gms | German Medical Science

The AT1 receptor antagonist, candesartan, exerts neuroprotective actions when administered peripherally and centrally before the onset of ischemia. The present study investigated whether candesartan can improve the recovery from stroke when administered after focal ischemia. Candesartan was administered systemically at a low dose of 0.3 mg/kg, which has been shown to effectively block AT1 receptors within the brain with negligible effect on blood pressure.

Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion. Cerebral blood flow was monitored by laser Doppler flowmetry. Only rats with a reduction of the ipsilateral cerebral blood flow of >75% were included in the study. Candesartan was injected subcutaneously 3 h after the onset of MCAO and then once daily on 2 consecutive days. Control animals received vehicle. Blood parameters were assessed before, during and after MCAO. Neurological scores were examined 24 and 48 hours after MCAO. Two days after MCAO, the brains were removed for the determination of infarct volume by cresyl violet staining and for immunhistochemical evaluation of apoptosis using TUNEL-staining.

Treatment with candesarten did not alter cerebral blood flow or blood parameters. Neurological scores were significantly better in rats treated with candesartan at 24 and 48 hours after ischemia. Infarct volume was reduced by 63% in rats treated with candesarten 48 hours after ischemia as compared to vehicle-treated rats. Candesartan significantly decreased the ischemia-induced TUNEL staining in the penumbra of the ischemic cortex.

The present study demonstrates that peripheral treatment with candesartan at a low dose starting 3 h after focal cerebral ischemia improved neurological outcome and reduced infarct volume. Anti-apoptotic mechanisms may be involved in the candersartan-induced neuroprotective effects.