title: Dietary supplementation with sodium nitrite can exert neuroprotective effects on global cerebral ischemia/reperfusion in mice.
abstract: BACKGROUND
  Nitrite-derived NO protects against middle cerebral artery occlusion in mice. We developed a new mouse model of global cerebral ischemia and reperfusion (GCI/R) involving reversible occlusion of the major vessels from the aortic arch supplying the brain, and investigated neuroprotection with dietary sodium nitrite supplementation against GCI/R injury.
  
  
  METHODS
  Mice received drinking water with (nitrite group) or without (control group) sodium nitrite (2 mM) for 5 days and underwent 3-min GCI/R by reversible occlusion of major vessels from the aortic arch (i.e., brachiocephalic, left common carotid, and left subclavian artery). Survival rates and neurological function scores were evaluated for up to 5 days after GCI/R. Histopathological studies were performed to detect neurological degeneration and caspase-3 activation in serial hippocampal sections.
  
  
  RESULTS
  In the control group, 17/30 mice (57 %) survived 5 days after 3-min GCI/R, whereas in the nitrite group 25/30 mice (83 %) survived (p < 0.05). The neurological score at 5 days after GCI in control group was significantly higher than in the nitrite group. Cerebral blood flow (CBF) during GCI was significantly higher in the nitrite group than in the control group, while MABP did not differ significantly between groups. Degenerative changes and caspase-3 activation in hippocampal sections after GCI were observed in the control group but not in the nitrite group. Pretreatment with the NO scavenger c-PTIO abolished the neuroprotective effects of sodium nitrite.
  
  
  CONCLUSIONS
  Sodium nitrite supplementation attenuated mortality and neurological impairment after 3-min GCI in mice; an effect likely mediated via vascular mechanisms involving NO.
authors.affiliation: Department of Anesthesiology, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa, 903-0215, Japan, takasuke0302@gmail.com.
authors.forename: Takasuke
authors.initials: T
authors.lastname: Fukuda
authors.forename: Manabu
authors.initials: M
authors.lastname: Kakinohana
authors.forename: Chitoshi
authors.initials: C
authors.lastname: Takayama
authors.forename: Masayuki
authors.initials: M
authors.lastname: Matsushita
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Sugahara
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects; D019587:Dietary Supplements; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D015427:Reperfusion Injury / Q000188:drug therapy*; D012977:Sodium Nitrite / Q000494:pharmacology*
chemical_list: D018696:Neuroprotective Agents; D053148:Caspase 3; D012977:Sodium Nitrite