Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Ischemic stroke is a major disability and cause of death worldwide due to its narrow therapeutic time window. Neuroprotective agent is a promising strategy to salvage acutely ischemic brain tissue and extend the therapeutic time window for stroke treatment. In this study, we aimed to evaluate the neuroprotective effects of isoquercetin in (1) primary culture of rat hippocampal neurons exposure on oxygen and glucose deprivation and reperfusion (OGD/R) injury and (2) rats subjected to transient middle cerebral artery occlusion and reperfusion (MCAO/R) injury. The results showed that isoquercetin post-treatment reduced the infarct size, number of apoptotic cells, oxidative stress, and inflammatory response after ischemia and reperfusion injury. The underlying mechanism study indicated that the neuroprotective effects of isoquercetin were elicited via suppressing the activation of toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and caspase-1; the phosphorylation of ERK1/2, JNK1/2, and p38 mitogen-activated protein kinase (MAPK); and the secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6. In addition, isoquercetin also effectively alleviated hippocampus neuron apoptosis by regulation of cyclic AMP responsive element-binding protein (CREB), Bax, Bcl-2, and caspase-3. Our report provided new considerations into the therapeutic action and the underlying mechanisms of isoquercetin to improve brain injury in individuals who have suffered from ischemic stroke. As a potent anti-inflammatory and anti-oxidative compound with neuroprotective capacities, the beneficial effects of isoquercetin when used to treat ischemic stroke and related diseases in humans warrant further studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Abbreviations

CREB:

Cyclic AMP responsive element-binding protein

DMEM:

Dulbecco’s modified Eagle’s medium

ELISA:

Enzyme-linked immunosorbent assay

FBS:

Fetal bovine serum

H&E:

Hematoxylin and eosin

IHC:

Immunohistochemistry

IL:

Interleukin

IкB:

Inhibitor of nuclear factor-kappa B protein

JNK:

c-Jun NH2-terminal kinase

LDH:

Lactate dehydrogenase

MAPK:

Mitogen-activated protein kinase

MCAO:

Middle cerebral artery occlusion

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

NF-кB:

Nuclear factor-kappa B

OGD:

Oxygen and glucose deprivation

PBS:

Phosphate-buffered saline

R:

Reperfusion

SD:

Sprague–Dawley

TLR4:

Toll-like receptor 4

TTC:

2,3,5-Triphenyltetrazolium chloride

TUNEL:

Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling

References

  1. Nunez-Figueredo Y, Ramirez-Sanchez J, Hansel G, Pires ENS, Merino N, Valdes O, Delgado-Hernandez R, Parra AL, Ochoa-Rodriguez E, Verdecia-Reyes Y, Salbego C, Costa SL, Souza DO, Pardo-Andreu GL (2014) A novel multi-target ligand (JM-20) protects mitochondrial integrity, inhibits brain excitatory amino acid release and reduces cerebral ischemia injury in vitro and in vivo. Neuropharmacology 85:517–527

    Article  CAS  PubMed  Google Scholar 

  2. Cheng YL, Park JS, Manzanero S, Choi Y, Baik SH, Okun E, Gelderblom M, Fann DYW, Magnus T, Launikonis BS, Mattson MP, Sobey CG, Jo DG, Arumugam TV (2014) Evidence that collaboration between HIF-1 alpha and Notch-1 promotes neuronal cell death in ischemic stroke. Neurobiol Dis 62:286–295

    Article  CAS  PubMed  Google Scholar 

  3. Wang Y, Jia J, Ao G, Hu L, Liu H, Xiao Y, Du H, Alkayed NJ, Liu CF, Cheng J (2014) Hydrogen sulfide protects blood–brain barrier integrity following cerebral ischemia. J Neurochem 129:827–838

    Article  CAS  PubMed  Google Scholar 

  4. Xiong XX, White RE, Xu LJ, Yang LY, Sun XY, Zou BD, Pascual C, Sakurai T, Giffard RG, Xie XM (2013) Mitigation of murine focal cerebral ischemia by the hypocretin/orexin system is associated with reduced inflammation. Stroke 44:764–770

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rautiainen S, Larsson S, Virtamo J, Wolk A (2012) Total antioxidant capacity of diet and risk of stroke a population-based prospective cohort of women. Stroke 43:335–340

    Article  CAS  PubMed  Google Scholar 

  6. Posada-Duque RA, Barreto GE, Cardona-Gomez GP (2014) Protection after stroke: cellular effectors of neurovascular unit integrity. Front Cell Neurosci 8:231–250

