Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
 
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and disease    2021, Vol. 12 Issue (1) : 72-92     DOI: 10.14336/AD.2020.0406
Orginal Article |
Brain-derived CCR5 Contributes to Neuroprotection and Brain Repair after Experimental Stroke
Suning Ping, Xuecheng Qiu, Michele Kyle, Li-Ru Zhao*
Department of Neurosurgery, State University of New York Upstate Medical University, New York, USA
Download: PDF(2506 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    
Abstract  

Chemokine (C-C motif) receptor 5 (CCR5) is expressed not only in the immune cells but also in cerebral cells such as neurons, glia, and vascular cells. Stroke triggers high expression of CCR5 in the brain. However, the role of CCR5 in stroke remains unclear. In this study, using bone marrow chimeras we have determined the involvement of brain-derived or bone marrow-derived CCR5 in neuroprotection and brain repair after experimental stroke. CCR5-/- mice that received either wild-type (WT) or CCR5-/- bone marrow transplantation showed larger infarction sizes than the WT mice that received either WT or CCR5-/- bone marrow transplantation in both the acute (48h) and subacute (2 months) phases after cerebral cortical ischemia, suggesting that the lack of CCR5 in the brain leads to severe brain damage after stroke. However, the lack of CCR5 in the bone marrow-derived cells did not affect infarction size. The impairments of somatosensory-motor function and motor coordination were exacerbated in the mice lacking CCR5 in the brain. At 2 months post-stroke, increased degenerative neurons, decreased dendrites and synapses, decreased Iba1+ microglia/ macrophages, reduced myelination and CNPase+ oligodendrocytes in the peri-infarct cortex were observed in the mice lacking CCR5 in the brain. These pathological changes are significantly correlated with the increased infarction size and exacerbated neurological deficits. These data suggest that brain-derived CCR5 plays a key role in neuroprotection and brain repair in the subacute phase of stroke. This study reveals a novel role of CCR5 in stroke, which sheds new light on post-stroke pathomechanism.

Keywords CCR5      stroke      neuroprotection      neurological deficits      subacute phase     
Corresponding Authors: Zhao Li-Ru   
About author:

these authors contributed equally to this work.

Just Accepted Date: 10 April 2020   Issue Date: 11 January 2021
Service
E-mail this article
E-mail Alert
RSS
Articles by authors
Ping Suning
Qiu Xuecheng
Kyle Michele
Zhao Li-Ru
Cite this article:   
Ping Suning,Qiu Xuecheng,Kyle Michele, et al. Brain-derived CCR5 Contributes to Neuroprotection and Brain Repair after Experimental Stroke[J]. Aging and disease, 2021, 12(1): 72-92.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2020.0406     OR
Figure 1.  Experimental flowchart and groups. (A) A schematic diagram shows the flowchart of the experiment. Three-month-old wild type (WT) and CCR5-/- mice received irradiation and bone marrow transplantation. After one month-bone marrow reconstruction, mice were subjected to middle cerebral artery occlusion (MCAO) for induction of focal cerebral ischemia. Triphenyl tetrazolium chloride (TTC) staining was performed 48h after MCAO to measure the infarction size (N = 6/group). Two weeks after MCAO, behavioral tests were performed to evaluate neurological deficits (N=9/group). Two months after MCAO, mice were sacrificed for immunohistochemistry (N=7-8/group). (B) A table shows the information about the four experimental groups of chimeric mice. RwtDwt: WT mice received bone marrow transplantation (BMT) from the bone marrow donor of WT mice. RwtDccr5: WT mice received BMT from the bone marrow donor of CCR5-/- mice. Rccr5Dwt: CCR5-/- mice received BMT from the bone marrow donor of WT mice. Rccr5Dccr5: CCR5-/- mice received BMT from the bone marrow donor of CCR5-/- mice.
