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L-NAME reduces infarct volume in a filament model of transient middle cerebral artery occlusion in the rat pup. 1995

S Ashwal, and D J Cole, and S Osborne, and T N Osborne, and W J Pearce
Department of Pediatrics, Loma Linda University School of Medicine, California 92354, USA.

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.

UI MeSH Term Description Entries
D009569 Nitric Oxide A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP. Endogenous Nitrate Vasodilator,Mononitrogen Monoxide,Nitric Oxide, Endothelium-Derived,Nitrogen Monoxide,Endothelium-Derived Nitric Oxide,Monoxide, Mononitrogen,Monoxide, Nitrogen,Nitrate Vasodilator, Endogenous,Nitric Oxide, Endothelium Derived,Oxide, Nitric,Vasodilator, Endogenous Nitrate
D009757 Nylons Polymers where the main polymer chain comprises recurring amide groups. These compounds are generally formed from combinations of diamines, diacids, and amino acids and yield fibers, sheeting, or extruded forms used in textiles, gels, filters, sutures, contact lenses, and other biomaterials. Polyamides,Dermalon,Ethilon,Nylon,Polyamide,Supramid,Dermalons,Ethilons,Supramids
D011918 Rats, Inbred SHR A strain of Rattus norvegicus with elevated blood pressure used as a model for studying hypertension and stroke. Rats, Spontaneously Hypertensive,Rats, SHR,Inbred SHR Rat,Inbred SHR Rats,Rat, Inbred SHR,Rat, SHR,Rat, Spontaneously Hypertensive,SHR Rat,SHR Rat, Inbred,SHR Rats,SHR Rats, Inbred,Spontaneously Hypertensive Rat,Spontaneously Hypertensive Rats
D002536 Cerebral Arteries The arterial blood vessels supplying the CEREBRUM. Arteries, Cerebral,Artery, Cerebral,Cerebral Artery
D002544 Cerebral Infarction The formation of an area of NECROSIS in the CEREBRUM caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., INFARCTION, ANTERIOR CEREBRAL ARTERY), and etiology (e.g., embolic infarction). Anterior Choroidal Artery Infarction,Cerebral Infarct,Infarction, Cerebral,Posterior Choroidal Artery Infarction,Subcortical Infarction,Cerebral Infarction, Left Hemisphere,Cerebral Infarction, Right Hemisphere,Cerebral, Left Hemisphere, Infarction,Cerebral, Right Hemisphere, Infarction,Infarction, Cerebral, Left Hemisphere,Infarction, Cerebral, Right Hemisphere,Infarction, Left Hemisphere, Cerebral,Infarction, Right Hemisphere, Cerebral,Left Hemisphere, Cerebral Infarction,Left Hemisphere, Infarction, Cerebral,Right Hemisphere, Cerebral Infarction,Right Hemisphere, Infarction, Cerebral,Cerebral Infarctions,Cerebral Infarcts,Infarct, Cerebral,Infarction, Subcortical,Infarctions, Cerebral,Infarctions, Subcortical,Infarcts, Cerebral,Subcortical Infarctions
D002546 Ischemic Attack, Transient Brief reversible episodes of focal, nonconvulsive ischemic dysfunction of the brain having a duration of less than 24 hours, and usually less than one hour, caused by transient thrombotic or embolic blood vessel occlusion or stenosis. Events may be classified by arterial distribution, temporal pattern, or etiology (e.g., embolic vs. thrombotic). (From Adams et al., Principles of Neurology, 6th ed, pp814-6) Brain Stem Ischemia, Transient,Cerebral Ischemia, Transient,Crescendo Transient Ischemic Attacks,Transient Ischemic Attack,Anterior Circulation Transient Ischemic Attack,Brain Stem Transient Ischemic Attack,Brain TIA,Brainstem Ischemia, Transient,Brainstem Transient Ischemic Attack,Carotid Circulation Transient Ischemic Attack,Posterior Circulation Transient Ischemic Attack,TIA (Transient Ischemic Attack),Transient Ischemic Attack, Anterior Circulation,Transient Ischemic Attack, Brain Stem,Transient Ischemic Attack, Brainstem,Transient Ischemic Attack, Carotid Circulation,Transient Ischemic Attack, Posterior Circulation,Transient Ischemic Attack, Vertebrobasilar Circulation,Transient Ischemic Attacks, Crescendo,Vertebrobasilar Circulation Transient Ischemic Attack,Attack, Transient Ischemic,Attacks, Transient Ischemic,Brainstem Ischemias, Transient,Cerebral Ischemias, Transient,Ischemia, Transient Brainstem,Ischemia, Transient Cerebral,Ischemias, Transient Brainstem,Ischemias, Transient Cerebral,Ischemic Attacks, Transient,TIA, Brain,TIAs (Transient Ischemic Attack),Transient Brainstem Ischemia,Transient Cerebral Ischemia,Transient Cerebral Ischemias,Transient Ischemic Attacks
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001120 Arginine An essential amino acid that is physiologically active in the L-form. Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D001157 Arterial Occlusive Diseases Pathological processes which result in the partial or complete obstruction of ARTERIES. They are characterized by greatly reduced or absence of blood flow through these vessels. They are also known as arterial insufficiency. Arterial Obstructive Diseases,Arterial Occlusion,Arterial Obstructive Disease,Arterial Occlusions,Arterial Occlusive Disease,Disease, Arterial Obstructive,Disease, Arterial Occlusive,Obstructive Disease, Arterial,Occlusion, Arterial,Occlusive Disease, Arterial

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