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lapchak PA (2011) Neuroprotective and neurotrophic curcuminoids to treat stroke: a translational perspective. Expert Opin Investig Drugs 20:13–22

    Article  CAS  PubMed  Google Scholar 

  8. Yanagihara N, Zhang H, Toyohira Y, Takahashi K, Ueno S, Tsutsui M, Takahashi K (2014) New insights into the pharmacological potential of plant flavonoids in the catecholamine system. J Pharmacol Sci 124:123–128

    Article  CAS  PubMed  Google Scholar 

  9. McCullough ML, Peterson JJ, Patel R, Jacques PF, Shah R, Dwyer JT (2012) Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr 95:454–464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Guo Y, Bruno RS (2015) Endogenous and exogenous mediators of quercetin bioavailability. J Nutr Biochem 26:201–210

    Article  PubMed  Google Scholar 

  11. Manach C, Morand C, Demigne C, Texier O, Regerat F, Remesy C (1997) Bioavailability of rutin and quercetin in rats. FEBS Lett 409:12–16

    Article  CAS  PubMed  Google Scholar 

  12. Morand C, Manach C, Crespy V, Remesy C (2000) Quercetin 3-O-beta-glucoside is better absorbed than other quercetin forms and is not present in rat plasma. Free Radic Res 33:667–676

    Article  CAS  PubMed  Google Scholar 

  13. Nieman DC, Henson DA, Maxwell KR, Williams AS, McAnulty SR, Jin FX, Shanely RA, Lines TC (2009) Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med Sci Sport Exerc 41:1467–1475

    Article  CAS  Google Scholar 

  14. Nieman DC (2010) Quercetin’s bioactive effects in human athletes. Curr Top Nutraceut Res 8:33–43

    CAS  Google Scholar 

  15. Wang CP, Li JL, Zhang LZ, Zhang XC, Yu S, Liang XM, Ding F, Wang ZW (2013) Isoquercetin protects cortical neurons from oxygen-glucose deprivation-reperfusion induced injury via suppression of TLR4-NF-kappaB signal pathway. Neurochem Int 63:741–749

    Article  CAS  PubMed  Google Scholar 

  16. Brewer GJ, Torricelli JR, Evege EK, Price PJ (1993) Optimized survival of hippocampal neurons in B27-supplemented neurobasal, a new serum-free medium combination. J Neurosci Res 35:567–576

    Article  CAS  PubMed  Google Scholar 

  17. Yan W, Fang Z, Yang Q, Dong H, Lu Y, Lei C, Xiong L (2013) Sirt1 mediates hyperbaric oxygen preconditioning-induced ischemic tolerance in rat brain. J Cereb Blood Flow Metab 33:396–406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ortega FJ, Jolkkonen J, Mahy N, Rodriguez MJ (2013) Glibenclamide enhances neurogenesis and improves long-term functional recovery after transient focal cerebral ischemia. J Cerebr Blood F Met 33:356–364

    Article  CAS  Google Scholar 

  19. Zhou L, Li F, Xu HB, Luo CX, Wu HY, Zhu MM, Lu W, Ji X, Zhou QG, Zhu DY (2010) Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. Nat Med 16:1439–1443

    Article  CAS  PubMed  Google Scholar 

  20. Lin TN, He YY, Wu G, Khan M, Hsu CY (1993) Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats. Stroke 24:117–121

    Article  CAS  PubMed  Google Scholar 

  21. Bian QM, Shi T, Chuang DM, Qian YI (2007) Lithium reduces ischemia-induced hippocampal CA1 damage and behavioral deficits in gerbils. Brain Res 1184:270–276

    Article  CAS  PubMed  Google Scholar 

  22. Li SY, Yang D, Fu ZJ, Woo T, Wong D, Lo AC (2012) Lutein enhances survival and reduces neuronal damage in a mouse model of ischemic stroke. Neurobiol Dis 45:624–632

    Article  CAS  PubMed  Google Scholar 

  23. Li CJ, Lu Y, Zhou M, Zong XG, Li C, Xu XL, Guo LJ, Lu Q (2014) Activation of GABAB receptors ameliorates cognitive impairment via restoring the balance of HCN1/HCN2 surface expression in the hippocampal CA1 area in rats with chronic cerebral hypoperfusion. Mol Neurobiol 50:704–720

    Article  PubMed  Google Scholar 

  24. Bederson JB, Pitts LH, Tsuji M, Nishimura MC, Davis RL, Bartkowski H (1986) Rat middle cerebral artery occlusion: evaluation of the model and development of a neurologic examination. Stroke 17:472–476

