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Aging and disease    2016, Vol. 7 Issue (4) : 450-465     DOI: 10.14336/AD.2015.1123
Original Article |
Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage
Rolova Taisia1, Dhungana Hiramani1, Korhonen Paula1, Valonen Piia1, Kolosowska Natalia1, Konttinen Henna1, Kanninen Katja1, Tanila Heikki1,2, Malm Tarja1, Koistinaho Jari1,*
1Department of Neurobiology, A.I. Virtanen Institute, University of Eastern Finland
2Department of Neurology, Kuopio University Hospital, Kuopio, Finland
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Abstract  

Transient forebrain ischemia induces delayed death of the hippocampal pyramidal neurons, particularly in the CA2 and medial CA1 area. Early pharmacological inhibition of inflammatory response can ameliorate neuronal death, but it also inhibits processes leading to tissue regeneration. Therefore, research efforts are now directed to modulation of post-ischemic inflammation, with the aim to promote beneficial effects of inflammation and limit adverse effects. Transcription factor NF-κB plays a key role in the inflammation and cell survival/apoptosis pathways. In the brain, NF-κB is predominantly found in the form of a heterodimer of p65 (RelA) and p50 subunit, where p65 has a transactivation domain while p50 is chiefly involved in DNA binding. In this study, we subjected middle-aged Nfkb1 knockout mice (lacking p50 subunit) and wild-type controls of both sexs to 17 min of transient forebrain ischemia and assessed mouse performance in a panel of behavioral tests after two weeks of post-operative recovery. We found that ischemia failed to induce clear memory and motor deficits, but affected spontaneous locomotion in genotype- and sex-specific way. We also show that both the lack of the NF-κB p50 subunit and female sex independently protected CA2 hippocampal neurons from ischemia-induced cell death. Additionally, the NF-κB p50 subunit deficiency significantly reduced ischemia-induced microgliosis, astrogliosis, and neurogenesis. Lower levels of hippocampal microgliosis significantly correlated with faster spatial learning. We conclude that NF-κB regulates the outcome of transient forebrain ischemia in middle-aged subjects in a sex-specific way, having an impact not only on neuronal death but also specific inflammatory responses and neurogenesis.

Keywords cerebrovascular disease      neuroinflammation      neurogenesis      memory      transgenic mice     
Corresponding Authors: Koistinaho Jari   
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These authors had equal contribution and are designated as co-first authors.

Issue Date: 01 August 2016
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Rolova Taisia
Dhungana Hiramani
Korhonen Paula
Valonen Piia
Kolosowska Natalia
Konttinen Henna
Kanninen Katja
Tanila Heikki
Malm Tarja
Koistinaho Jari
Cite this article:   
Rolova Taisia,Dhungana Hiramani,Korhonen Paula, et al. Deletion of Nuclear Factor kappa B p50 Subunit Decreases Inflammatory Response and Mildly Protects Neurons from Transient Forebrain Ischemia-induced Damage[J]. Aging and disease, 2016, 7(4): 450-465.
URL:  
http://www.aginganddisease.org/EN/10.14336/AD.2015.1123     OR     http://www.aginganddisease.org/EN/Y2016/V7/I4/450
Figure 1.  Experimental setup. Wk, week; MWM, Morris Water Maze (swim task).
Figure 2.  The effect of Nfkb1 gene deficiency on mouse spatial learning and memory as assessed by Morris swim task during the week 4 after the BCCAo. (A-B) The length of a path to the hidden platform was assessed over five test days in female (A) and male mice (B). (C) 15 min memory retention expressed as the mean distance to the center of the previous platform location. The data are shown as mean ± SEM. P values are derived from two-way repeated measures or simple two-way ANOVA; * p < 0.05 in comparison to the Nfkb1-wt animals.
Figure 3.  The effects of Nfkb1 gene deficiency and female sex on activity in the open field test assessed during the week 3 after the BCCAo. Total distance moved (A), time spent in the center of the open field (B), the number of fecal pellets produced (C) and the number of rearings (D) during 10 min of free exploration of the novel arena. P values are derived from three-way ANOVA followed by pairwise comparisons with Bonferroni’s adjustment; # p < 0.05, ### p < 0.001 in comparison to the corresponding sham-operated controls; ** p < 0.01, *** p < 0.001 in comparison to the Nfkb1-wt animals.
