The effects of cyclin-dependent kinase inhibitor on reactive gliosis of the ipsilateral cortex following MCA occlusion

Objective Functional significance of reactive gliosis may be beneficial or harmful for neuronal survival and regeneration after central nervous system (CNS) injupy.Cyclin-dependent kinases (CDKs) are commonly known to regulate cell proliferation. The present study aimed to determine whether the addition of CDK inhibitor could reduce astrocyte proliferation as well as limit progressive glial scar.Methods Ischemia/reperfusion injury was induced by temporary middle cerebral artery occlusion (MCAO). Olomoucine (4 mg/kg) was admincstered 3 and 5 days after MCAO. Four weeks post-injury, all rats were killed. Their brains were sectioned and sections were stained with HE. In the cortex ipsilateral to the side of MCAO, the expression level of glial fibrillary acidic protein (GFAP) was analyzed by Western blot and the localization of GFAP was assessed by immunohistochemistry.Results All brains with temporary MCAO(4 weeks) had cavitation surrounded by glial scar tissue. Astrocytes appeared hypertrophic, with higher density near the glial scarring regions of the ipsilateral cortex.Application of olomoucine could reduce cortical cavitation (P0.05) and partially inhibitthe astrocyte proliferative response. Western blot analysis from the ipsilateral cortex extractsof olomoucine treated animals also revealed a decrease of GFAP expression after 4 weeks of MCAO compared with control animals (P0.05).Conclusion These results suggest the hypothesis that, by reducing glial proliferation, CDK inhibitor may help create an environment that is more suitable for neuronal survival and regeneration.