Involvement Of Cyclin-Dependent Kinase-5 In Early Brain Injury After Experimental Subarachnoid Hemorrhage

Background:Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase (CDK) family, is characterized as a key mediator of neuronal death and survival. Although Cdk5 was implicated in a number of neurological disorders, the role of Cdk5 in early brain injury (EBI) after subarachnoid hemorrhage (SAH) remains unclear. In the present study, we studied the involvement of Cdk5 in the pathogenesis of EBI after SAH.Methods:First, we determined time course of Cdk5, Cdk5-pTyrl5 and p25 expressions in rat cortex after SAH. After the induction of SAH, the rats were randomly divided into five groups and killed at 6 h,12 h, and on day 1, day 3, day 5 post-SAH (n=6 for each group). Another 6 rats were sacrificed to detect the localization of Cdk5 by immunof luorescence assay on day 1. Sham operated rats (n=12) were injected with equal volumes of 0.9% saline solution according to the same procedure.Secondly, we explored the role of Cdk5 in brain injury following SAH. Rats were randomly distributed into four groups:sham+vehicle group (n = 24), subjected to the SAH procedure except for injection with equal volumes of 0.9% saline solution into the prechiasmatic cistern, and received 20% DMSO as the vehicle; SAH+vehicle group (n= 24), subjected to SAH and treated with the same volume of vehicle as the sham+vehicle group; SAH+Roscovitine(50?g) group (n= 24), subjected to SAH and treated with 50?g roscovitine; SAH+Roscovitine (100?g) group (n= 24), subjected to SAH and treated with 100?g roscovitine.Results:Our results demonstrated that SAH introduced an increase of Cdk5, p25 and Cdk5-pTyr15 expressions in the rat cortex. Immunofluorescence staining indicated that Cdk5 was expressed in neuron and astrocyte of rat cortex after SAH, with evidence of nuclear translocation in neurons. Moreover, administration of roscovitine effectively reduced apoptotic cell, alleviated brain edema, and improved cortical neuron survival. Conclusion:Our study provided convincing evidence that cdk5 might be activated in the rat brain after SAH. Moreover,intracisternal administration of roscovitine conferred significant neuro-protection and effectively reduced apoptotic cell after experimental SAH.