High doses of methamphetamine that cause disruption of the blood-brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus
High doses of methamphetamine that cause disruption of the blood-brain barrier in limbic regions produce extensive neuronal degeneration in mouse hippocampus
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DOI：
10.1002/syn.20324
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发表时间：
2006-12-01
期刊：
影响因子：
2.3
通讯作者：
Ali, Syed
中科院分区：
文献类型：
--
作者：
Bowyer, John F.;Ali, Syed
采用单次大剂量(40 mg/kg)D-甲基苯丙胺(METH)染毒后的脑组织学检查，以确定这种染毒常引起的血脑屏障(BBB)破坏、体温升高、剧烈惊厥活动和广泛变性之间的关系。在体温极高(体温>；40.5摄氏度)表现为癫痫持续状态的小鼠中，在接触冰毒后90分钟内，观察到杏仁内侧和腹侧的小鼠免疫球蛋白免疫反应性(IgGIR)增加。在少数情况下，体温在40.0摄氏度的范围内，这种IgGlR也可以在表现出癫痫持续状态的动物身上看到。与神经退行性变相关的IgGIR在12小时内也出现在海马区，这表明该区域的血脑屏障也发生了破坏。在冰毒后4h，首次在杏仁核和海马区检测到退化神经元，荧光素C(FJ-C)标记。动物杏仁核和海马锥体细胞区有广泛的神经变性，冰毒后12小时和24小时这些区域的IgGIR显著升高。24 h内可见脑内小胶质细胞迅速活化和/或巨噬细胞在IgGIR显著升高的区域内浸润，并伴有强烈的神经元变性，3天后海马神经元的吞噬速度非常快，几乎不存在FJ-C标记。在没有体温过高和癫痫发作的情况下，METH没有在边缘区域引起IgGIR增加或神经变性。因此，当体温过高时，高剂量的冰毒会对血脑屏障造成损害，导致快速而广泛的海马体和杏仁核损伤。杏仁内侧的血脑屏障破坏首先发生，很可能与癫痫的诱发和严重程度有关，而海马区的血脑屏障破坏可能是癫痫发作和体温过高的结果。这种海马体损伤应该足以损害学习和记忆。2006年出版，威利-利斯，lnc。
Histological examination of brain after a single high (40 mg/kg) dose Of D-methamphetamine (METH) was used to determine the relationships between blood-brain barrier (BBB) disruption, hyperthermia, intense seizure activity, and extensive degeneration that this exposure often produces. In very hyperthermic mice (body temperatures > 40.5 degrees C) exhibiting status epilepticus, increase in mouse IgG immunoreactivity (IgGIR) in the medial and ventral amygdala was observed within 90 min after METH exposure. In a few instances, where body temperature was in the 40.0 degrees C range, such IgGlR was also seen in animals that had exhibited status epilepticus. Variable increases in IgGIR, which correlated with neurodegeneration, also occurred within 12 h in the hippocampus, indicating BBB disruption in this region also. Degenerating neurons, Fluoro-Jade C (FJ-C) labeled, were first detected 4 h after METH in the amygdala and hippocampus. Extensive neurodegeneration occurred in the amygdaloid and hippocampal pyramidal cell regions in animals with marked IgGIR increase in these regions by 12 and 24 h after METH. A very rapid activation of brain microglia and/or infiltration of macrophages in regions of notable IgGIR increase with intense neurodegeneration were seen within 24 h. The phagocytosis rate of neurons in the hippocampus was so rapid that FJ-C labeling was virtually nonexistent 3 days after METH. METH did not produce IgGIR increase or neurodegeneration in the limbic regions in the absence of hyperthermia and seizures. Thus, high doses of METH can cause damage to the BBB when hyperthermia occurs, resulting in rapid and extensive hippocampal and amygdalar damage. The BBB disruption in the medial amygdala occurs first, and may well be contributing to the induction and severity of seizures, while BBB disruption in the hippocampus is likely a result of the seizures and hyperthermia. This hippocampal damage should be sufficient to compromise learning and memory. Published 2006 Wiley-Liss, lnc.