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

• DOI: 10.1016/j.brainres.2014.06.031
• Publication Date: 2014-07-02T10:04:39Z
• Authors: Dashi Qi; Changjie Ouyang; Yulan Wang; Shichun Zhang; Xijuan Ma; YuanJian Song; HongLi Yu; Jiali Tang; Wei Fu; Lei Sheng; Lihua Yang; Mei Wang; Weihao Zhang; Lei Miao; Tengteng Li; Xiaojing Huang; Hongyan Dong
• Keywords: Male; Neurons; 0301 basic medicine; Caspase 3; Brain-Derived Neurotrophic Factor; Carbazoles; Apoptosis; Transfection; Brain Ischemia; Indole Alkaloids; Rats, Sprague-Dawley; Stroke; Disease Models, Animal; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Heme Oxygenase (Decyclizing); Animals; Receptor, trkB; Enzyme Inhibitors; CA1 Region, Hippocampal; Proto-Oncogene Proteins c-akt; Signal Transduction

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.