Figure 4.  Neuronal loss in the hippocampus was predominantly observed in the CA2 area (A, rectangle) and CA1 area (A, arrow) five weeks after the BCCAo. (A) A representative image of NeuN immunostaining in the hippocampal area of ischemic mouse, scale bar = 500 μm; (C-H), representative higher magnification images of NeuN staining in CA2 area in male (C-E) and female (F-H) ischemic Nfkb1-wt (C, F), ischemic Nfkb1-ko (D, G) and sham Nfkb1-wt (E, H) animals, scale bar = 100 μm. (B) NeuN immunoreactivity in the CA2 area as delineated with a rectangle in images (C-H) and expressed as the percentage of the average value in the wt sham group (females and males normalized separately). P values are derived from three-way ANOVA followed by pairwise comparisons with Bonferroni’s adjustment; * p < 0.05 in comparison to the ischemic Nfkb1-wt animals; # p < 0.05, ## p < 0.01 in comparison to the corresponding sham-treated controls.
Figure 5.  Astrocytosis was evaluated by immunostaining with anti-GFAP antibody five weeks after the BCCAo. Astrocytosis was evaluated by immunostaining with anti-GFAP antibody and was observed predominantly in the CA1, CA2 and dentate gyrus (DG) regions of ischemic hippocampus (A) as compared to sham-operated animals (B), scale bar = 500 μm. GFAP immunoreactivity was evaluated in the whole hippocampal area (C) delineated by solid boundary line in (A) and expressed as the percentage of the whole area of interest. P values are derived from three-way ANOVA followed by pairwise comparisons with Bonferroni’s adjustment; * p < 0.05 in comparison to the Nfkb1-wt animals; # p < 0.05, ## p < 0.01, ### p < 0.001 in comparison to the sham-treated controls. Panel (D-I) representative images of GFAP immunoreactivity in the CA2 area of ischemic Nfkb1-wt and ko animals and wt sham controls, scale bar = 100 μm.
Figure 6.  Microgliosis was evaluated by anti-CD45 immunostaining five weeks after the BCCAo. (A), total CD45 immunoreactivity was evaluated in the whole hippocampal area (as delineated in Figure 5 A) and expressed as the percentage of the area of interest. Panel (B-I), representative images of CD45 immunostaining in the whole hippocampal area (B, C) or only CA2 area in the Nfkb1-wt ischemic mice (B, D, G), Nfkb1-ko ischemic mice (E, H) and Nfkb1-wt sham-operated mice (C, F, I). Scale bar in (B-C) equals 500 μm; scale bar in (D-I) equals 100 μm; DG, dentate gyrus. (J-L), CD45 immunoreactivity in CD45high-expressing cells (J; red) co-localized with Iba1-immunoreactivity (K, L; green). (M), the average number of CD45high small round cells (shown in (K-L)) per section. (N-O), a representative picture of Iba1 staining in the CA2 area of the ischemic hippocampus, scale bar equals 100 μm (N) and quantification of Iba1 immunoreactivity in the whole hippocampal area in male mice (O). P values are derived from three-way ANOVA followed by pairwise comparisons with Bonferroni’s adjustment. *** p < 0.001 in comparison to the Nfkb1-wt animals; # p < 0.05, ## p < 0.01, ### p < 0.001 in comparison to the sham-treated controls.
Figure 7.  Neurogenesis in the dentate gyrus area was evaluated by anti-DCX (doublecortin) immunostaining five weeks after the BCCAo. (A-F) Representative images of DCX immunoreactivity in ischemic animals (A, B, D, E), and sham-treated controls (C, F). (D-F) Higher magnification images of the areas delineated with a rectangle in (A-C). Str. gr., stratum granulare (the granular layer); str. mol., stratum moleculare (the molecular layer); arrowheads show post-mitotic immature neurons. Scale bar in (A-C) equals 200 μm; scale bar in (D-F) equals 80 μm. (G) The average number of DCX-positive cell profiles per section. P values are derived from three-way ANOVA followed by pairwise comparisons with Bonferroni’s adjustment; * p < 0.05 in comparison to the Nfkb1-wt animals, ## p < 0.01 main sex effect. (H, I) Correlations between the average number of DCX+ cells and total CD45 immunoreactivity in the hippocampus (two hippocampi per animal analyzed separately) in female (H) and male animals (I). Spearman’s rho (nonparametric) correlation coefficient R was calculated separately for hippocampi with CD45 immunoreactivity < 9.5% (< 10% in the case of females) shown on the left side of the correlation plot and CD45 immunoreactivity > 9.5% shown on the right.