    Article  CAS  PubMed  Google Scholar 

  25. Chan PH (2001) Reactive oxygen radicals in signaling and damage in the ischemic brain. J Cereb Blood Flow Metab 21:2–14

    Article  CAS  PubMed  Google Scholar 

  26. Chen H, Yoshioka H, Kim GS, Jung JE, Okami N, Sakata H, Maier CM, Narasimhan P, Goeders CE, Chan PH (2011) Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid Redox Signal 14:1505–1517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Tang SC, Arumugam TV, Xu XR, Cheng AW, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP (2007) Pivotal role for neuronal toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci U S A 104:13798–13803

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Suzuki Y, Hattori K, Hamanaka J, Murase T, Egashira Y, Mishiro K, Ishiguro M, Tsuruma K, Hirose Y, Tanaka H, Yoshimura S, Shimazawa M, Inagaki N, Nagasawa H, Iwama T, Hara H (2012) Pharmacological inhibition of TLR4-NOX4 signal protects against neuronal death in transient focal ischemia. Sci Rep 2:896–905

    PubMed  PubMed Central  Google Scholar 

  29. Kyriakis JM, Avruch J (2012) Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev 92:689–737

    Article  CAS  PubMed  Google Scholar 

  30. Cargnello M, Roux PP (2011) Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiol Mol Biol Rev 75:50–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Scholten N, Pfaff H, Lehmann HC, Fink GR, Karbach U (2015) Who does it first? The uptake of medical innovations in the performance of thrombolysis on ischemic stroke patients in Germany: a study based on hospital quality data. Implement Sci 10:10–19

    Article  PubMed  PubMed Central  Google Scholar 

  32. Merino-Zamorano C, Hernandez-Guillamon M, Jullienne A, Behot AL, Bardou I, Pares M, Fernandez-Cadenas I, Giralt D, Carrera C, Ribo M, Vivien D, Ali C, Rosell A, Montaner J (2015) NURR1 involvement in recombinant tissue-type plasminogen activator treatment complications after ischemic stroke. Stroke 46:477–484

    Article  CAS  PubMed  Google Scholar 

  33. Harwood M, Danielewska-Nikiel B, Borzelleca JF, Flamm GW, Williams GM, Lines TC (2007) A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 45:2179–2205

    Article  CAS  PubMed  Google Scholar 

  34. Hossmann KA (2008) Cerebral ischemia: models, methods and outcomes. Neuropharmacology 55:257–270

    Article  CAS  PubMed  Google Scholar 

  35. Gubern C, Hurtado O, Rodriguez R, Morales JR, Romera VG, Moro MA, Lizasoain I, Serena J, Mallolas J (2009) Validation of housekeeping genes for quantitative real-time PCR in in-vivo and in-vitro models of cerebral ischaemia. BMC Mol Biol 10:57–67

    Article  PubMed  PubMed Central  Google Scholar 

  36. Aridas JDS, Yawno T, Sutherland AE, Nitsos I, Ditchfield M, Wong FY, Fahey MC, Malhotra A, Wallace EM, Jenkin G, Miller SL (2014) Detecting brain injury in neonatal hypoxic ischemic encephalopathy: closing the gap between experimental and clinical research. Exp Neurol 261:281–290

    Article  PubMed  Google Scholar 

  37. Azzopardi D, Edwards AD (2010) Magnetic resonance biomarkers of neuroprotective effects in infants with hypoxic ischemic encephalopathy. Semin Fetal Neonatal Med 15:261–269

    Article  PubMed  Google Scholar 

  38. Seo KH, Lee DY, Jeong RH, Lee DS, Kim YE, Hong EK, Kim YC, Baek NI (2015) Neuroprotective effect of prenylated arylbenzofuran and flavonoids from Morus alba fruits on glutamate-induced oxidative injury in HT22 hippocampal cells. J Med Food 18:403–408

    Article  CAS  PubMed  Google Scholar 

  39. McAnulty SR, Nieman DC, McAnulty LS, Lynch WS, Jin FX, Henson DA (2011) Effect of mixed flavonoids, n-3 fatty acids, and vitamin c on oxidative stress and antioxidant capacity before and after intense cycling. Int J Sport Nutr Exerc Metab 21:328–337

    Article  CAS  PubMed  Google Scholar 

  40. Maddahi A, Povlsen GK, Edvinsson L (2012) Regulation of enhanced cerebrovascular expression of proinflammatory mediators in experimental subarachnoid hemorrhage via the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase pathway. J Neuroinflammation 9:274–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Liu F, Zhou R, Yan H, Yin H, Wu X, Tan Y, Li L (2014) Metabotropic glutamate receptor 5 modulates calcium oscillation and innate immune response induced by lipopolysaccharide in microglial cell. Neuroscience 281:24–34

