physiol Biochem, 123:165-174.
Khalili M, Alavi M, Esmaeil-Jamaat E, Baluchnejadmojarad T, Roghani M (2018). Trigonelline mitigates lipopolysaccharide-induced learning and memory impairment in the rat due to its anti-oxidative and anti-inflammatory effect. Int Immunopharmacol, 61:355-362.
Mehta V, Parashar A, Udayabanu M (2017). Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress. Physiol Behav, 171:69-78.
Herbet M, Izdebska M, Pidtkowska-Chmiel I, Gawronska-Grzywacz M, Natorska-Chomicka D, Pawlowski K, et al. (2018). alpha-Tocopherol Ameliorates Redox Equilibrium and Reduces Inflammatory Response Caused by Chronic Variable Stress. Biomed Research International.
Zhong J, Li G, Xu H, Wang Y, Shi M (2019). Baicalin ameliorates chronic mild stress-induced depression-like behaviors in mice and attenuates inflammatory cytokines and oxidative stress. Braz J Med Biol Res, 52:e8434.
Casaril AM, Domingues M, Bampi SR, de Andrade Lourenco D, Padilha NB, Lenardao EJ, et al. (2019). The selenium-containing compound 3-((4-chlorophenyl)selanyl)-1-methyl-1H-indole reverses depressive-like behavior induced by acute restraint stress in mice: modulation of oxido-nitrosative stress and inflammatory pathway. Psychopharmacology (Berl).
Abdallah CG, De Feyter HM, Averill LA, Jiang L, Averill CL, Chowdhury GMI, et al. (2018). The effects of ketamine on prefrontal glutamate neurotransmission in healthy and depressed subjects. Neuropsychopharmacology, 43:2154-2160.
Du RH, Wu FF, Lu M, Shu XD, Ding JH, Wu G, et al. (2016). Uncoupling protein 2 modulation of the NLRP3 inflammasome in astrocytes and its implications in depression. Redox Biol, 9:178-187.
Yang M, Dang R, Xu P, Guo Y, Han W, Liao D, et al. (2018). Dl-3-n-Butylphthalide improves lipopolysaccharide-induced depressive-like behavior in rats: involvement of Nrf2 and NF-kappaB pathways. Psychopharmacology (Berl), 235:2573-2585.
El-Naga RN, Ahmed HI, Abd Al Haleem EN (2014). Effects of indole-3-carbinol on clonidine-induced neurotoxicity in rats: Impact on oxidative stress, inflammation, apoptosis and monoamine levels. Neurotoxicology, 44:48-57.
Shal B, Khan A, Naveed M, Ullah Khan N, Ihsan Ul H, S DA, et al. (2019). Effect of 25-methoxy hispidol A isolated from Poncirus trifoliate against bacteria-induced anxiety and depression by targeting neuroinflammation, oxidative stress and apoptosis in mice. Biomed Pharmacother, 111:209-223.
Gao W, Wang W, Liu G, Zhang J, Yang J, Deng Z (2019). Allicin attenuated chronic social defeat stress induced depressive-like behaviors through suppression of NLRP3 inflammasome. Metab Brain Dis, 34:319-329.
Li X, Wu T, Yu Z, Li T, Zhang J, Zhang Z, et al. (2018). Apocynum venetum leaf extract reverses depressive-like behaviors in chronically stressed rats by inhibiting oxidative stress and apoptosis. Biomed Pharmacother, 100:394-406.
Tang ZY, Li M, Zhang XW, Hou WS (2016). Dietary flavonoid intake and the risk of stroke: a dose-response meta-analysis of prospective cohort studies. Bmj Open, 6.
Bao D, Wang J, Pang X, Liu H (2017). Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells. Molecules, 22.
Alam F, Saqib QN, Ashraf M (2017). Gaultheria trichophylla (Royle): a source of minerals and biologically active molecules, its antioxidant and anti-lipoxygenase activities. BMC Complement Altern Med, 17:3.
Carradori S, Gidaro MC, Petzer A, Costa G, Guglielmi P, Chimenti P, et al. (2016). Inhibition of Human Monoamine Oxidase: Biological and Molecular Modeling Studies on Selected Natural Flavonoids. J Agric Food Chem, 64:9004-9011.
Chang SC, Cassidy A, Willett WC, Rimm EB, O'Reilly EJ, Okereke OI (2016). Dietary flavonoid intake and risk of incident depression in midlife and older women. Am J Clin Nutr, 104:704-714.
Chamorro A, Amaro S, Castellanos M, Segura T, Arenillas J, Marti-Fabregas J, et al. (2014). Safety and efficacy of uric acid in patients with acute stroke (URICO-ICTUS): a randomised, double-blind phase 2b/3 trial. Lancet Neurol, 13:453-460.
Llull L, Laredo C, Renu A, Perez B, Vila E, Obach V, et al. (2015). Uric Acid Therapy Improves Clinical Outcome in Women With Acute Ischemic Stroke. Stroke, 46:2162-2167.
Amaro S, Llull L, Renu A, Laredo C, Perez B, Vila E, et al. (2015). Uric acid improves glucose-driven oxidative stress in human ischemic stroke. Ann Neurol, 77:775-783.
Wium-Andersen MK, Kobylecki CJ, Afzal S, Nordestgaard BG (2017). Association between the antioxidant uric acid and depression and antidepressant medication use in 96 989 individuals. Acta Psychiatrica Scandinavica, 136:424-433.
Bartoli F, Trotta G, Crocamo C, Malerba MR, Clerici M, Carra G (2018). Antioxidant uric acid in treated and untreated subjects with major depressive disorder: a meta-analysis and meta-regression. Eur Arch Psychiatry Clin Neurosci, 268:119-127.
Aly H, Elmandy H, El-Dib M, Rowisha M, Awny M, El-Gohary T, et al. (2015). Melatonin use for neuroprotection in perinatal asphyxia: a randomized controlled pilot study. Journal of Perinatology, 35:186-191.
Targum SD, Wedel PC, Fava M (2015). Changes in cognitive symptoms after a buspirone-melatonin combination treatment for Major Depressive Disorder. J Psychiatr Res, 68:392-396.
Villa RF, Ferrari F, Moretti A (2018). Post-stroke depression: Mechanisms and pharmacological treatment. Pharmacol Ther, 184:131-144.
Collaboration FT (2019). Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, double-blind, randomised, controlled trial. Lancet, 393:265-274.
Sun Y, Liang Y, Jiao Y, Lin J, Qu H, Xu J, et al. (2017). Comparative efficacy and acceptability of antidepressant treatment in poststroke depression: a multiple-treatments meta-analysis. BMJ Open, 7:e016499.
Chollet F, Tardy J, Albucher JF, Thalamas C, Berard E, Lamy C, et al. (2011). Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. Lancet Neurol, 10:123-130.
Kim JS (2017). Management of post-stroke mood and emotional disturbances. Expert Rev Neurother, 17:1179-1188.
Kim JS, Lee EJ, Chang DI, Park JH, Ahn SH, Cha JK, et al. (2017). Efficacy of early administration of escitalopram on depressive and emotional symptoms and neurological dysfunction after stroke: a multicentre, double-blind, randomised, placebo-controlled study. Lancet Psychiatry, 4:33-41.
Robinson RG, Jorge RE, Moser DJ, Acion L, Solodkin A, Small SL, et al. (2008). Escitalopram and problem-solving therapy for prevention of poststroke depression: a randomized controlled trial. JAMA, 299:2391-2400.
Savadi Oskouie D, Sharifipour E, Sadeghi Bazargani H, Hashemilar M, Nikanfar M, Ghazanfari Amlashi S, et al. (2017). Efficacy of Citalopram on Acute Ischemic Stroke Outcome: A Randomized Clinical Trial. Neurorehabil Neural Repair, 31:638-647.
Kraglund KL, Mortensen JK, Grove EL, Johnsen SP, Andersen G (2015). TALOS: a multicenter, randomized, double-blind, placebo-controlled trial to test the effects of citalopram in patients with acute stroke. Int J Stroke, 10:985-987.
Mortensen JK, Larsson H, Johnsen SP, Andersen G (2014). Impact of prestroke selective serotonin reuptake inhibitor treatment on stroke severity and mortality. Stroke, 45:2121-2123.
Tsai CS, Wu CL, Chou SY, Tsang HY, Hung TH, Su JA (2011). Prevention of poststroke depression with milnacipran in patients with acute ischemic stroke: a double-blind randomized placebo-controlled trial. Int Clin Psychopharmacol, 26:263-267.
Ferro JM, Caeiro L, Figueira ML (2016). Neuropsychiatric sequelae of stroke. Nat Rev Neurol, 12:269-280.
Guiraud V, Gallarda T, Calvet D, Turc G, Oppenheim C, Rouillon F, et al. (2016). Depression predictors within six months of ischemic stroke: The DEPRESS Study. International Journal of Stroke, 11:519-525.
Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV (2019). Blood-Brain Barrier: From Physiology to Disease and Back. Physiol Rev, 99:21-78.
Tang Z, Li M, Zhang X, Hou W (2016). Dietary flavonoid intake and the risk of stroke: a dose-response meta-analysis of prospective cohort studies. BMJ Open, 6:e008680.
De Crescenzo F, Lennox A, Gibson JC, Cordey JH, Stockton S, Cowen PJ, et al. (2017). Melatonin as a treatment for mood disorders: a systematic review. Acta Psychiatr Scand, 136:549-558.
Valko M, Leibfritz D, Moncol J, Cronin MTD, Mazur M, Telser J (2007). Free radicals and antioxidants in normal physiological functions and human disease. International Journal of Biochemistry & Cell Biology, 39:44-84.
Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK (2018). Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ Res, 122:877-902.
Serrander L, Cartier L, Bedard K, Banfi B, Lardy B, Plastre O, et al. (2007). NOX4 activity is determined by mRNA levels and reveals a unique pattern of ROS generation. Biochemical Journal, 406:105-114.
Saso L, Firuzi O (2014). Pharmacological applications of antioxidants: lights and shadows. Curr Drug Targets, 15:1177-1199.
Khey KMW, Huard A, Mahmoud SH (2019). Inflammatory Pathways Following Subarachnoid Hemorrhage. Cell Mol Neurobiol.