GenderGenotypeBody weight, gPcommAs per animal
MaleNfkb1-wt34.5 ± 0.61.3 ± 0.2
Nfkb1-ko35.4 ± 0.71.4 ± 0.1
FemaleNfkb1-wt26.1 ± 0.61.5 ± 0.1
Nfkb1-ko23.4 ± 0.3***1.3 ± 0.2
Supplementary table 1  Average body weight and the number of posterior communicating arteries (PcommAs) per animal in the wt and Nfkb1-ko male and female mice. Data are shown as mean ± SEM. P values are derived from Student’s t-test; *** p < 0.001 in comparison to the wt female animals.
GenderGenotypeTreatmentArea of the hippocampus
Medial CA1CA2
MaleNfkb1-wtIschemia88.1 ± 6.0 (p = 0.068)75.4 ± 5.3 (p = 0.003)
Sham100.0 ± 2.3100.0 ± 3.6
Nfkb1-koIschemia91.2 ± 2.7 (p = 0.056)82.5 ± 4.1 (p = 0.014)
Sham103.4 ± 2.9102.1 ± 2.4
FemaleNfkb1-wtIschemia101.2 ± 2.0 (p = 0.692)81.8 ± 4.4 (p = 0.005)
Sham100.0 ± 2.0100.0 ± 3.0
Nfkb1-koIschemia101.2 ± 2.2 (p = 0.391)91.5 ± 3.5 (p = 0.061)
Sham104.2 ± 2.7104.5 ± 2.6
Supplementary table 2  NeuN immunoreactivity in medial CA1 and CA2 areas (delineated in Fig. 3) expressed as the percentage of average immunoreactivity in wt sham animals (females and males normalised separately). Data are shown as mean ± SEM. P values are derived from two-way ANOVA followed by pairwise comparisons with Bonferroni’s adjustment and are shown in brackets.
[1] Petito CK, Feldmann E, Pulsinelli WA, Plum F (1987). Delayed hippocampal damage in humans following cardiorespiratory arrest. Neurology, 37: 1281-1286
[2] Pulsinelli WA, Brierley JB (1979). A new model of bilateral hemispheric ischemia in the unanesthetized rat. Stroke, 10: 267-272
[3] Kelly S, McCulloch J, Horsburgh K (2001). Minimal ischaemic neuronal damage and HSP70 expression in MF1 strain mice following bilateral common carotid artery occlusion. Brain Res, 914: 185-195
[4] Fujii M, Hara H, Meng W, Vonsattel JP, Huang Z, Moskowitz MA (1997). Strain-related differences in susceptibility to transient forebrain ischemia in SV-129 and C57black/6 mice. Stroke, 28: 1805-1810. discussion 1811
[5] Yang G, Kitagawa K, Matsushita K, Mabuchi T, Yagita Y, Yanagihara T, et al. (1997). C57BL/6 strain is most susceptible to cerebral ischemia following bilateral common carotid occlusion among seven mouse strains: selective neuronal death in the murine transient forebrain ischemia. Brain Res, 752: 209-218
[6] Hamby AM, Suh SW, Kauppinen TM, Swanson RA (2007). Use of a poly(ADP-ribose) polymerase inhibitor to suppress inflammation and neuronal death after cerebral ischemia-reperfusion. Stroke, 38: 632-636
[7] Candelario-Jalil E, Alvarez D, Gonzalez-Falcon A, Garcia-Cabrera M, Martinez-Sanchez G, Merino N, et al. (2002). Neuroprotective efficacy of nimesulide against hippocampal neuronal damage following transient forebrain ischemia. Eur J Pharmacol, 453: 189-195
[8] Kauppinen TM, Suh SW, Berman AE, Hamby AM, Swanson RA (2009). Inhibition of poly(ADP-ribose) polymerase suppresses inflammation and promotes recovery after ischemic injury. J Cereb Blood Flow Metab, 29: 820-829
[9] Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koistinaho J (1998). Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci U S A, 95: 15769-15774
[10] Neher JJ, Emmrich JV, Fricker M, Mander PK, Thery C, Brown GC (2013). Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc Natl Acad Sci U S A, 110: E4098-4107
[11] Ekdahl CT, Kokaia Z, Lindvall O (2009). Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience, 158: 1021-1029
[12] Denes A, Vidyasagar R, Feng J, Narvainen J, McColl BW, Kauppinen RA, et al. (2007). Proliferating resident microglia after focal cerebral ischaemia in mice. J Cereb Blood Flow Metab, 27: 1941-1953
[13] Neumann H, Kotter MR, Franklin RJ (2009). Debris clearance by microglia: an essential link between degeneration and regeneration. Brain, 132: 288-295
[14] Neumann J, Sauerzweig S, Ronicke R, Gunzer F, Dinkel K, Ullrich O, et al. (2008). Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege. J Neurosci, 28: 5965-5975
