Background: High cholesterol has been correlated with a greater risk of cerebrovascular diseases. Whether pre-existing high cholesterol exacerbates traumatic brain injury (TBI), and whether treatment with the cholesterol-lowering agent simvastatin has neuroprotective effects, especially anti-neuroinflammatory effects, after TBI are not well investigated.
Methods: Five-week-old male Sprague-Dawley rats were fed a high-fat diet for 8 weeks to induce hypercholesterolemia. Anesthetized male Sprague-Dawley rats were divided into 5 groups, including the sham-operated control, TBI control, and TBI with simvastatin treatment (4 mg/kg, 10 mg/kg, or 20 mg/kg) groups. Simvastatin was intraperitoneally injected at 0, 24, and 48 hours after TBI. Motor function was measured using an inclined plane. Neuronal apoptosis (maker Neu-N, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling), tumor necrosis factor-α expression in microglia (marker OX42) and astrocytes (marker glial fibrillary acidic protein), and Tumor necrosis factor-alpha receptor (TNFR) 1 and TNFR2 expression in neurons in the ischemic cortex were investigated using an immunofluorescence assay. All of the parameters were measured on the third day after TBI.
Results: TBI significantly increased the serum levels of cholesterol. The TBI-induced motor deficit was significantly attenuated by 4, 10, and 20 mg/kg simvastatin therapy on the third day after TBI. TBI-induced neuronal TNFR1 activation and apoptosis, as well as tumor necrosis factor-α expression in astrocytes in the ischemic cortex, were significantly attenuated by simvastatin, particularly when 20 mg/kg was administered. Simultaneously, the serum cholesterol remained high despite simvastatin treatment.
Conclusions: The neuroprotection effects of simvastatin on the pre-existing hypercholesterolemia during TBI in rats may be related to its anti-neuroinflammatory effects but not to its cholesterol-lowing effects.
Keywords: Apoptosis, tumor necrosis factor-alpha; Cholesterol; Fluid percussion injury; Simvastatin; Tumor necrosis factor-alpha receptor.
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