Vitamin E prevents apoptosis in hippocampal neurons caused by cerebral ischemia and reperfusion in stroke-prone spontaneously hypertensive rats

Cerebral ischemia followed by oxygen reperfusion induced apoptosis in hippo campal neurons in stroke-prone spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats. Oxygen radicals were involved in reoxygenation in jury after hypoxia in hippocampal slices. Vitamin E inhibited the reoxygena tion injury in cultured cortical neurons. In addition, the temporal cortice s in Alzheimer's disease have increased sensitivity to oxygen radicals, and Vitamin E slowed the progression of the disease. Thus we fed Wistar Kyoto and SHRSP rats either a normal diet or a high Vitamin E diet for 3 weeks. W e measured Vitamin E concentrations of plasma and brain by applying the HPL C method. Vitamin E increased its concentration in plasma, cerebral cortex, and hippocampus (p < 0.01) during a 3-week pretreatment. In addition, we c lipped both common carotid arteries in these rats for 30 minutes. After the blocking, the rats were reperfused for 6 and 9 days, respectively, and the n killed. We cut the brains coronally, removed the hippocampal CA1 regions, and examined the neurons using an electron microscope. SHRSP rats with nor mal cerebral circulation had 30.4 +/- 8.0 apoptotic neurons per 1000 neuron s. Cerebral ischemia followed by 6 and 9 days of reperfusion, respectively, increased apoptotic neurons in SHRSP rats fed a normal diet (6 days: 542.5 +/- 154.1 per 1000 neurons; 9 days: 657.5 +/- 110.2 per 1000 neurons). In contrast, apoptopic neurons in SHRSP rats fed a high Vitamin E diet were si gnificantly (p < 0.01) small in number (6 days: 41.3 +/- 27.5 per 1000 neur ons; 9 days: 35.5 +/- 19.7 per 1000 neurons) even though the rats were trea ted in the same way. These data demonstrate that oxygen radical generation occurs after reperfusion and that free radicals heavily damage the neurons in SHRSP rats. Vitamin E reacts with the radicals and prevents neuronal apo ptosis caused by cerebral ischemia and reperfusion. Therefore, Vitamin E se ems to be an important agent in lowering radical damage to hippocampal neur ons.