[15] Lalancette-Hebert M, Gowing G, Simard A, Weng YC, Kriz J (2007). Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci, 27: 2596-2605
[16] Kim BJ, Kim MJ, Park JM, Lee SH, Kim YJ, Ryu S, et al. (2009). Reduced neurogenesis after suppressed inflammation by minocycline in transient cerebral ischemia in rat. J Neurol Sci, 279: 70-75
[17] Sasaki T, Kitagawa K, Sugiura S, Omura-Matsuoka E, Tanaka S, Yagita Y, et al. (2003). Implication of cyclooxygenase-2 on enhanced proliferation of neural progenitor cells in the adult mouse hippocampus after ischemia. J Neurosci Res, 72: 461-471
[18] Baldwin ASJr. (1996). The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol, 14: 649-683
[19] Kaltschmidt C, Kaltschmidt B, Neumann H, Wekerle H, Baeuerle PA (1994). Constitutive NF-kappa B activity in neurons. Mol Cell Biol, 14: 3981-3992
[20] Kunsch C, Ruben SM, Rosen CA (1992). Selection of optimal kappa B/Rel DNA-binding motifs: interaction of both subunits of NF-kappa B with DNA is required for transcriptional activation. Mol Cell Biol, 12: 4412-4421
[21] Clemens JA, Stephenson DT, Dixon EP, Smalstig EB, Mincy RE, Rash KS, et al. (1997). Global cerebral ischemia activates nuclear factor-kappa B prior to evidence of DNA fragmentation. Brain Res Mol Brain Res, 48: 187-196
[22] Clemens JA, Stephenson DT, Smalstig EB, Dixon EP, Little SP (1997). Global ischemia activates nuclear factor-kappa B in forebrain neurons of rats. Stroke, 28: 1073-1080; discussion 1080-1071
[23] Nurmi A, Vartiainen N, Pihlaja R, Goldsteins G, Yrjanheikki J, Koistinaho J (2004). Pyrrolidine dithiocarbamate inhibits translocation of nuclear factor kappa-B in neurons and protects against brain ischaemia with a wide therapeutic time window. J Neurochem, 91: 755-765
[24] Nurmi A, Lindsberg PJ, Koistinaho M, Zhang W, Juettler E, Karjalainen-Lindsberg ML, et al. (2004). Nuclear factor-kappaB contributes to infarction after permanent focal ischemia. Stroke, 35: 987-991
[25] Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, Schwaninger M (1999). NF-kappaB is activated and promotes cell death in focal cerebral ischemia. Nat Med, 5: 554-559
[26] Sha WC, Liou HC, Tuomanen EI, Baltimore D (1995). Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses. Cell, 80: 321-330
[27] Heikkinen R, Malm T, Heikkila J, Muona A, Tanila H, Koistinaho M, et al. (2014). Susceptibility to focal and global brain ischemia of Alzheimer mice displaying abeta deposits: effect of immunoglobulin. Aging Dis, 5: 76-87
[28] Kemppainen S, Hamalainen E, Miettinen PO, Koistinaho J, Tanila H (2014). Behavioral and neuropathological consequences of transient global ischemia in APP/PS1 Alzheimer model mice. Behav Brain Res, 275C: 15-26
[29] Rolova T, Puli L, Magga J, Dhungana H, Kanninen K, Wojciehowski S, et al. (2014). Complex regulation of acute and chronic neuroinflammatory responses in mouse models deficient for nuclear factor kappa B p50 subunit. Neurobiol Dis, 64: 16-29
[30] Neubrand VE, Pedreno M, Caro M, Forte-Lago I, Delgado M, Gonzalez-Rey E (2014). Mesenchymal stem cells induce the ramification of microglia via the small RhoGTPases Cdc42 and Rac1. Glia, 62: 1932-1942
[31] Dibaj P, Nadrigny F, Steffens H, Scheller A, Hirrlinger J, Schomburg ED, et al. (2010). NO mediates microglial response to acute spinal cord injury under ATP control in vivo. Glia, 58: 1133-1144
[32] Kim DH, Kim JM, Park SJ, Lee S, Yoon BH, Ryu JH (2010). Early-activated microglia play a role in transient forebrain ischemia-induced neural precursor proliferation in the dentate gyrus of mice. Neurosci Lett, 475: 74-79
[33] Kim DH, Lee HE, Kwon KJ, Park SJ, Heo H, Lee Y, et al. (2015). Early immature neuronal death initiates cerebral ischemia-induced neurogenesis in the dentate gyrus. Neuroscience, 284: 42-54.
