Transforming Growth Factor -α Improves Memory Impairment and Neurogenesis Following Ischemia Reperfusion

Objective: Stroke is most important cause of death and disability in adults. The hippocampal CA1 and sub-ventricular zone neurons are vulnerable to ischemia that can impair memory and learning functions. Although neurogenesis normally occurs in the dentate gyrus (DG) of the hippocampus and sub-ventricular zone (SVZ) following brain damage, this response is unable to compensate for severely damaged areas. This study aims to assess both neurogenesis and the neuroprotective effects of transforming growth factor-alpha (TGF-alpha) on the hippocampus and SVZ following ischemia-reperfusion. Materials and Methods: In this experimental study, a total of 48 male Wistar rats were divided into the following groups: surgical (n=12), phosphate buffered saline (PBS) treated vehicle shams (n=12), ischemia (n=12) and treatment (n=12) groups. Ischemia was induced by common carotid occlusion for 30 minutes followed by reperfusion, and TGF-alpha was then injected into the right lateral ventricle. Spatial memory was assessed using Morris water maze (MWM). Nestin and Bcl-2 family protein expressions were studied by immunohistochemistry (IHC) and Western blot methods, respectively. Finally, data were analyzed using Statistical Package for the Social Sciences (SPSS, SPSS Inc., Chicago, USA) version 16 and one-way analysis of variance (ANOVA). Results: TGF-alpha injection significantly increased nestin expression in both the hippocampal DG and SVZ areas. TGF-alpha treatment caused a significant decrease in Bax expression and an increase in Bcl-2 anti-apoptotic protein expression in the hippocampus. Our results showed a significant increase in the number of pyramidal neurons. Memory also improved significantly following TGF-alpha treatment. Conclusion: Our findings proved that TGF-alpha reduced ischemic injury and played a neur-oprotective role in the pathogenesis of ischemic injury.