NEURONAL VULNERABILITY OF STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS TO ISCHEMIA AND ITS PREVENTION WITH ANTIOXIDANTS SUCH AS VITAMIN E

Stroke-prone spontaneously hypertensive rats (SHRSP/lzm) develop severe hypertension, and more than 95% of them die of cerebral stroke. Hypoxic stimulation followed by oxygen reperfusion induces neuronal damage in both normotensive Wistar Kyoto/lzm (WKY/lzm) and SHRSP/lzm rats, and the percentage of neurons that undergo apoptosis during hypoxia-reperfusion is markedly higher in SHRSP/lzm rats than in WKY/lzm rats. The biochemical characteristics of the SHRSP/lzm rats, unlike those of WKY/lzm rats, might act as a factor in the stroke proneness of SHRSP/lzm rats. In the hippocampus, the formation of hydroxyl radicals and the cerebral blood flow-independent formation of nitric oxide (NO) were strongly increased after reperfusion in SHRSP/lzm rats, and the neuronal expression of the thioredoxin and Bcl-2 genes was significantly decreased in the SHRSP/lzm rats compared with the WKY/lzm rats. On the other hand, the effects of antioxidants against neuronal death associated with cerebral ischemia-reperfusion were stronger in the SHRSP/lzm rats, in which the addition of vitamin E or ebselen almost completely inhibited neuronal death. Namely, the addition of 100 mu g/ml of vitamin E under hypoxia/reoxygenation (H/R) conditions completely inhibited WKY and SHRSP/lzm neuronal death. Vitamin E exerts a marked inhibitory effect against neuronal damage via its incorporation into mitochondrial membranes, where it captures reactive oxygen and free radicals. The susceptibility of neurons to apoptosis in SHRSP/lzm rats is partly due to an insufficiency of mitochondrial redox regulation and apoptosis-inhibitory proteins. In this review, we describe the neuronal vulnerability of SHRSP/lzm rats induced by cerebral ischemia and the effects of antioxidants such as vitamin E. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.