Figure 2.  Infarct volume is increased in the mice lacking CCR5 in the brain. (A) Representative images of triphenyl tetrazolium chloride (TTC) staining 48h after middle cerebral artery occlusion (MCAO). (B) Quantification data of infarct volume using TTC staining. (C) Representative images of cresyl violet staining two months after MCAO. A longitudinal notch was made in the left brain to distinguish the contralesional hemisphere from the ipsilesional hemisphere. (D) Quantification data of infarct volume using cresyl violet staining. Mean ± S.E.M. N=6/group. **p<0.01, ***p<0.001. One-way ANOVA with Tukey post hoc test.
Figure 3.  Cerebral cortical ischemia-induced neurological deficits are exacerbated in the mice lacking CCR5 in the brain. (A) Somatosensory-motor function was examined using a tape removal test. Data were collected from three independent trials each day. Mean ± S.E.M. N=9/group. *p<0.05, **p<0.01. One-way ANOVA with Tukey post hoc test. (B) Motor coordination function was examined using a rotarod test. Data were collected from three independent trials each day for five consecutive days. Mean± S.E.M. N=9/group. *p<0.05, **p<0.01; RwtDwt mice vs. Rccr5Dwt mice. &p<0.05, RwtDwt mice vs. Rccr5Dccr5 mice. #p<0.05, RwtDccr5 mice vs. Rccr5Dwt mice. Two-way repeated ANOVA with Fisher’s LSD multiple comparison test.
Figure 4.  Neuronal degeneration in the peri-infarct cortex 2 months after cerebral cortical ischemia. Note that the mice lacking CCR5 in the brain show increased Fluoro-Jade C+ degenerating neurons, reduced MAP2+ dendritic density and decreased PSD-95+ post-synapses in the peri-infarct cortex. (A-D) Representative images show immunofluorescence staining for NeuN in the peri-infarct cortex. (E) Quantification data of NeuN positive neurons in the peri-infarct cortex. (F-I) Representative images show Fluoro-Jade C staining in the peri-infarct cortex. (J) Quantification data of Fluoro-Jade C positive degenerating neurons in the peri-infarct cortex. (K-R) Representative images show MAP2+ dendrites and PSD-95+ post-synapses in the peri-infarct cortical layer 1-3. (S) Schematic diagrams indicate the imaging areas in the cortex. (T-W) Quantification data of MAP2 and PSD-95 positive area in the peri-infarct cortical layer 1 and layer 2/3. Mean± S.E.M. N=7-8/group. *p<0.05, **p<0.01. One-way ANOVA with Tukey post hoc test. N.S.: not significant.
Figure 5.  Inflammatory cells in the peri-infarct cortex 2 months after cerebral cortical ischemia. Note that reduced Iba1+ cells, increased P2RY12+ cells and decreased CD68+ cells in the peri-infarct cortex are seen in the mice lacking CCR5 in the brain (Rccr5Dwt). (A-E) Representative images of immunofluorescence staining for Iba1 in the peri-infarct cortex. (F-J) Representative images of immunofluorescence staining for P2RY12 in the peri-infarct cortex. (K-O) Representative images of immunofluorescence staining for CD68 in the peri-infarct cortex. (P) Schematic diagrams show the imaging areas in the cortex. (Q-S) Quantification data of Iba1, P2RY12 and CD68 positive area in the peri-infarct cortex. Mean± S.E.M. N=7-8/group. *p<0.05, **p<0.01, *** p<0.001. One-way ANOVA with Tukey post hoc test.
Figure 6.  Neuroinflammatory molecule expression in the peri-infarct cortex 2 months after cerebral cortical ischemia. Note that stroke mice show reduced IL-4 expression and increased NOS2 expression in the peri-infarct cortex as compared to the naïve control mice. Stroke mice lacking CCR5 in both the brain and bone marrow show increased NOS2 expression in the peri-infarct cortex (RwtDccr5, Rccr5Dwt, and Rccr5Dccr5 vs. RwtDwt). (A-E) Representative images of immunofluorescence staining for IL-4 in the peri-infarct cortex. (F to J) Representative images of immunofluorescence staining for NOS2 in the peri-infarct cortex. (K) Schematic diagrams indicate the imaging areas in the cortex. (L and M) Quantification data of IL-4 and NOS2 positive area in the peri-infarct cortex. Mean± S.E.M. N=7-8/group. *p<0.05, **p<0.01. One-way ANOVA with Tukey post hoc test.