[34] Liu J, Solway K, Messing RO, Sharp FR (1998). Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils. J Neurosci, 18: 7768-7778
[35] Song H, Stevens CF, Gage FH (2002). Astroglia induce neurogenesis from adult neural stem cells. Nature, 417: 39-44
[36] Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG (2003). Transient expression of doublecortin during adult neurogenesis. J Comp Neurol, 467: 1-10
[37] Herrmann O, Baumann B, de Lorenzi R, Muhammad S, Zhang W, Kleesiek J, et al. (2005). IKK mediates ischemia-induced neuronal death. Nat Med, 11: 1322-1329
[38] Zhang W, Potrovita I, Tarabin V, Herrmann O, Beer V, Weih F, et al. (2005). Neuronal activation of NF-kappaB contributes to cell death in cerebral ischemia. J Cereb Blood Flow Metab, 25: 30-40
[39] Kettenmann H, Hanisch UK, Noda M, Verkhratsky A (2011). Physiology of microglia. Physiol Rev, 91: 461-553
[40] Hu X, Leak RK, Shi Y, Suenaga J, Gao Y, Zheng P, et al. (2015). Microglial and macrophage polarization-new prospects for brain repair. Nat Rev Neurol, 11: 56-64
[41] Liao B, Zhao W, Beers DR, Henkel JS, Appel SH (2012). Transformation from a neuroprotective to a neurotoxic microglial phenotype in a mouse model of ALS. Exp Neurol, 237: 147-152
[42] Porta C, Rimoldi M, Raes G, Brys L, Ghezzi P, Di Liberto D, et al. (2009). Tolerance and M2 (alternative) macrophage polarization are related processes orchestrated by p50 nuclear factor kappaB. Proc Natl Acad Sci U S A, 106: 14978-14983
[43] Taetzsch T, Levesque S, McGraw C, Brookins S, Luqa R, Bonini MG, et al. (2015). Redox regulation of NF-kappaB p50 and M1 polarization in microglia. Glia, 63: 423-440
[44] Puli L, Pomeshchik Y, Olas K, Malm T, Koistinaho J, Tanila H (2012). Effects of human intravenous immunoglobulin on amyloid pathology and neuroinflammation in a mouse model of Alzheimer's disease. J Neuroinflammation, 9: 105
[45] Bernal GM, Wahlstrom JS, Crawley CD, Cahill KE, Pytel P, Liang H, Kang S, Weichselbaum RR (2014). Loss of Nfkb1 leads to early onset aging. Aging, 6: 931-943
[46] Lu ZY, Yu SP, Wei JF, Wei L (2006). Age-related neural degeneration in nuclear-factor kappaB p50 knockout mice. Neuroscience, 139: 965-978
[47] Lang H, Schulte BA, Zhou D, Smythe N, Spicer SS, Schmiedt RA (2006). Nuclear factor kappaB deficiency is associated with auditory nerve degeneration and increased noise-induced hearing loss. J Neurosci, 26: 3541-3550
[48] Nakamura-Yanagidaira T, Takahashi Y, Sano K, Murata T, Hayashi T (2011). Development of spontaneous neuropathy in NF-kappaBp50-deficient mice by calcineurin-signal involving impaired NF-kappaB activation. Molecular vision, 17: 2157-2170
[49] Takahashi Y, Katai N, Murata T, Taniguchi SI, Hayashi T (2007). Development of spontaneous optic neuropathy in NF-kappaBetap50-deficient mice: requirement for NF-kappaBetap50 in ganglion cell survival. Neuropathol Appl Neurobiol, 33: 692-705
[50] Kolosova NG, Vitovtov AO, Muraleva NA, Akulov AE, Stefanova NA, Blagosklonny MV (2013). Rapamycin suppresses brain aging in senescence-accelerated OXYS rats. Aging, 5: 474-484
[51] Kassed CA, Herkenham M (2004). NF-kappaB p50-deficient mice show reduced anxiety-like behaviors in tests of exploratory drive and anxiety. Behav Brain Res, 154: 577-584
