Abstract
Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid), arginine, and their combination on ischemic insults (cerebral edema and infarction) and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed 2 days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg), arginine (0.6 g/kg), or their combined administration (0.6 g/kg each). Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg), were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal) applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction), especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.
Highlights
Introduction lArginine, a basic amino acid, is a precursor of nitric oxide (NO) that displays potent vascular relaxant properties
Our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects
Suppression of glutamate-induced activity in the ventromedial nucleus of the hypothalamus (VMH) We investigated the effects of lysine and arginine on glutamateinduced VMH neuronal activity in awake rats
Summary
A basic amino acid, is a precursor of nitric oxide (NO) that displays potent vascular relaxant properties. Intravenous administration of arginine (Morikawa et al, 1992, 1994) or NO donors (Zhang and Iadecola, 1994) have been shown to reduce ischemic infarction, while administration of NO synthase (NOS) inhibitors exacerbates brain damage (Kuluz et al, 1993). It must be noted that different lines of evidence suggesting that arginine exacerbates (Zhao et al 2003) and NOS inhibitors ameliorate (Buisson et al, 1992; Kozniewska et al, 1995; Quast et al, 1995) ischemic infarction have been reported. Lysine is a potent inhibitor of arginase and blocks
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