In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry.

Abstract

Abuse of methamphetamine (METH) is a major and significant societal problem in the US, as a number of studies have suggested that METH is associated with increased cerebrovascular events, hemorrhage or vasospasm. Although cellular and molecular mechanisms involved in METH-induced toxicity are not completely understood, changes in brain O₂ may play an important role and contribute to METH-induced neurotoxicity including dopaminergic receptor degradation. Given that O₂ is the terminal electron acceptor for many enzymes that are important in brain function, the impact of METH on brain tissue pO₂ in vivo remains largely uncharacterized. This study investigated striatal tissue pO₂ changes in male C57BL/6 mice (16-20 g) following METH administration using EPR oximetry, a highly sensitive modality to measure pO₂ in vivo, in situ and in real time. We demonstrate that 20 min after a single injection of METH (8 mg/kg i.v.), the striatal pO₂ was reduced to 81% of the pretreatment level and exposure to METH for 3 consecutive days further attenuated striatal pO₂ to 64%. More importantly, pO₂ did not recover fully to control levels even 24 h after administration of a single dose of METH and continual exposure to METH exacerbates the condition. We also show a reduction in cerebral blood flow associated with a decreased brain pO₂ indicating an ischemic condition. Our findings suggests that administration of METH can attenuate brain tissue pO₂, which may lead to hypoxic insult, thus a risk factor for METH-induced brain injury and the development of stroke in young adults.

DOI: 10.1016/j.taap.2013.12.023
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@article{Weaver2014InVE, title={In vivo evidence of methamphetamine induced attenuation of brain tissue oxygenation as measured by EPR oximetry.}, author={John M Weaver and Yirong Yang and Rebecca S Purvis and Theodore Weatherwax and Gerald M . Rosen and Ke Liu}, journal={Toxicology and applied pharmacology}, year={2014}, volume={275 2}, pages={73-8} }