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Effect of Physical and Social Components of Enriched Environment on Astrocytes Proliferation in Rats After Cerebral Ischemia/Reperfusion Injury

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Abstract

Treatment of enriched environment (EE) exerts neuroprotective effect in cerebral ischemia/reperfusion (I/R) injury. However, how the component of EE contributes to the functional recovery after brain ischemia remains unclear. Here we examined the effect of physical and social components of EE on poststroke astrocytes proliferation using an animal model of middle cerebral artery occlusion (MCAO) followed by reperfusion. Rats were divided into five groups: physical enrichment group (PE), social enrichment group (SE), physical and social enrichment group (PSE), ischemia + standard group (IS) and sham-operated + standard group (SS). In a set of behavioral tests, we demonstrated that animals in the enriched groups exhibited improved functional outcomes compared with those in standard group. Reduced infarct volume was only observed in PSE and PE groups. Double immunofluorescent labeling and western blot analysis revealed that rats in PSE and PE groups showed significantly more proliferated astrocytes and higher expression levels of brain-derived neurotrophic factor (BDNF) in the periinfarct cortex, compared with those in SE group. Astrocytes proliferation and BDNF expression were significantly correlated with functional outcomes. Collectively, this study suggests that physical activity is a more important component of EE regarding the effect on astrocytes proliferation and BDNF expression, which may contribute to the improved neurological function of stroke animals.

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References

  1. van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198

    Article  PubMed  Google Scholar 

  2. Mizutani K, Sonoda S, Karasawa N, Yamada K, Shimpo K, Chihara T, Takeuchi T, Hasegawa Y, Kubo KY (2013) Effects of exercise after focal cerebral cortex infarction on basal ganglion. Neurol Sci 34:861–867

    Article  PubMed  Google Scholar 

  3. Venna VR, Xu Y, Doran SJ, Patrizz A, McCullough LD (2014) Social interaction plays a critical role in neurogenesis and recovery after stroke. Transl Psychiatry 4:e351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Silver J, Miller JH (2004) Regeneration beyond the glial scar. Nat Rev Neurosci 5:146–156

    Article  CAS  PubMed  Google Scholar 

  5. Voskuhl RR, Peterson RS, Song B, Ao Y, Morales LB, Tiwari-Woodruff S, Sofroniew MV (2009) Reactive astrocytes form scar-like perivascular barriers to leukocytes during adaptive immune inflammation of the CNS. J Neurosci 29:11511–11522

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Trendelenburg G, Dirnagl U (2005) Neuroprotective role of astrocytes in cerebral ischemia: focus on ischemic preconditioning. Glia 50:307–320

    Article  PubMed  Google Scholar 

  7. Hayakawa K, Nakano T, Irie K, Higuchi S, Fujioka M, Orito K, Iwasaki K, Jin G, Lo EH, Mishima K, Fujiwara M (2010) Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice. J Cereb Blood Flow Metab 30:871–882

    Article  CAS  PubMed  Google Scholar 

  8. Béjot Y, Prigent-Tessier A, Cachia C, Giroud M, Mossiat C, Bertrand N, Garnier P, Marie C (2011) Time-dependent contribution of non neuronal cells to BDNF production after ischemic stroke in rats. Neurochem Int 58:102–111

    Article  PubMed  Google Scholar 

  9. Rossi C, Angelucci A, Costantin L, Braschi C, Mazzantini M, Babbini F, Fabbri ME, Tessarollo L, Maffei L, Berardi N, Caleo M (2006) Brain-derived neurotrophic factor (bdnf) is required for the enhancement of hippocampal neurogenesis following environmental enrichment. Eur J Neurosci 24:1850–1856

    Article  PubMed  Google Scholar 

  10. Murphy TH, Corbett D (2009) Plasticity during stroke recovery: from synapse to behaviour. Nat Rev Neurosci 10:861–872

    Article  CAS  PubMed  Google Scholar 

  11. Hermann DM, Chopp M (2012) Promoting brain remodelling and plasticity for stroke recovery: therapeutic promise and potential pitfalls of clinical translation. Lancet Neurol 11:369–380

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sun H, Zhang J, Zhang L, Liu H, Zhu H, Yang Y (2010) Environmental enrichment influences BDNF and NR1 levels in the hippocampus and restores cognitive impairment in chronic cerebral hypoperfused rats. Curr Neurovasc Res 7:268–280

    Article  CAS  PubMed  Google Scholar 

  13. Sakakima H, Khan M, Dhammu TS, Shunmugavel A, Yoshida Y, Singh I, Singh AK (2012) Stimulation of functional recovery via the mechanisms of neurorepair by S-nitrosoglutathione and motor exercise in a rat model of transient cerebral ischemia and reperfusion. Restor Neurol Neurosci 30:383–396

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Lin JB, Zheng CJ, Zhang X, Chen J, Liao WJ, Wan Q (2015) Effects of tetramethylpyrazine on functional recovery and neuronal dendritic plasticity after experimental stroke. Evid Based Complement Alternat Med 2015:394926.

