title: Hyperbaric oxygen preconditioning attenuates early apoptosis after spinal cord ischemia in rats.
abstract: This study tested the hypothesis that spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning (HBO-PC) is mediated by inhibition of early apoptosis. Male Sprague-Dawley rats were preconditioned with consecutive 4 cycles of 1-h HBO exposures (2.5 atmospheres absolute [ATA], 100% O(2)) at a 12-h interval. At 24 h after the last HBO pretreatment, rats underwent 9 min of spinal cord ischemia induced by occlusion of the descending thoracic aorta in combination with systemic hypotension (40 mmHg). Spinal cord ischemia produced marked neuronal death and neurological dysfunction in animals. HBO-PC enhanced activities of Mn-superoxide dismutase (Mn-SOD) and catalase, as well as the expression of Bcl-2 in the mitochondria in the normal spinal cord at 24 h after the last pretreatment (before spinal cord ischemia), and retained higher levels throughout the early reperfusion in the ischemic spinal cord. In parallel, superoxide and hydrogen peroxide levels in mitochondria were decreased, cytochrome c release into the cytosol was reduced at 1 h after reperfusion, and activation of caspase-3 and -9 was subsequently attenuated. HBO-PC improved neurobehavioral scores and reduced neuronal apoptosis in the anterior, intermediate, and dorsal gray matter of lumbar segment at 24 h after spinal cord ischemia. HBO-PC increased nitric oxide (NO) production. L-nitroarginine-methyl-ester (L-NAME; 10 mg/kg), a nonselective NO synthase (NOS) inhibitor, applied before each HBO-PC protocol abolished these beneficial effects of HBO-PC. We conclude that HBO-PC reduced spinal cord ischemia-reperfusion injury by increasing Mn-SOD, catalase, and Bcl-2, and by suppressing mitochondrial apoptosis pathway. NO may be involved in this neuroprotection.
authors.affiliation: Department of Anesthesiology, Changhai Hospital Affiliated to Second Military Medical University , Shanghai, PR China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Wenxian
authors.initials: W
authors.lastname: Li
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Kang
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Deng
authors.forename: Hengyi
authors.initials: H
authors.lastname: Tao
authors.forename: Weigang
authors.initials: W
authors.lastname: Xu
authors.forename: Runping
authors.initials: R
authors.lastname: Li
authors.forename: Xuejun
authors.initials: X
authors.lastname: Sun
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D006931:Hyperbaric Oxygenation / Q000379:methods*; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D028361:Mitochondrial Diseases / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D020760:Spinal Cord Ischemia / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D016896:Treatment Outcome