The present study was designed to investigate the neuroprotective effect of ginseng total saponins (GTSs) and its underlying mechanisms in a rat model of traumatic brain injury (TBI). Rats were injected with GTSs (20 mg/kg, i.p.) or vehicle for 14 days after TBI. Neurological functions were determined using beam balance and prehensile traction tests at 1-14 days after trauma. Brain samples were extracted at 1 day after trauma for determination of water content, Nissl staining, enzyme-linked immunosorbent assay, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick end labeling, and measurement of oxidative stress variables and inflammatory cytokines. Moreover, the dose response of the neuroprotective effect and time window of the efficacy of GTSs were also determined. We found that treatment of GTSs 1) improved the neurological function with an effective dosage of 5-80 mg/kg and an efficacy time window of 3-6 hr after TBI; 2) reduced brain water content and neuronal loss in the hippocampal CA3 area; 3) increased the activity of superoxide dismutase and decreased the activity of nitric oxide synthase and the amount of malondialdehyde and nitric oxide; 4) down-regulated interleukin-1β, interleukin-6, and tumor necrosis factor-α and upregulated interleukin-10 in the cortical area surrounding the injured core; and 5) inhibited the apoptotic cell death and expression of caspase-3 and bax and raised the expression of bcl-2. These findings suggest that administration of GTSs after TBI could reduce the secondary injury through inhibiting oxidative and nitrative stress, attenuating inflammatory response, and reducing apoptotic cell death.
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