Effects of tempol on white matter lesions and cognitive impairment in a rat model of chronic cerebral hypoperfusion

Abstract

To assess the neuroprotective effect of Tempol, an antioxidant acting as a superoxide dismutase mimic, on white matter lesions and cognitive impairment in rats with chronic cerebral hypoperfusion. Chronic cerebral ischemia was induced by permanent occlusion of bilateral common carotid arteries (2-VO) in male Wistar rats. The animals were divided into sham operation, saline-treated, Tempol (8 mg/kg) and Tempol (30 mg/kg) groups (n = 15 each). Performance of Morris water maze task and Western blot for myelin basic protein (MBP), amyloid precursor protein (APP) and 4-hydroxy-2-nonenal (HNE) modified proteins were analyzed at 6 weeks post-hypoperfusion. Tempol reduced the escape latency of Morris water maze post-hypoperfusion in comparison with the saline-treated rats (P < 0.05). The mean relative optical density of MBP in the white matter was significantly higher in Tempol (8 mg/kg) group (0.82 ± 0.17) and Tempol (30 mg/kg) group (0.91 ± 0.15) than saline-treated group (0.44 ± 0.13, all P < 0.01). The mean relative optical density of APP in white matter was significantly lower in Tempol (8 mg/kg) group (0.55 ± 0.13) and Tempol (30 mg/kg) group (0.46 ± 0.15) than saline-treated group (0.96 ± 0.19, all P < 0.01). The mean relative optical density of HNE-modified protein in white matter was significantly lower in Tempol (8 mg/kg) group (0.20 ± 0.035) and Tempol (30 mg/kg) group (0.18 ± 0.031) than saline-treated group (0.29 ± 0.039, all P < 0.01). Tempol ameliorates cognitive impairment by preventing white matter lesions induced by chronic cerebral hypoperfusion in rats. And it may protect white matter lesions in hypoperfused rats through reducing the formation of lipid peroxidation.