Figure 7.  Myelination in the peri-infarct cortex 2 months after cerebral cortical ischemia. Note that mice lacking CCR5 in the brain show reduced myelination in the peri-infarct cortex 2 months after cerebral cortical ischemia. (A-D) Representative images of immunofluorescence staining for CNPase in the peri-infarct cortex. (E-H) Representative images of immunofluorescence staining for MBP in the peri-infarct cortex. (I) A schematic diagram indicates the imaging areas in the cortex. (J and K) Quantification data of CNPase and MBP positive areas in the peri-infarct cortex. Mean± S.E.M. N=7-8/group. *p<0.05, **p<0.01. One-way ANOVA with Tukey post hoc test.
Figure 8.  Blood vessel density and astrogliosis in the peri-infarct cortex are not affected by CCR5 deficiency. (A-D) Representative images show Lectin positive blood vessels in the peri-infarct cortex. (E-H) Representative images of immunofluorescence staining for GFAP in the peri-infarct cortex. (I) Schematic diagrams indicate the imaging areas in the cortex. (J and K) Quantification data of Lectin and GFAP positive area in the peri-infarct cortex. Mean ± S.E.M. N=7-8/group. One-way ANOVA with Tukey post hoc test. N.S.: not significant.
[1] Zhao LR, Willing A (2018). Enhancing endogenous capacity to repair a stroke-damaged brain: An evolving field for stroke research. Prog Neurobiol, 163-164:5-26.
[2] Donnan GA, Fisher M, Macleod M, Davis SM (2008). Stroke. Lancet, 371:1612-1623.
[3] Bernheisel CR, Schlaudecker JD, Leopold K (2011). Subacute management of ischemic stroke. Am Fam Physician, 84:1383-1388.
[4] Parsons MW, Li T, Barber PA, Yang Q, Darby DG, Desmond PM, et al. (2000). Combined (1)H MR spectroscopy and diffusion-weighted MRI improves the prediction of stroke outcome. Neurology, 55:498-505.
[5] Kang DW, Latour LL, Chalela JA, Dambrosia JA, Warach S (2004). Early and late recurrence of ischemic lesion on MRI: evidence for a prolonged stroke-prone state? Neurology, 63:2261-2265.
[6] Maraka S, Jiang Q, Jafari-Khouzani K, Li L, Malik S, Hamidian H, et al. (2014). Degree of corticospinal tract damage correlates with motor function after stroke. Ann Clin Transl Neurol, 1:891-899.
[7] Jayaraj RL, Azimullah S, Beiram R, Jalal FY, Rosenberg GA (2019). Neuroinflammation: friend and foe for ischemic stroke. J Neuroinflammation, 16:142.
[8] Cui L, Wang D, McGillis S, Kyle M, Zhao LR (2016). Repairing the Brain by SCF+G-CSF Treatment at 6 Months Postexperimental Stroke: Mechanistic Determination of the Causal Link Between Neurovascular Regeneration and Motor Functional Recovery. ASN Neuro, 8.
[9] Cui L, Duchamp NS, Boston DJ, Ren X, Zhang X, Hu H, et al. (2015). NF-kappaB is involved in brain repair by stem cell factor and granulocyte-colony stimulating factor in chronic stroke. Exp Neurol, 263:17-27.
[10] Liu Y, Popescu M, Longo S, Gao M, Wang D, McGillis S, et al. (2016). Fibrinogen Reduction and Motor Function Improvement by Hematopoietic Growth Factor Treatment in Chronic Stroke in Aged Mice: A Treatment Frequency Study. Cell Transplant, 25:729-734.
