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.
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: Petra Kleinbongard; André Dejam; Thomas Lauer; Thomas Jax; Stefan Kerber; Putrika Gharini; Jan Balzer; Rainer B Zotz; Rüdiger E Scharf; Reinhart Willers; Alan N Schechter; Martin Feelisch; Malte Kelm Journal: Free Radic Biol Med Date: 2005-11-10 Impact factor: 7.376
Authors: Mark R Duranski; James J M Greer; Andre Dejam; Sathya Jaganmohan; Neil Hogg; William Langston; Rakesh P Patel; Shaw-Fang Yet; Xunde Wang; Christopher G Kevil; Mark T Gladwin; David J Lefer Journal: J Clin Invest Date: 2005-04-14 Impact factor: 14.808
Authors: Kenyatta Cosby; Kristine S Partovi; Jack H Crawford; Rakesh P Patel; Christopher D Reiter; Sabrina Martyr; Benjamin K Yang; Myron A Waclawiw; Gloria Zalos; Xiuli Xu; Kris T Huang; Howard Shields; Daniel B Kim-Shapiro; Alan N Schechter; Richard O Cannon; Mark T Gladwin Journal: Nat Med Date: 2003-11-02 Impact factor: 53.440
Authors: Andrew Webb; Richard Bond; Peter McLean; Rakesh Uppal; Nigel Benjamin; Amrita Ahluwalia Journal: Proc Natl Acad Sci U S A Date: 2004-09-03 Impact factor: 11.205
Authors: Petra Kleinbongard; André Dejam; Thomas Lauer; Tienush Rassaf; Achim Schindler; Olaf Picker; Thomas Scheeren; Axel Gödecke; Jürgen Schrader; Rainer Schulz; Gerd Heusch; Günter A Schaub; Nathan S Bryan; Martin Feelisch; Malte Kelm Journal: Free Radic Biol Med Date: 2003-10-01 Impact factor: 7.376