Abstract
ABSTRACT: 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.
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Ashwal, S., Cole, D., Osborne, S. et al. L-NAME Reduces Infarct Volume in a Filament Model of Transient Middle Cerebral Artery Occlusion in the Rat Pup. Pediatr Res 38, 652–656 (1995). https://doi.org/10.1203/00006450-199511000-00004
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DOI: https://doi.org/10.1203/00006450-199511000-00004
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