The effects of retinoic acid on the expression of neurogranin after experimental cerebral ischemia

Retinoic acid (RA) is an active metabolite of Vitamin A, and plays an important role in the normal development of the central nervous system. Neurogranin (NG) is a brain-specific postsynaptic kinase C (PKC) substrate and calmodulin-binding protein. The effects of RA-NG interaction on ischemic brain injuries are still unclear. We investigated the effects of exogenous RA on cerebral ischemia, the involvement of NG after distal middle cerebral artery occlusion (dMCAO), and the mechanism of RA neuroprotection in rats. Focal cortical infarction was developed in the dMCAO model, followed by intraperitoneal treatment with either vehicle or RA; then the rats were evaluated with neurological deficit scores according to a beam-walking test. The infarction volume was analyzed in hematoxylin and eosin (HE)stained sections; NG mRNA expression level was measured with a real-time PCR; and NG protein expression was determined immunohistochemically at 3, 7, 14, 21 and 28 days after dMCAO. The RA-treated rats showed a significant improvement in functional deficits and a significant decrease in infarct volume after dMCAO, compared with the vehicle group. The RA group showed an increase in NG protein or mRNA expression, compared with the vehicle group. In conclusion, administration of RA decreased the infarct volume, and promoted neurological functional recovery. This neuroprotective effect is attributed, at least in part, to NG mRNA and NG protein expression. (c) 2008 Elsevier B.V. All rights reserved.