HO-1 attenuates hippocampal neurons injury via the activation of BDNF–TrkB–PI3K/Akt signaling pathway in stroke

Abstract Although recent studies have found that HO-1 plays an important role in neuronal survival, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of HO-1 against is...

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Veröffentlicht in:Brain research 2014-08, Vol.1577, p.69-76
Hauptverfasser: Qi, Dashi, Ouyang, Changjie, Wang, Yulan, Zhang, Shichun, Ma, Xijuan, Song, YuanJian, Yu, HongLi, Tang, Jiali, Fu, Wei, Sheng, Lei, Yang, Lihua, Wang, Mei, Zhang, Weihao, Miao, Lei, Li, Tengteng, Huang, Xiaojing, Dong, Hongyan
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Sprache:eng
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Zusammenfassung:Abstract Although recent studies have found that HO-1 plays an important role in neuronal survival, little is known about the precise mechanisms occurring during cerebral ischemia/reperfusion (I/R). Therefore, the aim of this study was to investigate the neuroprotective mechanisms of HO-1 against ischemic brain injury induced by cerebral I/R and to explore whether the BDNF–TrkB–PI3K/Akt signaling pathway contributed to the protection provided by HO-1. Over-expressed HO-1 plasmids were employed to induce the overexpression of HO-1 through hippocampi CA1 injection 5 days before the cerebral I/R animal model was induced by four-vessel occlusion for 15 min transient ischemia and followed by reperfusion in Sprague-Dawley rats. Immunoblotting was carried out to examine the expression of the related proteins, and HE-staining was used to detect the percentage of living neurons in the hippocampal CA1 region. The results showed that over-expressed HO-1 could significantly protect neurons against cerebral I/R. Furthermore, the protein expression of BDNF, TrkB and p-Akt also increased in the rats treated with over-expressed HO-1 plasmids. However, treatment with tropomyosin receptor kinase B (TrkB) receptor antagonist (K252a) reversed the HO-1-induced increase in BDNF and p-Akt protein levels and decreased the level of cleaved caspase-3 protein in I/R rats. In summary, our results imply that HO-1 can decrease cell apoptosis in the I/R rat brain and that the mechanism may be related to the activation of the BDNF–TrkB–PI3K/Akt signaling pathway.
ISSN:0006-8993
1872-6240
DOI:10.1016/j.brainres.2014.06.031