Repetitive hyperbaric oxygen exposures enhance sensitivity to convulsion by upregulation of eNOS and nNOS.
BACKGROUND
Repetitive hyperbaric oxygen (HBO) exposures as preconditioning methods produce ischemic tolerance, but may increase the risk of convulsions in patients. The purpose of this study was to investigate the mechanisms in increased sensitivity to convulsions and the role of nitric oxide (NO) and its synthases after repetitive HBO exposures.


METHODS
Mice were randomly assigned into three groups: HBO group, hyperbaric air (HBA) group and normobaric air (NBA) group. Mice in HBO or HBA group were exposed to hyperbaric oxygen or hyperbaric air respectively for 60 min twice daily for 3 consecutive days (2.5 atmosphere absolute [ATA]). 24 h after the last exposure, mice were exposed to HBO (100% O2, 6 ATA). The latency of convulsions was recorded. In addition, the levels of NO, NADPH-diaphorase, mRNA and protein expressions of NOS isoforms in hypothalamus and hippocampus were determined.


RESULTS
Latency to seizures was significantly shortened in mice after six HBO pre-exposures. The level of NO in hypothalamus in HBO group was increased. The number of NADPH-d positive cells and the levels of protein and mRNA of eNOS and nNOS in hypothalamus and hippocampus were increased.


CONCLUSIONS
After repeated HBO exposures, elevated NO may enhance the sensitivity to convulsions and this may lead to seizures during the subsequent oxygen exposures. Prevention of seizures is needed when HBO is used as preconditioning method.
Liu
Wenwu
W
Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, and Department of Neurology, Changhai Hospital, Shanghai, 200433, PR China.
Li
Jiasi
J
Sun
Xuejun
X
Liu
Kan
K
Zhang
John H
JH
Xu
Weigang
W
Tao
Hengyi
H
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D001923:Brain Chemistry / Q000502:physiology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000201:enzymology; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D007031:Hypothalamus / Q000201:enzymology; D008297:Male; D051379:Mice; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000009:adverse effects; D012333:RNA, Messenger / Q000378:metabolism; D012640:Seizures / Q000201:enzymology* / Q000209:etiology* / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D012333:RNA, Messenger; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; D009252:NADPH Dehydrogenase; D010100:Oxygen