Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity.
Amphetamine- and methamphetamine-induced hyperthermia: Implications of the effects produced in brain vasculature and peripheral organs to forebrain neurotoxicity.
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DOI：
10.4161/23328940.2014.982049
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发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Hanig JP
中科院分区：
文献类型：
--
作者：
Bowyer JF;Hanig JP
本文讨论了苯丙胺（AMPH）和甲基苯丙胺（METH）引起的高温对血管、外周器官和外周免疫系统的不良影响。单独的高热不会产生安非他明样神经毒性，但不会产生高热（≥40°C）的AMPH和METH暴露具有极低的神经毒性。高温可能通过破坏蛋白质功能、离子通道和增强ROS产生直接增强AMPH和METH神经毒性。前脑神经毒性也可以通过AMPH和METH诱导的高温对血管系统的影响而间接影响。高剂量安非他明引起的体温过高和高血压是实验动物血脑屏障（BBB）短暂性破坏的主要原因，导致伴随的区域神经变性和神经炎症。这种BBB破坏可以发生在杏仁核、丘脑、纹状体、感觉和运动皮层以及海马体中。在这些条件下，反复发作大大增强了海马、丘脑和杏仁核的神经变性。即使血脑屏障受到较少的破坏，AMPH或METH诱导的对脑血管系统的高温效应也可能在神经毒性中发挥作用。在这种情况下，纹状体和皮质血管功能受到不利影响，并且在脑膜和皮质表面血管系统中观察到甚至更大的ROS、免疫和损伤反应。最后，当安非他明产生高热时，会导致肌肉和肝脏损伤以及血液中细胞因子升高。受损肌肉中的蛋白质可能会激活外周免疫系统并加剧肝脏损伤。肝损伤可以进一步增加细胞因子水平，免疫系统激活和增加氨水平。这些影响可能会增加血管损伤和神经毒性。
The adverse effects of amphetamine- (AMPH) and methamphetamine- (METH) induced hyperthermia on vasculature, peripheral organs and peripheral immune system are discussed. Hyperthermia alone does not produce amphetamine-like neurotoxicity but AMPH and METH exposures that do not produce hyperthermia (≥40°C) are minimally neurotoxic. Hyperthermia likely enhances AMPH and METH neurotoxicity directly through disruption of protein function, ion channels and enhanced ROS production. Forebrain neurotoxicity can also be indirectly influenced through the effects of AMPH- and METH- induced hyperthermia on vasculature. The hyperthermia and the hypertension produced by high doses amphetamines are a primary cause of transient breakdowns in the blood-brain barrier (BBB) resulting in concomitant regional neurodegeneration and neuroinflammation in laboratory animals. This BBB breakdown can occur in the amygdala, thalamus, striatum, sensory and motor cortex and hippocampus. Under these conditions, repetitive seizures greatly enhance neurodegeneration in hippocampus, thalamus and amygdala. Even when the BBB is less disrupted, AMPH- or METH- induced hyperthermia effects on brain vasculature may play a role in neurotoxicity. In this case, striatal and cortical vascular function are adversely affected, and even greater ROS, immune and damage responses are seen in the meninges and cortical surface vasculature. Finally, muscle and liver damage and elevated cytokines in blood can result when amphetamines produce hyperthermia. Proteins, from damaged muscle may activate the peripheral immune system and exacerbate liver damage. Liver damage can further increase cytokine levels, immune system activation and increase ammonia levels. These effects could potentially enhance vascular damage and neurotoxicity.