Neuroprotection Induced by Transplanted CDK5 Knockdown Astrocytes in Global Cerebral Ischemic Rats.

Abstract

Cerebral ischemia is a cerebrovascular episode that generates a high incidence of death and physical and mental disabilities worldwide. Excitotoxicity, release of free radicals, and exacerbated immune response cause serious complications in motor and cognitive areas during both short and long time frames post-ischemia. CDK5 is a kinase that is widely involved in the functions of neurons and astrocytes, and its over-activation is implicated in neurodegenerative processes. In this study, we evaluated the brain parenchymal response to the transplantation of CDK5-knockdown astrocytes into the somatosensory cortex after ischemia in rats. Male Wistar rats were subjected to the two-vessel occlusion (2VO) model of global cerebral ischemia and immediately transplanted with shCDK5miR- or shSCRmiR-transduced astrocytes or with untransduced astrocytes (Control). Our findings showed that animals transplanted with shCDK5miR astrocytes recovered motor and neurological performance better than with those transplanted with WT or shSCRmiR astrocytes. Cell transplantation produced an overall prevention of neuronal loss, and CDK5-knockdown astrocytes significantly increased the immunoreactivity (IR) of endogenous GFAP in branches surrounding blood vessels, accompanied by the upregulation of PECAM-1 IR in the walls of vessels in the motor and somatosensory regions and by an increase in Ki67 IR in the subventricular zone (SVZ), partially associated with the production of BDNF. Together, our data suggest that transplantation of shCDK5miR astrocytes protects the neurovascular unit in ischemic rats, allowing the motor and neurological function recovery.