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Methamphetamine METH is a powerful and often abused stimulant with potent addictive and neurotoxic properties. While it is generally assumed that multiple chemical substances released in the brain following METH-induced metabolic activation or oxidative stress are primary factors underlying damage of neural cells, in this work we will present data suggesting a role of brain hyperthermia and associated leakage of the brain-blood barrier BBB in acute METH-induced toxicity. First, we show that METH induces a dose-dependent brain and body hyperthermia, which is strongly potentiated by associated physiological activation and in warm environments that prevent proper heat dissipation to the external environment. Second, we demonstrate that acute METH intoxication induces robust, widespread but structure-specific leakage of the BBB, acute glial activation, and increased water content edema , which are related to drug-induced brain hyperthermia.
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