[11] Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al. (2005). Effects of non-invasive cortical stimulation on skilled motor function in chronic stroke. Brain, 128:490-499.
[12] Lee YY, Lin KC, Cheng HJ, Wu CY, Hsieh YW, Chen CK (2015). Effects of combining robot-assisted therapy with neuromuscular electrical stimulation on motor impairment, motor and daily function, and quality of life in patients with chronic stroke: a double-blinded randomized controlled trial. J Neuroeng Rehabil, 12:96.
[13] Takeuchi N, Chuma T, Matsuo Y, Watanabe I, Ikoma K (2005). Repetitive transcranial magnetic stimulation of contralesional primary motor cortex improves hand function after stroke. Stroke, 36:2681-2686.
[14] Sorce S, Myburgh R, Krause KH (2011). The chemokine receptor CCR5 in the central nervous system. Prog Neurobiol, 93:297-311.
[15] Li P, Wang L, Zhou Y, Gan Y, Zhu W, Xia Y, et al. (2017). C-C Chemokine Receptor Type 5 (CCR5)-Mediated Docking of Transferred Tregs Protects Against Early Blood-Brain Barrier Disruption After Stroke. J Am Heart Assoc, 6.
[16] Abid S, Marcos E, Parpaleix A, Amsellem V, Breau M, Houssaini A, et al. (2019). CCR2/CCR5-mediated macrophage-smooth muscle cell crosstalk in pulmonary hypertension. Eur Respir J, 54.
[17] Louboutin JP, Strayer DS (2013). Relationship between the chemokine receptor CCR5 and microglia in neurological disorders: consequences of targeting CCR5 on neuroinflammation, neuronal death and regeneration in a model of epilepsy. CNS Neurol Disord Drug Targets, 12:815-829.
[18] Lee YK, Kwak DH, Oh KW, Nam SY, Lee BJ, Yun YW, et al. (2009). CCR5 deficiency induces astrocyte activation, Abeta deposit and impaired memory function. Neurobiol Learn Mem, 92:356-363.
[19] Joy MT, Ben Assayag E, Shabashov-Stone D, Liraz-Zaltsman S, Mazzitelli J, Arenas M, et al. (2019). CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury. Cell, 176:1143-1157.e1113.
[20] Zhang Z, Dong J, Lobe CG, Gong P, Liu J, Liao L (2015). CCR5 facilitates endothelial progenitor cell recruitment and promotes the stabilization of atherosclerotic plaques in ApoE-/- mice. Stem Cell Res Ther, 6:36.
[21] Afonso P, Auclair M, Caron-Debarle M, Capeau J (2017). Impact of CCR5, integrase and protease inhibitors on human endothelial cell function, stress, inflammation and senescence. Antivir Ther, 22:645-657.
[22] Sorce S, Bonnefont J, Julien S, Marq-Lin N, Rodriguez I, Dubois-Dauphin M, et al. (2010). Increased brain damage after ischaemic stroke in mice lacking the chemokine receptor CCR5. Br J Pharmacol, 160:311-321.
[23] Wattananit S, Tornero D, Graubardt N, Memanishvili T, Monni E, Tatarishvili J, et al. (2016). Monocyte-Derived Macrophages Contribute to Spontaneous Long-Term Functional Recovery after Stroke in Mice. J Neurosci, 36:4182-4195.
[24] Fang W, Zhai X, Han D, Xiong X, Wang T, Zeng X, et al. (2018). CCR2-dependent monocytes/macrophages exacerbate acute brain injury but promote functional recovery after ischemic stroke in mice. Theranostics, 8:3530-3543.
[25] Cui L, Murikinati SR, Wang D, Zhang X, Duan WM, Zhao LR (2013). Reestablishing neuronal networks in the aged brain by stem cell factor and granulocyte-colony stimulating factor in a mouse model of chronic stroke. PLoS One, 8:e64684.
