Brain-Derived Neurotrophic Factor (BDNF) As a Regulator of Apoptosis under Conditions of Focal Experimental Stroke.

ABSTRACT

The immunolocalization of apoptotic factors in rat neocortex was studied on the model of permanent occlusion of the middle cerebral artery with administration of exogenous BDNF. We revealed heterogeneous distribution of pro- and anti-apoptotic factors in the stroke area and in the surrounding penumbra, where caspase-3+ and p53+ cells were found. Their number was maximum on day 3 of ischemia. The number of neurons containing anti-apoptotic factors was relatively decreased. Injection of BDNF changed the distribution of apoptotic factors. In the penumbra area, BDNF enhanced the expression of Mdm2 primarily in the pyramid cells of layers V/VI and Bcl-2 in interneurons of layers II and III. Localization of p53 and caspase-3 varied at different terms of the ischemic period and showed an inverse dependence. Considering the selective neuroprotective effect of BDNF, various mechanisms of the formation of ischemic tolerance in neurons are proposed.