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Vitamin
E prevents Apoptosis in Hippocampal Neurons caused by Cerebral Ischemia
and Reperfusion in Stroke-Prone Spontaneously Hypertensive Rats |
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Motoki Tagami,
Katsumi Ikeda, Kazuo Yamagata, Yasuo Nara, Hideaki Fujino, Akiyoshi Kubota,
Fujio Numano, and Yukio Yamori |
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Department
of Internal Medicine (MT, HF, AK), SANRAKU Hospital, Chiyoda-ku, Tokyo,
Department of Food Industrial Science (KY, YN), Toa University, Shimonoseki-shi,
Yamaguchi, Department of Internal Medicine (FN), Tokyo Medical and Dental
University, Bunkyo-ku, Tokyo, and Graduate School of Human and Environmental
Studies (KI, YY), Kyoto University, Kyoto, Japa |
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Cerebral ischemia followed
by oxygen reperfusion induced apoptosis in hippocampal neurons in stroke-prone
spontaneously hypertensive rats (SHRSP) but not in Wistar Kyoto rats. Oxygen
radicals were involved in reoxygenation injury after hypoxia in hippocampal
slices. Vitamin E inhibited the reoxygenation injury in cultured cortical
neurons. In addition, the temporal cortices 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. We measured Vitamin E concentrations
of plasma and brain by applying the HPLC method. Vitamin E increased its
concentration in plasma, cerebral cortex, and hippocampus (p <
0.01) during a 3-week pretreatment. In addition, we clipped both common
carotid arteries in these rats for 30 minutes. After the blocking, the rats
were reperfused for 6 and 9 days, respectively, and then killed. We cut
the brains coronally, removed the hippocampal CA1 regions, and examined
the neurons using an electron microscope. SHRSP rats with normal cerebral
circulation had 30.4 +/- 8.0 apoptotic neurons per 1000 neurons. 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,
apoptotic neurons in SHRSP rats fed a high Vitamin E diet were significantly
(p < 0.01) small in number (6 days: 41.3 +/- 27.5 per 1000 neurons;
9 days: 35.5 +/- 19.7 per 1000 neurons) even though the rats were treated
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 apoptosis
caused by cerebral ischemia and reperfusion. Therefore, Vitamin E seems
to be an important agent in lowering radical damage to hippocampal neurons.
(Lab Invest, 79:609-615) |
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