[26] Gusel'nikova VV, Korzhevskiy DE (2015). NeuN As a Neuronal Nuclear Antigen and Neuron Differentiation Marker. Acta Naturae, 7:42-47.
[27] Toshkezi G, Kyle M, Longo SL, Chin LS, Zhao LR (2018). Brain repair by hematopoietic growth factors in the subacute phase of traumatic brain injury. J Neurosurg, 129:1286-1294.
[28] Johnson GV, Jope RS (1992). The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration. J Neurosci Res, 33:505-512.
[29] Dehmelt L, Halpain S (2005). The MAP2/Tau family of microtubule-associated proteins. Genome Biol, 6:204.
[30] Soltani MH, Pichardo R, Song Z, Sangha N, Camacho F, Satyamoorthy K, et al. (2005). Microtubule-associated protein 2, a marker of neuronal differentiation, induces mitotic defects, inhibits growth of melanoma cells, and predicts metastatic potential of cutaneous melanoma. Am J Pathol, 166:1841-1850.
[31] Hunt CA, Schenker LJ, Kennedy MB (1996). PSD-95 is associated with the postsynaptic density and not with the presynaptic membrane at forebrain synapses. J Neurosci, 16:1380-1388.
[32] Coley AA, Gao WJ (2018). PSD95: A synaptic protein implicated in schizophrenia or autism? Prog Neuropsychopharmacol Biol Psychiatry, 82:187-194.
[33] Kawabori M, Yenari MA (2015). Inflammatory responses in brain ischemia. Curr Med Chem, 22:1258-1277.
[34] Ohsawa K, Imai Y, Sasaki Y, Kohsaka S (2004). Microglia/macrophage-specific protein Iba1 binds to fimbrin and enhances its actin-bundling activity. J Neurochem, 88:844-856.
[35] Zhu C, Kros JM, van der Weiden M, Zheng P, Cheng C, Mustafa DA (2017). Expression site of P2RY12 in residential microglial cells in astrocytomas correlates with M1 and M2 marker expression and tumor grade. Acta Neuropathol Commun, 5:4.
[36] Shen F, Jiang L, Han F, Degos V, Chen S, Su H (2019). Increased Inflammatory Response in Old Mice is Associated with More Severe Neuronal Injury at the Acute Stage of Ischemic Stroke. Aging Dis, 10:12-22.
[37] Zhao X, Wang H, Sun G, Zhang J, Edwards NJ, Aronowski J (2015). Neuronal Interleukin-4 as a Modulator of Microglial Pathways and Ischemic Brain Damage. J Neurosci, 35:11281-11291.
[38] Lv B, Cheng X, Sharp FR, Ander BP, Liu DZ (2018). MicroRNA-122 Mimic Improves Stroke Outcomes and Indirectly Inhibits NOS2 After Middle Cerebral Artery Occlusion in Rats. Front Neurosci, 12:767.
[39] Lakhani B, Hayward KS, Boyd LA (2017). Hemispheric asymmetry in myelin after stroke is related to motor impairment and function. Neuroimage Clin, 14:344-353.
[40] Jalal FY, Yang Y, Thompson J, Lopez AC, Rosenberg GA (2012). Myelin loss associated with neuroinflammation in hypertensive rats. Stroke, 43:1115-1122.
[41] Hoffmann CJ, Harms U, Rex A, Szulzewsky F, Wolf SA, Grittner U, et al. (2015). Vascular signal transducer and activator of transcription-3 promotes angiogenesis and neuroplasticity long-term after stroke. Circulation, 131:1772-1782.
[42] Liu Z, Chopp M (2016). Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol, 144:103-120.
[43] Tuttle DL, Harrison JK, Anders C, Sleasman JW, Goodenow MM (1998). Expression of CCR5 increases during monocyte differentiation and directly mediates macrophage susceptibility to infection by human immunodeficiency virus type 1. J Virol, 72:4962-4969.