    Article  CAS  PubMed  Google Scholar 

  42. Jiang MJ, Li J, Peng QX, Liu Y, Liu W, Luo CH, Peng J, Li JK, Yung KKL, Mo ZX (2014) Neuroprotective effects of bilobalide on cerebral ischemia and reperfusion injury are associated with inhibition of pro-inflammatory mediator production and down-regulation of JNK1/2 and p38 MAPK activation. J Neuroinflammation 11:167–184

    Article  PubMed  PubMed Central  Google Scholar 

  43. Maddahi A, Edvinsson L (2010) Cerebral ischemia induces microvascular pro-inflammatory cytokine expression via the MEK/ERK pathway. J Neuroinflammation 7:14–27

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ferrer I, Friguls B, Dalfo E, Planas AM (2003) Early modifications in the expression of mitogen-activated protein kinase (MAPK/ERK), stress-activated kinases SAPK/JNK and p38, and their phosphorylated substrates following focal cerebral ischemia. Acta Neuropathol 105:425–437

    CAS  PubMed  Google Scholar 

  45. Ravingerova T, Barancik M, Strniskova M (2003) Mitogen-activated protein kinases: a new therapeutic target in cardiac pathology. Mol Cell Biochem 247:127–138

    Article  CAS  PubMed  Google Scholar 

  46. Sawe N, Steinberg G, Zhao H (2008) Dual roles of the MAPK/ERK1/2 cell signaling pathway after stroke. J Neurosci Res 86:1659–1669

    Article  CAS  PubMed  Google Scholar 

  47. Dornbos D, Ding YC (2012) Mechanisms of neuronal damage and neuroprotection underlying ischemia/reperfusion injury after physical exercise. Curr Drug Targets 13:247–262

    Article  CAS  PubMed  Google Scholar 

  48. Tian HP, Huang BS, Zhao J, Hu XH, Guo J, Li LX (2009) Non-receptor tyrosine kinase Src is required for ischemia-stimulated neuronal cell proliferation via Raf/ERK/CREB activation in the dentate gyrus. BMC Neurosci 10:139–151

    Article  PubMed  PubMed Central  Google Scholar 

  49. Borsello T, Clarke PGH, Hirt L, Vercelli A, Repici M, Schorderet DF, Bogousslavsky J, Bonny C (2003) A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat Med 9:1180–1186

    Article  CAS  PubMed  Google Scholar 

  50. Pirianov G, Brywe KG, Mallard C, Edwards AD, Flavell RA, Hagberg H, Mehmet H (2007) Deletion of the c-Jun N-terminal kinase 3 gene protects neonatal mice against cerebral hypoxic-ischaemic injury. J Cerebr Blood F Met 27:1022–1032

    Article  CAS  Google Scholar 

  51. Lee MY, Jung SC, Lee JH, Han HJ (2008) Estradiol-17 beta protects against hypoxia-induced hepatocyte injury through ER-mediated upregulation of Bcl-2 as well as ER-independent antioxidant effects. Cell Res 18:491–499

    Article  CAS  PubMed  Google Scholar 

  52. Pan J, Zhang QG, Zhang GY (2005) The neuroprotective effects of K252a through inhibiting MLK3/MKK7/JNK3 signaling pathway on ischemic brain injury in rat hippocampal CA1 region. Neuroscience 131:147–159

    Article  CAS  PubMed  Google Scholar 

  53. Vila N, Castillo J, Davalos A, Chamorro A (2000) Proinflammatory cytokines and early neurological worsening in ischemic stroke. Stroke 31:2325–2329

    Article  CAS  PubMed  Google Scholar 

  54. Wang CX, Shuaib A (2002) Involvement of inflammatory cytokines in central nervous system injury. Prog Neurobiol 67:161–172

    Article  CAS  PubMed  Google Scholar 

  55. Barone FC, Irving EA, Ray AM, Lee JC, Kassis S, Kumar S, Badger AM, Legos JJ, Erhardt JA, Ohlstein EH, Hunter AJ, Harrison DC, Philpott K, Smith BR, Adams JL, Parsons AA (2001) Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Med Res Rev 21:129–145

    Article  CAS  PubMed  Google Scholar 

  56. Strassburger M, Braun H, Reymann KG (2008) Anti-inflammatory treatment with the p38 mitogen-activated protein kinase inhibitor SB239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen-glucose-deprived hippocampal slice cultures. Eur J Pharmacol 592:55–61

