Pretreatment with the AT1 receptor antagonist irbesartan significantly improved neurological outcome and reduced c-Fos and c-Jun expression after focal cerebral ischemia in rats.
Does central AT1 receptor blockade with irbesartan improve neurological outcome and reduce AP-1 transcription factor expression after focal brain ischemia in rats?
Long-term blockade of central AT1 receptors with irbesartan improves recovery and reduces neurodegeneration-associated protein expression after focal brain ischemia in rats.
BACKGROUND AND PURPOSE: Angiotensin-converting enzyme inhibitors have been shown to protect against stroke in hypertensive rats and to improve neurological outcome after cerebral ischemia in normotensive rats. The present study was designated to test the hypothesis that blockade of brain AT(1) receptors improves the recovery from focal cerebral ischemia and reduces expression of AP-1 transcription factors c-Fos and c-Jun, which have been associated with programmed cell death and neurodegeneration. METHODS: Experiments were carried out in normotensive male Wistar rats. Focal cerebral ischemia was induced by middle cerebral artery occlusion lasting for 90 minutes and followed by reperfusion. The selective AT(1) receptor antagonist irbesartan was infused intracerebroventricularly over a 5-day period before the induction of ischemia at a dose that inhibited brain but not vascular AT(1) receptors. Twenty-four hours after ischemia, neurological outcome was evaluated and expression of c-Fos and c-Jun proteins in the brain was studied immunocytochemically. RESULTS: Focal brain ischemia resulted in a strong induction of c-Fos and c-Jun proteins in the cortex, which positively correlated with the degree of neurological deficits. Treatment of rats with irbesartan significantly improved neurological outcome of focal cerebral ischemia when compared with the vehicle-treated group and markedly reduced the expression of c-Fos and c-Jun proteins in the cortex on the ligated side of the brain. Irbesartan pretreatment completely abolished the ischemia-induced c-Fos expression in the hippocampus. CONCLUSIONS: The present study shows a relationship between c-Fos and c-Jun expression and neurological outcome after focal brain ischemia. Our data indicate that long-term blockade of central AT(1) receptors improves the recovery from brain ischemia and reduces the expression of c-Fos and c-Jun proteins in the brain. Pretreatment with an AT(1) receptor antagonist has beneficial effects after cerebral ischemia.
Dai et al. (Mon,) conducted a other in Focal cerebral ischemia. Irbesartan vs. Vehicle was evaluated on Neurological outcome and expression of c-Fos and c-Jun proteins in the brain 24 hours after ischemia. Pretreatment with the AT1 receptor antagonist irbesartan significantly improved neurological outcome and reduced c-Fos and c-Jun expression after focal cerebral ischemia in rats.