Immunoreactivity of cyclin D1/cdk4 in neurons and oligodendrocytes after focal cerebral ischemia in rat.

We investigated the expression of cyclin D1 and its kinase, cdk4, after induction of focal cerebral ischemia in the rat. Brain from rats (n = 6) subjected to 2 hours of transient middle cerebral artery occlusion and 46 hours of reperfusion, and control sham-operated (n = 3) and normal (n = 2) rats were processed for dual label immunohistochemical study for cellular identification of the expression of these cell cycle proteins. Antibodies raised against microtubule-associated protein 2 and neuronal specific enolase for neurons, glial fibrillary acidic protein for astrocytes, myelin basic protein for oligodendrocytes and lectin histochemical study with the B4-isolectin for microglia were used for cell type identification. Double staining for DNA fragmentation detection (TUNEL) and expression of cyclin D1 and cdk4 also was performed. Cyclin D1 and cdk4 were selectively expressed in morphologically intact or altered neurons and oligodendrocytes localized to the ischemic tissue. Apoptotic cells were not immunoreactive to cyclin D1 and cdk4 at 46 hours after 2 hours of middle cerebral artery occlusion. The selective expression of cell cycle proteins observed in nonapoptotic ischemic postmitotic neurons and oligodendrocytes suggests a role for these proteins in cell survival after transient focal cerebral ischemia.