    PubMed  PubMed Central  Google Scholar 

  15. Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91

    Article  CAS  PubMed  Google Scholar 

  16. Jin Q, Cheng J, Liu Y, Wu J, Wang X, Wei S, Zhou X, Qin Z, Jia J, Zhen X (2014) Improvement of functional recovery by chronic metformin treatment is associated with enhanced alternative activation of microglia/macrophages and increased angiogenesis and neurogenesis following experimental stroke. Brain Behav Immun 40:131–142

    Article  CAS  PubMed  Google Scholar 

  17. Zvejniece L, Svalbe B, Liepinsh E, Pulks E, Dambrova M (2012) The sensorimotor and cognitive deficits in rats following 90- and 120-min transient occlusion of the middle cerebral artery. J Neurosci Methods 208:197–204

    Article  PubMed  Google Scholar 

  18. Ramos-Cejudo J, Gutiérrez-Fernández M, Otero-Ortega L, Rodríguez-Frutos B, Fuentes B, Vallejo-Cremades MT, Hernanz TN, Cerdán S, Díez-Tejedor E (2015) Brain-derived neurotrophic factor administration mediated oligodendrocyte differentiation and myelin formation in subcortical ischemic stroke. Stroke 46:221–228

    Article  CAS  PubMed  Google Scholar 

  19. Sakakima H, Yoshida Y, Kadomatsu K, Yuzawa Y, Matsuo S, Muramatsu T (2004) Midkine expression in rat spinal motor neurons following sciatic nerve injury. Brain Res Dev Brain Res 153:251–260

    Article  CAS  PubMed  Google Scholar 

  20. Krafft PR, Altay O, Rolland WB, Duris K, Lekic T, Tang J, Zhang JH (2012) α7 nicotinic acetylcholine receptor agonism confers neuroprotection through GSK-3β inhibition in a mouse model of intracerebral hemorrhage. Stroke 43:844–850

    Article  CAS  PubMed  Google Scholar 

  21. Meng FT, Zhao J, Ni RJ, Fang H, Zhang LF, Zhang Z, Liu YJ (2015) Beneficial effects of enriched environment on behaviors were correlated with decreased estrogen and increased BDNF in the hippocampus of male mice. Neuro Endocrinol Lett 36:490–497

    PubMed  Google Scholar 

  22. Dahlqvist P, Rönnbäck A, Risedal A, Nergårdh R, Johansson IM, Seckl JR, Johansson BB, Olsson T (2003) Effects of postischemic environment on transcription factor and serotonin receptor expression after permanent focal cortical ischemia in rats. Neuroscience 119:643–652

    Article  CAS  PubMed  Google Scholar 

  23. Karelina K, Norman GJ, Zhang N, DeVries AC (2009) Social contact influences histological and behavioral outcomes following cerebral ischemia. Exp Neurol 220:276–282

    Article  PubMed  Google Scholar 

  24. Craft TK, Glasper ER, McCullough L, Zhang N, Sugo N, Otsuka T, Hurn PD, DeVries AC (2005) Social interaction improves experimental stroke outcome. Stroke 36:2006–2011

    Article  PubMed  Google Scholar 

  25. Nilsson M, Pekny M (2007) Enriched environment and astrocytes in central nervous system regeneration. J Rehabil Med 39:345–352

    Article  PubMed  Google Scholar 

  26. de Pablo Y, Nilsson M, Pekna M, Pekny M (2013) Intermediate filaments are important for astrocyte response to oxidative stress induced by oxygen-glucose deprivation and reperfusion. Histochem Cell Biol 140:81–91

    Article  PubMed  Google Scholar 

  27. Keiner S, Wurm F, Kunze A, Witte OW, Redecker C (2008) Rehabilitative therapies differentially alter proliferation and survival of glial cell populations in the perilesional zone of cortical infarcts. Glia 56:516–527

    Article  PubMed  Google Scholar 

  28. Lee SU, Kim DY, Park SH, Choi DH, Park HW, Han TR (2009) Mild to moderate early exercise promotes recovery from cerebral ischemia in rats. Can J Neurol Sci 36:443–449

    Article  PubMed  Google Scholar 

  29. Sirevaag AM, Greenough WT (1991) Plasticity of GFAP-immunoreactive astrocyte size and number in visual cortex of rats reared in complex environments. Brain Res 540:273–278

    Article  CAS  PubMed  Google Scholar 

  30. Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI (2013) Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiol Dis 54:252–263

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lan X, Zhang M, Yang W, Zheng Z, Wu Y, Zeng Q, Liu S, Liu K, Li G (2014) Effect of treadmill exercise on 5-HT, 5-HT1A receptor and brain derived neurophic factor in rats after permanent middle cerebral artery occlusion. Neurol Sci 35:761–766

    Article  PubMed  Google Scholar 

  32. Chen Y, Zhang J, Deng M (2015) Furin mediates brain-derived neurotrophic factor upregulation in cultured rat astrocytes exposed to oxygen-glucose deprivation. J Neurosci Res 93:189–194

    Article  CAS  PubMed  Google Scholar 

  33. Chen MR, Dai P, Wang SF, Song SH, Wang HP, Zhao Y, Wang TH, Liu J (2016) BDNF Overexpression Exhibited Bilateral Effect on Neural Behavior in SCT Mice Associated with AKT Signal Pathway. Neurochem Res 41:2585–2597

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (No. 81173315). We would like to thank the technical assistance given by National Center for Magnetic Resonance in Wuhan, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences.

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Correspondence to Weijing Liao or Qi Wan.

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Xiuping Chen and Xin Zhang have contributed equally to this work.

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Chen, X., Zhang, X., Liao, W. et al. Effect of Physical and Social Components of Enriched Environment on Astrocytes Proliferation in Rats After Cerebral Ischemia/Reperfusion Injury. Neurochem Res 42, 1308–1316 (2017). https://doi.org/10.1007/s11064-016-2172-x

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  • DOI: https://doi.org/10.1007/s11064-016-2172-x

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