Time course of cerebral hypoperfusion-induced neurodegenerative changes in the cortex of male and female rats.

ABSTRACT

To study time-dependent and gender-specific intracellular and biochemical mechanisms that lead to neurodegeneration due to moderate but persistent reduction of cerebral blood flow, adult male and female Wistar rats were divided into two main groups - controls that underwent sham operation and animals subjected to permanent bilateral occlusion of common carotid arteries. Animals were sacrificed 3, 7 or 90 days following the insult. Expression of several apoptotic proteins in synaptic fractions along with Fluoro-Jade B staining and DNA fragmentation assay were used to estimate the apoptotic processes and potential neurodegeneration in cerebral cortex. Data suggest a time-specific increase of Bax as well as time- and gender-associated downregulation in protein expression of Bcl-2, up-regulation of procaspase 3, accompanied with increased cleavage of procaspase 3 and PARP in synaptic terminals. Furthermore, time- but not gender-specific neurodegeneration was observed. Our findings support the concept of time- and gender-associated response to permanent bilateral occlusion of common carotid arteries, which would enable better understanding of the mechanisms underlying cerebral hypoperfusion.