    Article  CAS  PubMed  Google Scholar 

  57. Benakis C, Bonny C, Hirt L (2010) JNK inhibition and inflammation after cerebral ischemia. Brain Behav Immun 24:800–811

    Article  CAS  PubMed  Google Scholar 

  58. Yasuda N, Ishii T, Oyama D, Fukuta T, Agato Y, Sato A, Shimizu K, Asai T, Asakawa T, Kan T, Yamada S, Ohizumi Y, Oku N (2014) Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats. Brain Res 1559:46–54

    Article  CAS  PubMed  Google Scholar 

  59. Lasarte JJ, Casares N, Gorraiz M, Hervas-Stubbs S, Arribillaga L, Mansilla C, Durantez M, Llopiz D, Sarobe P, Borras-Cuesta F, Prieto J, Leclerc C (2007) The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J Immunol 178:748–756

    Article  CAS  PubMed  Google Scholar 

  60. Khan MM, Gandhi C, Chauhan N, Stevens JW, Motto DG, Lentz SR, Chauhan AK (2012) Alternatively-spliced extra domain A of fibronectin promotes acute inflammation and brain injury after cerebral ischemia in mice. Stroke 43:1376–1382

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lakhan SE, Kirchgessner A, Hofer M (2009) Inflammatory mechanisms in ischemic stroke: therapeutic approaches. J Transl Med 7:97–108

    Article  PubMed  PubMed Central  Google Scholar 

  62. 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

    Article  CAS  PubMed  Google Scholar 

  63. Kuang X, Wang LF, Yu L, Li YJ, Wang YN, He Q, Chen C, Du JR (2014) Ligustilide ameliorates neuroinflammation and brain injury in focal cerebral ischemia/reperfusion rats: involvement of inhibition of TLR4/peroxiredoxin 6 signaling. Free Radic Biol Med 71:165–175

    Article  CAS  PubMed  Google Scholar 

  64. Iadecola C, Anrather J (2011) The immunology of stroke: from mechanisms to translation. Nat Med 17:796–808

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Shah IM, Macrae IM, Di Napoli M (2009) Neuroinflammation and neuroprotective strategies in acute ischaemic stroke—from bench to bedside. Curr Mol Med 9:336–354

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), Funding for Scientific Research of Nantong University (Grant Nos. 02021567 and 02021557), and National Natural Science Foundation of China (Grant Nos. 81501142, 81371389 and 81200932). The English writing of this manuscript was checked by Miss Stephanie Lieng (USA).

Author information

Author notes

    Authors and Affiliations

    1. Jiangsu Key Laboratory of Neuroregeneration, Nantong University, No. 19, Qixiu Road, Nantong, Jiangsu, 226001, People’s Republic of China

      Cai-Ping Wang, Yun-Wei Shi, Miao Tang, Xiao-Chuan Zhang, Yun Gu, Xin-Miao Liang, Zhi-Wei Wang & Fei Ding

    2. Co-Innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu, 226001, People’s Republic of China

      Cai-Ping Wang, Yun-Wei Shi, Miao Tang, Xiao-Chuan Zhang, Yun Gu, Xin-Miao Liang, Zhi-Wei Wang & Fei Ding

    3. Dalian Institute of Chemical Physics, The Chinese Academy of Sciences, Dalian, Liaoning, 116023, People’s Republic of China

      Xin-Miao Liang

    4. Department of Pharmacology, University of California, Irvine, CA, 92697, USA

      Zhi-Wei Wang

    Authors
    1. Cai-Ping Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yun-Wei Shi
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Miao Tang
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Xiao-Chuan Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Yun Gu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Xin-Miao Liang
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Zhi-Wei Wang
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Fei Ding
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Xin-Miao Liang, Zhi-Wei Wang or Fei Ding.

    Ethics declarations

    All the experimental and animal handling procedures were carried out in accordance with animal care guidelines and were approved ethically by the Administration Committee for Laboratory Animals, Jiangsu Province, China.

    Additional information

    Cai-Ping Wang and Yun-Wei Shi contributed equally to this work.

    Electronic Supplementary Material

    Below is the link to the electronic supplementary material.

    Supplementary Movies 1

    (AVI 438,092 kb)

    Supplementary Movies 2

    (AVI 441,491 kb)

    Supplementary Movies 3

    (AVI 442,268 kb)

    Supplementary Movies 4

    (AVI 443,227 kb)

    Supplementary Movies 5

    (AVI 443,139 kb)

    ESM 6

    (DOCX 12 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Wang, CP., Shi, YW., Tang, M. et al. 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 (2017). https://doi.org/10.1007/s12035-016-9806-5

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s12035-016-9806-5

    Keywords

    Search

    Navigation