N-TERT-BUTYL-ALPHA-PHENYLNITRONE IMPROVES RECOVERY OF BRAIN ENERGY-STATE IN RATS FOLLOWING TRANSIENT FOCAL ISCHEMIA
N-TERT-BUTYL-ALPHA-PHENYLNITRONE IMPROVES RECOVERY OF BRAIN ENERGY-STATE IN RATS FOLLOWING TRANSIENT FOCAL ISCHEMIA
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DOI：
10.1073/pnas.92.11.5057
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发表时间：
1995-05-23
影响因子：
11.1
通讯作者：
SIESJO, BK
中科院分区：
文献类型：
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作者：
FOLBERGROVA, J;ZHAO, Q;SIESJO, BK
最近的研究结果表明，自旋捕获剂N-叔丁基-α-苯基硝酮（PBN）可减少大脑中动脉闭塞（MCAO）引起的梗死面积，即使是在缺血后给药。本研究的目的是探讨PEN是否影响能量代谢的恢复。通过管腔内细丝技术在大鼠中诱导2小时持续时间的MCAO。在缺血结束时和再循环1、2和4小时后，将脑原位冷冻。再循环后1小时给予PEN。对新皮质局灶和局灶周围（“半影”）区域进行采样，用于磷酸肌酸（PCr）分析。肌酸、ATP、ADP、AMP、糖原、葡萄糖和乳酸。缺血2小时后，半暗带显示中度至显著降低，病灶显示PCr和ATP浓度显著降低，腺嘌呤核苷酸总和下降，糖原几乎耗尽，乳酸浓度增加。再循环1小时导致能量状态仅部分恢复，2小时后几乎没有进一步改善，4小时后出现二次恶化的迹象，特别是在病灶中。经过4小时的再循环，PBN治疗的动物表现出显着的能量状态的恢复，与ATP和乳酸含量的焦点和半影接近正常值。虽然不能排除PEN对线粒体的影响，但结果表明PEN通过防止微循环的逐渐损害而起作用。这些结果证明了对目前关于局灶性缺血性损伤病理生理学观点的重新评估，并表明卒中存在许多小时的治疗窗口。
Recent results have demonstrated that the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) reduces infarct size due to middle cerebral artery occlusion (MCAO), even when given after ischemia. The objective of the present study was to explore whether PEN influences recovery of energy metabolism. MCAO of 2-hr duration was induced in rats by an intraluminal filament technique. Brains were frozen in situ at the end of ischemia and after 1, 2, and 4 hr of recirculation. PEN was given 1 hr after recirculation. Neocortical focal and perifocal (''penumbra'') areas were sampled for analyses of phosphocreatine (PCr). Creatine, ATP, ADP, AMP, glycogen, glucose, and lactate. The penumbra showed a moderate-to-marked decrease and the focus showed a marked decrease in PCr and ATP concentrations, a decline in the sum of adenine nucleotides, near-depletion df glycogen, and an increase in lactate concentration after 2 hr of ischemia. Recirculation for 1 hr led to only a partial recovery of energy state, with little further improvement after 2 hr and signs of secondary deterioration after 4 hr, particularly in the focus. After 4 hr of recirculation, PBN-treated animals showed pronounced recovery of energy state, with ATP and lactate contents in both focus and penumbra approaching normal values. Although an effect of PEN on mitochondria cannot be excluded, the results suggest that PEN acts by preventing a gradual compromise of microcirculation. The results justify a reevaluation of current views on the pathophysiology of focal ischemic damage and suggest that a therapeutic window of many hours exists in stroke.