Early intravenous infusion of sodium nitrite protects brain against in vivo ischemia-reperfusion injury.
OBJECTIVE
The rate of nitric oxide (NO) generation from nitrite is linearly dependent on reductions in oxygen and pH levels. Recently, nitrite-derived NO has been reported to exert a profound protection against liver and heart ischemia-reperfusion injury. In this study, we hypothesized that nitrite would be reduced to NO in the ischemic brain and exert NO-dependent neuroprotective effects.


METHODS
Cerebral ischemia-reperfusion injury was induced by intraluminal thread occlusion of middle cerebral artery in the adult male rats. Solutions of sodium nitrite were infused intravenously at the time of reperfusion. Sodium nitrate and carboxy-PTIO (30 minutes before ischemic surgery), a direct NO scavenger, were infused for comparisons.


RESULTS
Nitrite reduced infarction volume and enhanced local cerebral blood flow and functional recovery. The effects were observed at concentrations of 48 nmol and 480 nmol, but not at 4800 nmol nitrite and 480 nmol nitrate. The neuroprotective effects of nitrite were inhibited completely by the carboxy-PTIO. The 480 nmol nitrite attenuated dihydroethidium activity, 3-nitrotyrosine formation, and lipid peroxidation in the ischemic brain.


CONCLUSIONS
Nitrite exerted profound neuroprotective effects with antioxidant properties in the ischemic brains. These results suggest that nitrite, as a biological storage reserve of NO, may be a novel therapeutic agent in the setting of acute stroke.
Jung
Keun-Hwa
KH
Stroke & Neural Stem Cell Laboratory in the Clinical Research Inst, Stem Cell Research Center, Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
Chu
Kon
K
Ko
Song-Yi
SY
Lee
Soon-Tae
ST
Sinn
Dong-In
DI
Park
Dong-Kyu
DK
Kim
Jeong-Min
JM
Song
Eun-Cheol
EC
Kim
Manho
M
Roh
Jae-Kyu
JK
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D007262:Infusions, Intravenous; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D012977:Sodium Nitrite / Q000008:administration & dosage*; D013997:Time Factors
D018696:Neuroprotective Agents; D012977:Sodium Nitrite