[44] Benakis C, Garcia-Bonilla L, Iadecola C, Anrather J (2014). The role of microglia and myeloid immune cells in acute cerebral ischemia. Front Cell Neurosci, 8:461.
[45] Miro-Mur F, Perez-de-Puig I, Ferrer-Ferrer M, Urra X, Justicia C, Chamorro A, et al. (2016). Immature monocytes recruited to the ischemic mouse brain differentiate into macrophages with features of alternative activation. Brain Behav Immun, 53:18-33.
[46] Wang L, Yu C, Chen H, Qin W, He Y, Fan F, et al. (2010). Dynamic functional reorganization of the motor execution network after stroke. Brain, 133:1224-1238.
[47] Sharma N, Cohen LG (2012). Recovery of motor function after stroke. Dev Psychobiol, 54:254-262.
[48] Carmichael ST (2012). Brain excitability in stroke: the yin and yang of stroke progression. Arch Neurol, 69:161-167.
[49] Tombari D, Loubinoux I, Pariente J, Gerdelat A, Albucher JF, Tardy J, et al. (2004). A longitudinal fMRI study: in recovering and then in clinically stable sub-cortical stroke patients. Neuroimage, 23:827-839.
[50] Brown CE, Li P, Boyd JD, Delaney KR, Murphy TH (2007). Extensive turnover of dendritic spines and vascular remodeling in cortical tissues recovering from stroke. J Neurosci, 27:4101-4109.
[51] Shiotsuki H, Yoshimi K, Shimo Y, Funayama M, Takamatsu Y, Ikeda K, et al. (2010). A rotarod test for evaluation of motor skill learning. J Neurosci Methods, 189:180-185.
[52] Caston J, Jones N, Stelz T (1995). Role of preoperative and postoperative sensorimotor training on restoration of the equilibrium behavior in adult mice following cerebellectomy. Neurobiol Learn Mem, 64:195-202.
[53] Gu SM, Park MH, Yun HM, Han SB, Oh KW, Son DJ, et al. (2016). CCR5 knockout suppresses experimental autoimmune encephalomyelitis in C57BL/6 mice. Oncotarget, 7:15382-15393.
[54] Li T, Zhu J (2019). Entanglement of CCR5 and Alzheimer's Disease. Front Aging Neurosci, 11:209.
[55] Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, et al. (2014). Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci, 17:131-143.
[56] Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, et al. (2006). The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci, 9:1512-1519.
[57] Zrzavy T, Hametner S, Wimmer I, Butovsky O, Weiner HL, Lassmann H (2017). Loss of 'homeostatic' microglia and patterns of their activation in active multiple sclerosis. Brain, 140:1900-1913.
[58] Boer K, Spliet WG, van Rijen PC, Redeker S, Troost D, Aronica E (2006). Evidence of activated microglia in focal cortical dysplasia. J Neuroimmunol, 173:188-195.
[59] Bellver-Landete V, Bretheau F, Mailhot B, Vallieres N, Lessard M, Janelle ME, et al. (2019). Microglia are an essential component of the neuroprotective scar that forms after spinal cord injury. Nat Commun, 10:518.
[60] Imai Y, Kohsaka S (2002). Intracellular signaling in M-CSF-induced microglia activation: role of Iba1. Glia, 40:164-174.
[61] Li B, Gonzalez-Toledo ME, Piao CS, Gu A, Kelley RE, Zhao LR (2011). Stem cell factor and granulocyte colony-stimulating factor reduce beta-amyloid deposits in the brains of APP/PS1 transgenic mice. Alzheimers Res Ther, 3:8.
[62] Garry PS, Ezra M, Rowland MJ, Westbrook J, Pattinson KT (2015). The role of the nitric oxide pathway in brain injury and its treatment--from bench to bedside. Exp Neurol, 263:235-243.
