Effects of glucocorticoid and glucocorticoid receptors on stress-induced neurogenesis suppression

Studies have shown that cerebral ischemia activates neurogenesis and that stress inhibits neurogenesis. However, the role of stress hormone levels on neurogenesis following cerebral ischemia remains poorly understood. The present study explored the possible regulatory mechanisms of adult neurogenesis under pathological conditions by examining changes and regulation of glucocorticoid receptors in adult rats subjected to transient unilateral middle cerebral artery suture occlusion. Corticosterone levels gradually increased following middle cerebral artery occlusion, and the number of glucocorticoid receptor-positive cells decreased. The number of 5-bromodeoxyuridine- and nestin-positive cells significantly increased at 1 and 2 weeks after ischemia. A large number of doublecortin-positive cells migrated from the hippocampus to the cortex. At 3 weeks post-surgery, the number of 5-bromodeoxyuridine- and nestin-positive cells significantly reduced in the subventricular zone. Increased corticosterone levels decreased vascular endothelial cell proliferation and neurogenesis, and the number of glucocorticoid receptor-positive cells decreased. In the sham surgery group, vascular endothelial cell proliferation related to post-ischemic cerebral rehabilitation was not detected. Corticosterone levels increased, but the number and distribution of glucocorticoid receptor-positive cells were not changed. However, normal neurogenesis and migration of neural stem cells existed in the adult rat brain in the sham surgery group. Results suggested that glucocorticoid receptors influenced neurogenesis and were negatively regulated by glucocorticoid levels following focal cerebral ischemia and reperfusion.