Role of cyclin-dependent kinase 5 in early brain injury following experimental subarachnoid hemorrhage.

Abstract

Increasing evidence indicates that early brain injury (EBI) can contribute to poor outcomes following subarachnoid hemorrhage (SAH), and is associated with apoptosis. Cyclin-dependent kinase 5 (Cdk5) is a key mediator of neuronal viability. The role of Cdk5 in several neurological disorders has been elucidated; however, its role in EBI after SAH remains unclear. The present study aimed to explore the involvement of Cdk5 in EBI after SAH. The expression levels of Cdk5, Cdk5 phosphorylated at Tyr15 (Cdk5-pTyr15) and p25 (a Cdk5 activator) were assessed by western blotting, and the cell distribution of Cdk5 was demonstrated by double immunofluorescence. The expression levels of caspase-3 and cytochrome c were evaluated by western blotting to assess the severity of neuronal apoptosis. Nissl and TUNEL staining experiments were performed to observe the effects of roscovitine, a Cdk5 inhibitor, on EBI following SAH. The results indicated that the expression levels of Cdk5, p25 and Cdk5-pTyr15 significantly increased in the rat temporal cortex following SAH. Immunofluorescence staining indicated that Cdk5 was expressed in the neurons and astrocytes of the rat cortex after SAH and that Cdk5 underwent nuclear translocation in neurons. Roscovitine administration effectively inhibited Cdk5 activation. In conclusion, roscovitine treatment significantly mitigated EBI and alleviated cerebral edema following SAH. These findings suggest that Cdk5 is an important target in SAH therapy.