[Effects of idebenone (CV-2619) on neurological deficits, local cerebral blood flow, and energy metabolism in rats with experimental cerebral ischemia]

Abstract

Improvement of energy metabolism in ischemic cerebral tissue benefits the therapy of occlusive cerebrovascular lesions. In the present study, the effects of 6-(10-hydroxydecyl)-2, 3-dimethoxy-5-methyl-1, 4-benzoquinone (idebenone, CV-2619) on neurological signs, local cerebral blood flow, and cerebral energy metabolism were assessed in stroke-prone spontaneously hypertensive rats (SHRSP) with bilateral carotid artery occlusion (BCAO). Pretreatment with CV-2619 (10-100 mg/kg, p.o.) for three or ten successive days delayed the onset of ischemic seizure (acute stroke) and prolonged survival time in the SHRSP. When the compound (100 mg/kg, i.p.) was given once 30 min after BCAO, it exerted similar ameliorating effects on the neurological deficits. When CV-2619 (100 mg/kg for 3 days) was given orally, it did not inhibit a decrease in regional cerebral blood flow induced by the carotid artery occlusion. However, the same treatment markedly inhibited increases in lactate content and lactate/pyruvate ratio and a decrease in ATP content in the cerebral cortex. In addition, the compound showed no effect on cerebral blood flow in normal rats. These results suggest that CV-2619 has an ameliorating effect on neurological deficits related with cerebral ischemia, and this effect is mediated by improved cerebral energy metabolism.