Effect of ascorbic acid, dihydrolipoic acid, t‐Butylhydroquinone, and phenylbutylnitrone on mortality and neurological impairment induced by sequential common carotid artery sectioning in mice

Abstract

AbstractThe efficacy of four antioxidant agents to reduce neurological deficits and mortality produced by sequential common carotid artery sectioning (SCAS) in mice was evaluated. Ascorbic acid (AA, 500 mg/kg), dihydrolipoic acid (DHLA, 100 mg/kg), tert‐butylhydroquinone (t‐BHQ, 100 mg/kg) or phenylbutylnitrone (PBN, 100 mg/kg) were injected ip 15 min after the second artery sectioning. Animals were evaluated at 24, 48, and 72 h after antioxidant or saline injection using two procedures: neurological examination and spontaneous motility. Based on neurological examination, a disability status scale was used to determine the degree of functional incapacity after brain ischemia for each animal. The scale comprised 10 progressive steps beyond 0 (normal) extending to status 10 (death due to SCAS). In this scale, the highest scores reflect greater neurological dysfunction. AA and DHLA but neither t‐BHQ nor PBN decreased mortality and reduced neurobehavioral deficits caused by SCAS in mice. The observed 24‐, 48‐, and 72‐h survival rates for AA were 86, 71, and 48% and for DHLA were 75, 65, and 65%, representing a significant prolongation of lifespan as compared with vehicle‐treated animals (60, 35, 35%). The 24‐, 48‐, and 72‐h neurological scores for AA of 5.2, 6.2, and 7.5 and for DHLA of 4.6, 5.3, and 5.8 as compared with the scores observed for the saline‐treated control group (7.6, 8.6, and 8.6) indicate that administration of these antioxidants is beneficial for the neurological output of surviving animals. These antioxidants may have important neuroprotective properties, and indicate that a clinical trial, mainly of DHLA, in stroke patients should be considered. Drug Dev. Res. 63:212–218, 2004. © 2004 Wiley‐Liss, Inc.