OBJECTIVE: Reactive oxygen species are thought to participate in the pathobiology of traumatic brain injury (TBI). This study determined whether treatment with LY341122, a potent inhibitor of lipid peroxidation and an antioxidant, would provide neuroprotection in a rat model of TBI. METHODS: To investigate the efficacy of LY341122 in this parasagittal fluid percussion model (1.8-2.1 atm), the rats received oral administration of LY341122 (100 mg/kg) or vehicle 2 hours before and 4 hours after TBI (each group, n = 7). To investigate the therapeutic window for treatment, rats were treated with LY341122 or vehicle for 20 hours by femoral vein infusion starting at 5 minutes, 30 minutes, or 3 hours after TBI (each group, n = 5). Three days after injury, analysis of contusion volumes and the frequency of damaged cortical neurons was conducted. RESULTS: Oral administration of LY341122 before and after TBI led to a significant reduction in overall contusion volume (3.28 mm3 ± 0.75 mm3 [mean ± standard error of the mean] versus 1.32 mm3 ± 0.33 mm3; P < 0.05) and also reduced the frequency of damaged cortical neurons (1191.7 ± 267.1 versus 474.6 ± 80.2; P < 0.05) in the second experiment, rats treated with LY341122 at 5 minutes or 30 minutes after TBI also demonstrated a significant reduction (P < 0.05) in contusion volume (1.92 mm3 ± 0.64 mm3 or 1.59 mm3 ± 0.50 mm3, respectively) compared with vehicle-treated rats (4.32 mm3 ± 1.15 mm3). A significant reduction in total cortical necrotic neuron counts was also demonstrated in the 5-minute group (2243.8 ± 265.3 versus 1457.8 ± 265.3; P < 0.05). In contrast, histopathological outcome was not significantly improved when treatment was delayed until 3 hours after TBI. CONCLUSION: These data reinforce the hypothesis that lipid peroxidation and reactive oxygen species participate in the acute pathogenesis of TBI. Treatment delayed until 3 hours after TBI did not provide significant histopathological protection.
- Fluid percussion brain injury
- Free radical scavenger
- Lipid peroxidation inhibitor
ASJC Scopus subject areas
- Clinical Neurology