title: Mild hypoxemia during initial reperfusion alleviates the severity of secondary energy failure and protects brain in neonatal mice with hypoxic-ischemic injury.
abstract: Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates oxidative brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the reperfusion was initiated by reoxygenation with room air (RA) followed by the exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic oxygen saturation (SaO(2)), cerebral blood flow (CBF), brain mitochondrial respiration and permeability transition pore (mPTP) opening, markers of oxidative injury, and cerebral infarcts were assessed. Compared with RA-littermates, HI-mice exposed to 18% oxygen exhibited significantly decreased infarct volume, oxidative injury in the brain mitochondria and tissue. This was coupled with improved mitochondrial tolerance to mPTP opening. Oxygen saturation maintained during reperfusion at 85% to 95% was associated (r=0.57) with the best neurologic outcome. Exposure to 100% or 15% oxygen significantly exacerbated brain injury and oxidative stress. Compared with RA-mice, hyperoxia dramatically increased reperfusion CBF, but exposure to 15% oxygen significantly reduced CBF to values observed during the HI-insult. Mild hypoxemia during initial reperfusion alleviates the severity of HI-brain injury by limiting the reperfusion-driven oxidative stress to the mitochondria and mPTP opening. This suggests that at the initial stage of reperfusion, a slightly decreased systemic oxygenation (SaO(2) 85% to 95%) may be beneficial for infants with birth asphyxia.
authors: Department of Pediatrics, Columbia University, New York, New York 10032, USA.
authors: Zoya V
authors: ZV
authors: Niatsetskaya
authors: Pradeep
authors: P
authors: Charlagorla
authors: Dzmitry A
authors: DA
authors: Matsukevich
authors: Sergey A
authors: SA
authors: Sosunov
authors: Korapat
authors: K
authors: Mayurasakorn
authors: Veniamin I
authors: VI
authors: Ratner
authors: Richard A
authors: RA
authors: Polin
authors: Anatoly A
authors: AA
authors: Starkov
authors: Vadim S
authors: VS
authors: Ten
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D015424:Reperfusion / Q000379:methods
chemical_list: D010100:Oxygen; D002118:Calcium