L-NAME reduces infarct volume in a filament model of transient middle cerebral artery occlusion in the rat pup.
The importance of nitric oxide (NO) during focal cerebral ischemia remains controversial as studies have suggested both a neurotoxic and neuroprotective role. In the 7 d old rat pup, NG-nitro-L-arginine, a nitric oxide synthase inhibitor, reduced infarct volume in a model of unilateral carotid ligation with 2.5 h exposure to 8% O2. The current study examined whether NO is neurotoxic in a filament model of transient middle cerebral artery occlusion (MCAO) in the 14-18-d-old rat pup. We developed a reproducible filament model of transient MCAO in 14-18-d-old spontaneously hypertensive rats (35 g) by passing a no. 6-0 (0.07-mm) nylon filament via the carotid artery to occlude the middle cerebral artery for 4 h under normoxic conditions. After filament removal and reperfusion for 24 h, we determined infarct volume using the mitochondrial stain 2,3,5-triphenyltetrazolium chloride. NO synthesis was inhibited using NG-nitro-L-arginine methyl ester (L-NAME) at a dose of 3 mg/kg, intraperitoneally, 1 h before MCAO. We measured infarct volume in control (n = 7) and L-NAME (n = 7) groups. L-NAME reduced infarct volume by 55% (p < 0.01). In the control group, infarct volume (180 +/- 29 mm3) averaged 49 +/- 7% of the left hemisphere (359 +/- 16 mm3). In the L-NAME-treated group, infarct volume (77 +/- 19 mm3) was 22 +/- 5% of the left hemispheric volume (344 +/- 2 mm3). These findings support earlier studies that used models of neonatal hypoxic-ischemic brain injury and suggest a neurotoxic role of NO. They extend these observations by demonstrating a significant reduction in infarct volume in a stroke model in the immature rat pup.
Ashwal
S
S
Department of Pediatrics, Loma Linda University School of Medicine, California 92354, USA.
Cole
D J
DJ
Osborne
S
S
Osborne
T N
TN
Pearce
W J
WJ
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001157:Arterial Occlusive Diseases / Q000378:metabolism*; D002536:Cerebral Arteries; D002544:Cerebral Infarction / Q000378:metabolism*; D004195:Disease Models, Animal; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009757:Nylons; D051381:Rats; D011918:Rats, Inbred SHR
D009757:Nylons; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester