Objective      To investigate the effect of (S)-4C3HPG (S-4-carboxy-3-hydroxyphenylglycine) on acute brain injury at different time points after severe traumatic brain injury (sTBI) in mice

and to elucidate the possible mechanisms.       Methods       Mice model of sTBI was established by bumpiness of free falling body

and the model mice were injected with (S)-4C3HPG

5 mg/kg (i.p. n=10 per group)

at 15 min

1 h

3 h and 6 h after sTBI

respectively. Neurological deficit scores

water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF) were measured

and mRNA expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in injured cortex were detected by Real-time PCR at 24 h after TBI.       Results       Neurological deficits[(1.70±0.48) and (1.90±0.56)]

cerebral edema[(80.14±0.28)% and (80.17±0.52)%] and glutamate concentration in CSF[ (4.24±0.28) μmol/L and (6.12±0.23) μmol/L] were significantly attenuated or decreased in mice treated with (S)-4C3HPG at 15 min and 1 h post sTBI as compared with those in the control group[(2.80±0.42)

(82.55±0.34)% and (9.03±0.32) μmol/L; P0.01]. mRNA expressions of TNF-α[(0.722±0.160) and (0.793±0.122)] and IL-1β[(0.594±0.128) and (0.651±0.111)] significantly were decreased in mice treated with (S)-4C3HPG at 15 min and 1 h post sTBI as compared with those in the control group[(1.006±0.125) and (1.012±0.088); P0.01]. However

these changes were not significant in the groups of mice treated with (S)-4C3HPG at 3 h or 6 h post sTBI as compared with those of the control group.       Conclusion        (S)-4C3HPG treatment at early stage alleviates acute brain injury in sTBI

and its mechanism is possibly related to suppression of glutamate release.