一過性脳虚血障害におけるＴＨＡＭ（アルカリ化剤）の効果に関する実験的検討

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  • Effect of alkalizing agents on focal cerebral ischemia by temporary middle cerebral artery occlusion in rats.

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Metabolic acidosis in cerebral ischemia is considered deleterious to cell function. Amelioration of systemic and focal cerebral acidosis by an alkalizing agent could reduce ischemic brain damage. We investigated the effect of tromethamine (TRAM) on focal cerebral ischemia by temporary middle cerebral artery occlusion in rats. 45 male Wistar rats were intubated and ventilated with 0.8% halothane and a mixture of 70% NO2 and 30% O2. The animals were subjected to middle cerebral artery (MCA) occlusion by inserting a 4-0 nylon monofilament into the proximal MCA. Recirculation was performed by removal of the thread from the internal carotid artery. All rats were subjected to 2 hours of MCA occlusion followed by 2 hours of reperfusion. In the control group, physiological saline was continuously infused. The THAM group received continuous administration of 0.3 M THAM (2 ml/kg/hr). The brain water content was measured by the specific gravimetric method. The regional changes in brain tissue pH and infarction volume were estimated by the umbelliferone method and TTC staining, respectively. In the control group, the brain water content of the infarct area was significantly increased. However, in the THAM group, the water content showed no significant change in one part of the parietal cortex on the lesion side. The brain regional pH in the control group was significantly decreased in the infarct area. In the THAM group, the regional pH was markedly increased in the peripheral lesion of the ischemic area, although the regional pH was decreased in the center of the ischemic lesion. The volume of acidotic lesion was significantly reduced in the THAM group. The size of the infarct area was significantly decreased from 16.29 ± 16.19% in the control group to 0.78 ± 1.03% in the TRAM group. These findings suggest that THAM can improve intracellular acidosis in the periinfarct area at the acute phase of MCA occlusion, leading to improvement of brain edema. Normalization of systemic acidosis with THAM was effective for reducing brain edema and infarct size at the early stage of temporary cerebral ischemia.

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  • 脳卒中

    脳卒中 20 (4), 375-382, 1998

    一般社団法人 日本脳卒中学会

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