Transforming growth factor -α Improves memory impairment and neurogenesis following ischemia reperfusion

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-α) 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-α 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-α injection significantly increased nestin expression in both the hippocampal
DG and SVZ areas. TGF-α 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-α treatment.
Conclusion: Our findings proved that TGF-α reduced ischemic injury and played a
neuroprotective role in the pathogenesis of ischemic injury