[63] Hartline DK, Colman DR (2007). Rapid conduction and the evolution of giant axons and myelinated fibers. Curr Biol, 17:R29-35.
[64] Stassart RM, Mobius W, Nave KA, Edgar JM (2018). The Axon-Myelin Unit in Development and Degenerative Disease. Front Neurosci, 12:467.
[65] Jia W, Kamen Y, Pivonkova H, Karadottir RT (2019). Neuronal activity-dependent myelin repair after stroke. Neurosci Lett, 703:139-144.
[66] Zhou J, Zhuang J, Li J, Ooi E, Bloom J, Poon C, et al. (2013). Long-term post-stroke changes include myelin loss, specific deficits in sensory and motor behaviors and complex cognitive impairment detected using active place avoidance. PLoS One, 8:e57503.
[67] Hunt JS, Romanelli F (2009). Maraviroc, a CCR5 coreceptor antagonist that blocks entry of human immunodeficiency virus type 1. Pharmacotherapy, 29:295-304.
[68] Peterson LK, Fujinami RS (2007). Inflammation, demyelination, neurodegeneration and neuroprotection in the pathogenesis of multiple sclerosis. J Neuroimmunol, 184:37-44.
[69] Sullivan GM, Mierzwa AJ, Kijpaisalratana N, Tang H, Wang Y, Song SK, et al. (2013). Oligodendrocyte lineage and subventricular zone response to traumatic axonal injury in the corpus callosum. J Neuropathol Exp Neurol, 72:1106-1125.
[70] Mierzwa AJ, Marion CM, Sullivan GM, McDaniel DP, Armstrong RC (2015). Components of myelin damage and repair in the progression of white matter pathology after mild traumatic brain injury. J Neuropathol Exp Neurol, 74:218-232.
[71] Rawji KS, Mishra MK, Yong VW (2016). Regenerative Capacity of Macrophages for Remyelination. Front Cell Dev Biol, 4:47.
[72] Stratton JA, Holmes A, Rosin NL, Sinha S, Vohra M, Burma NE, et al. (2018). Macrophages Regulate Schwann Cell Maturation after Nerve Injury. Cell Rep, 24:2561-2572.e2566.
[1] Supplementary data Download
[1] Qian Chen,Tianyi Xia,Mingyue Zhang,Nengzhi Xia,Jinjin Liu,Yunjun Yang. Radiomics in Stroke Neuroimaging: Techniques, Applications, and Challenges[J]. Aging and disease, 2021, 12(1): 143-154.
[2] Weili Li,Zhifeng Qi,Huining Kang,Xuzhen Qin,Haiqing Song,Xueqin Sui,Yi Ren,Xunming Ji,Qingfeng Ma,Ke Jian Liu. Serum Occludin as a Biomarker to Predict the Severity of Acute Ischemic Stroke, Hemorrhagic Transformation, and Patient Prognosis[J]. Aging and disease, 2020, 11(6): 1395-1406.
[3] Xuan Li,Ya Feng,Xi-Xi Wang,Daniel Truong,Yun-Cheng Wu. The Critical Role of SIRT1 in Parkinson’s Disease: Mechanism and Therapeutic Considerations[J]. Aging and disease, 2020, 11(6): 1608-1622.
[4] Anwen Shao,Danfeng Lin,Lingling Wang,Sheng Tu,Cameron Lenahan,Jianmin Zhang. Oxidative Stress at the Crossroads of Aging, Stroke and Depression[J]. Aging and disease, 2020, 11(6): 1537-1566.
[5] Longfei Wu,Mitchell Huber,Di Wu,Jian Chen,Ming Li,Yuchuan Ding,Xunming Ji. Intra-arterial Cold Saline Infusion in Stroke: Historical Evolution and Future Prospects[J]. Aging and disease, 2020, 11(6): 1527-1536.
[6] Yuanjian Fang,Reng Ren,Hui Shi,Lei Huang,Cameron Lenahan,Qin Lu,Lihui Tang,Yi Huang,Jiping Tang,Jianmin Zhang,John H Zhang. Pituitary Adenylate Cyclase-Activating Polypeptide: A Promising Neuroprotective Peptide in Stroke[J]. Aging and disease, 2020, 11(6): 1496-1512.
[7] Bharathi Hattiangady,Ramkumar Kuruba,Bing Shuai,Remedios Grier,Ashok K Shetty. Hippocampal Neural Stem Cell Grafting after Status Epilepticus Alleviates Chronic Epilepsy and Abnormal Plasticity, and Maintains Better Memory and Mood Function[J]. Aging and disease, 2020, 11(6): 1374-1394.
[8] Wei-Xing Ma,Jing Tang,Zhi-Wen Lei,Chun-Yan Li,Li-Qing Zhao,Chao Lin,Tao Sun,Zheng-Yi Li,Ying-Hui Jiang,Jun-Tao Jia,Cheng-Zhu Liang,Jun-Hong Liu,Liang-Jun Yan. Potential Biochemical Mechanisms of Brain Injury in Diabetes Mellitus[J]. Aging and disease, 2020, 11(4): 978-987.
[9] Seong Gak Jeon, Anji Yoo, Dong Wook Chun, Sang Bum Hong, Hyunju Chung, Jin-il Kim, Minho Moon. The Critical Role of Nurr1 as a Mediator and Therapeutic Target in Alzheimer’s Disease-related Pathogenesis[J]. Aging and disease, 2020, 11(3): 705-724.
[10] Hefeng Zhou, Shengnan Li, Chuwen Li, Xuanjun Yang, Haitao Li, Hanbing Zhong, Jia-Hong Lu, Simon Ming-Yuen Lee. Oxyphylla A Promotes Degradation of α-Synuclein for Neuroprotection via Activation of Immunoproteasome[J]. Aging and disease, 2020, 11(3): 559-574.
[11] Weiwei Zhong, Yan Yuan, Xiaohuan Gu, Samuel In-young Kim, Ryan Chin, Modupe Loye, Thomas A Dix, Ling Wei, Shan Ping Yu. Neuropsychological Deficits Chronically Developed after Focal Ischemic Stroke and Beneficial Effects of Pharmacological Hypothermia in the Mouse[J]. Aging and disease, 2020, 11(1): 1-16.
[12] Ya-Fan Zhou, Jing Wang, Man-Fei Deng, Bin Chi, Na Wei, Jian-Guo Chen, Dan Liu, Xiaoping Yin, Youming Lu, Ling-Qiang Zhu. The Peptide-Directed Lysosomal Degradation of CDK5 Exerts Therapeutic Effects against Stroke[J]. Aging and disease, 2019, 10(5): 1140-1145.
[13] Chun-Sheng Yang, Ai Guo, Yulin Li, Kaibin Shi, Fu-Dong Shi, Minshu Li. Dl-3-n-butylphthalide Reduces Neurovascular Inflammation and Ischemic Brain Injury in Mice[J]. Aging and disease, 2019, 10(5): 964-976.
[14] Xu-Xu Deng, Shan-Shan Li, Feng-Yan Sun. Necrostatin-1 Prevents Necroptosis in Brains after Ischemic Stroke via Inhibition of RIPK1-Mediated RIPK3/MLKL Signaling[J]. Aging and disease, 2019, 10(4): 807-817.
[15] Xianmei Li, Siyang Lin, Xiaoli Chen, Wensi Huang, Qian Li, Hongxia Zhang, Xudong Chen, Shaohua Yang, Kunlin Jin, Bei Shao. The Prognostic Value of Serum Cytokines in Patients with Acute Ischemic Stroke[J]. Aging and disease, 2019, 10(3): 544-556.
Viewed
Full text


Abstract

Cited

  Shared   
Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail: editorial@aginganddisease.org
Powered by Beijing Magtech Co. Ltd