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Glutamate metabolism of astrocytes during hyperbaric oxygen exposure and its effects on central nervous system oxygen toxicity

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Hyperbaric oxygen (HBO) has been used widely in many underwater missions and clinical work. However, exposure to extremely high oxygen pressure may cause central nervous system oxygen toxicity (CNS-OT). The regulation of astrocyte glutamate metabolism is closely related to epilepsy. This study aimed to observe the effects of HBO exposure on glutamate metabolism in astrocytes and confirm the role of glutamate metabolism in CNS-OT. Anesthetized rats were exposed to 5 atmosphere absolute HBO for 80 min and microdialysis samples of brain interstitial fluid were continuously collected. Extracellular glutamate and glutamine concentrations were also detected. Freely moving rats were exposed to HBO of the same pressure for 20 min and glutamine synthetase (GS) activity in brain tissues was measured. Finally, we observed the effects of different doses of drugs related to glutamate metabolism on the latency of CNS-OT. Results showed that HBO exposure significantly increased glutamate content, whereas glutamine content was significantly reduced. Moreover, HBO exposure significantly reduced GS activity. Glutamate transporter-1 (GLT-1) selective antagonist ceftriaxone prolonged CNS-OT latency, whereas GLT-1 selective inhibitor dihydrokainate shortened CNS-OT latency. In summary, HBO exposure improved glutamate concentration and reduced glutamine concentration by inhibition of GS activity. GLT-1 activation also participated in the prevention of HBO-induced CNS-OT. Our research will provide a potential new target to terminate or attenuate CNS-OT.
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Keywords: astrocytes; central nervous system oxygen toxicity; glutamate; glutamine; glutamine synthetase; hyperbaric oxygen

Document Type: Research Article

Affiliations: 1: Nautical and Aviation Medicine Center, Navy General Hospital of PLA, Beijing 2: Department of Pharmacy, Changhai Hospital 3: Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University 4: Tenth People’s Hospital of Tongji University, Shanghai, People’s Republic of China

Publication date: January 20, 2016

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