Brain edema and breakdown of the blood-brain barrier during methamphetamine intoxication: critical role of brain hyperthermia.

摘要: To clarify the role of brain temperature in permeability blood–brain barrier (BBB), rats were injected with methamphetamine (METH 9 mg/kg) at normal (23 °C) and warm (29 °C) environmental conditions internal temperatures monitored both centrally (nucleus accumbens, NAcc) peripherally (skin nonlocomotor muscle). Once NAcc peaked or reached 41.5 °C (a level suggesting possible lethality), animals administered Evans blue dye (protein tracer that does not normally cross BBB), rapidly anaesthetized, perfused had their brains removed. All METH-treated showed body hyperthermia associated relative skin hypothermia, metabolic activation coupled peripheral vasoconstriction. While METH-induced elevation varied from 37.60 to 42.46 °C (or 1.2–5.1 °C above baseline), it was stronger 29 °C (+4.13 °C) than 23 °C (+2.31 °C). Relative control, significantly higher levels water, Na+, K+ Cl–, edema, intense immunostaining for albumin, indicating breakdown BBB. also strong immunoreactivity glial fibrillary acidic protein (GFAP), possibly acute abnormality damage astrocytes. changes albumin GFAP correlated linearly (r = 0.93, 0.98 0.98, respectively), a key BBB permeability, development edema subsequent functional structural neural abnormalities. Therefore, along direct destructive action on cells functions, hyperthermia, via BBB, may be crucial decompensation functions cell injury following METH intoxication, contributing neurodegeneration resulting chronic drug use.