[52] Denis-Donini S, Dellarole A, Crociara P, Francese MT, Bortolotto V, Quadrato G, et al. (2008). Impaired adult neurogenesis associated with short-term memory defects in NF-kappaB p50-deficient mice. J Neurosci, 28: 3911-3919
[53] Lehmann ML, Brachman RA, Listwak SJ, Herkenham M (2010). NF-kappaB activity affects learning in aversive tasks: possible actions via modulation of the stress axis. Brain Behav Immun, 24: 1008-1017
[54] Crawley JN, Belknap JK, Collins A, Crabbe JC, Frankel W, Henderson N, et al. (1997). Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology, 132: 107-124
[55] Eisener-Dorman AF, Lawrence DA, Bolivar VJ (2010). Behavioral and genetic investigations of low exploratory behavior in Il18r1(-/-) mice: we can't always blame it on the targeted gene. Brain Behav Immun, 24: 1116-1125
[56] de Ledesma AM, Desai AN, Bolivar VJ, Symula DJ, Flaherty L (2006). Two new behavioral QTLs, Emo4 and Reb1, map to mouse Chromosome 1: Congenic strains and candidate gene identification studies. Mamm Genome, 17: 111-118
[57] Tanaka R, Yamashiro K, Mochizuki H, Cho N, Onodera M, Mizuno Y, et al. (2004). Neurogenesis after transient global ischemia in the adult hippocampus visualized by improved retroviral vector. Stroke, 35: 1454-1459
[58] Raber J, Fan Y, Matsumori Y, Liu Z, Weinstein PR, Fike JR, et al. (2004). Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Ann Neurol, 55: 381-389
[59] Ortega FJ, Jolkkonen J, Mahy N, Rodriguez MJ (2013). Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia. J Cereb Blood Flow Metab, 33: 356-364
[60] Rodriguez-Grande B, Varghese L, Molina-Holgado F, Rajkovic O, Garlanda C, Denes A, et al. (2015). Pentraxin 3 mediates neurogenesis and angiogenesis after cerebral ischaemia. J Neuroinflammation, 12: 15
[61] Kuhn HG, Dickinson-Anson H, Gage FH (1996). Neurogenesis in the dentate gyrus of the adult rat: age-related decrease of neuronal progenitor proliferation. J Neurosci, 16: 2027-2033
[62] Gil-Mohapel J, Brocardo PS, Choquette W, Gothard R, Simpson JM, Christie BR (2013). Hippocampal neurogenesis levels predict WATERMAZE search strategies in the aging brain. PLoS One, 8: e75125
[63] Bellinger FP, Madamba S, Siggins GR (1993). Interleukin 1 beta inhibits synaptic strength and long-term potentiation in the rat CA1 hippocampus. Brain Res, 628: 227-234
[64] Bellinger FP, Madamba SG, Campbell IL, Siggins GR (1995). Reduced long-term potentiation in the dentate gyrus of transgenic mice with cerebral overexpression of interleukin-6. Neurosci Lett, 198: 95-98
[65] Butler MP, O'Connor JJ, Moynagh PN (2004). Dissection of tumor-necrosis factor-alpha inhibition of long-term potentiation (LTP) reveals a p38 mitogen-activated protein kinase-dependent mechanism which maps to early-but not late-phase LTP. Neuroscience, 124: 319-326
[66] Rogers JT, Morganti JM, Bachstetter AD, Hudson CE, Peters MM, Grimmig BA, et al. (2011). CX3CR1 deficiency leads to impairment of hippocampal cognitive function and synaptic plasticity. J Neurosci, 31: 16241-16250
[67] Milot MR, Plamondon H (2009). Time-dependent effects of global cerebral ischemia on anxiety, locomotion, and habituation in rats. Behav Brain Res, 200: 173-80
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