title: Effects of adenosine metabolism in astrocytes on central nervous system oxygen toxicity.
abstract: Hyperbaric oxygen (HBO) is widely used in military operations, especially underwater missions. However, prolonged and continuous inhalation of HBO can cause central nervous system oxygen toxicity (CNS-OT), which greatly limits HBO's application. The regulation of astrocytes to the metabolism of adenosine is involved in epilepsy. In our study, we aimed to observe the effects of HBO exposure on the metabolism of adenosine in the brain. Furthermore, we aimed to confirm the possible mechanism underlying adenosine's mediation of the CNS-OT. Firstly, anesthetized rats exposed to 5 atm absolute HBO for 80 min. The concentrations of extracellular adenosine, ATP, ADP, and AMP were detected. Secondly, free-moving rats were exposed to HBO at the same pressure for 20 min, and the activities of 5'-nucleotidase and ADK in brain tissues were measured. For the mechanism studies, we observed the effects of a series of different doses of drugs related to adenosine metabolism on the latency of CNS-OT. Results showed HBO exposure could increase adenosine content by inhibiting ADK activity and improving 5'-nucleotidase activity. And adenosine metabolism during HBO exposure may be a protective response against HBO-induced CNS-OT. Moreover, the improvement of adenosine concentration, activation of adenosine A1R, or suppression of ADK and adenosine A2AR, which are involved in the prevention of HBO-induced CNS-OT. This is the first study to demonstrate HBO exposure regulated adenosine metabolism in the brain. Adenosine metabolism and adenosine receptors are related to HBO-induced CNS-OT development. These results will provide new potential targets for the termination or the attenuation of CNS-OT.
authors.affiliation: Nautical and Aviation Medicine Center, Navy General Hospital of PLA, Beijing 100048, China.
authors.forename: Yu-liang
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhong-zhuang
authors.initials: ZZ
authors.lastname: Wang
authors.affiliation: Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China.
authors.forename: Wei-gang
authors.initials: WG
authors.lastname: Xu
authors.affiliation: Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433, China. Electronic address: smartrpli@hotmail.com.
authors.forename: Run-ping
authors.initials: RP
authors.lastname: Li
authors.affiliation: Tenth People׳s Hospital of Tongji University, Shanghai 200072, China. Electronic address: zhangjd534@163.com.
authors.forename: Jun-dong
authors.initials: JD
authors.lastname: Zhang
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D000241:Adenosine / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008297:Male; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015720:5'-Nucleotidase; D000241:Adenosine; D010100:Oxygen
keywords: Adenosine; Adenosine receptor; Astrocytes; Central nervous system oxygen toxicity; Hyperbaric oxygen