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[Effect of (S)-4C3HPG on brain damage in the acute stage of moderate traumatic brain injury model of mice and underlying mechanism.] [Ariticle in Chinese]

Yang Nan, DAI Shuang-Shuang, NING Ya-Lei, CHEN Xing-Yun, ZHAO Yan, LI Ping, ZHOU Yuan-Guo

Molecular Biology Center, State Key Laboratory of Trauma, Burn and Combined Injury, Research Institute of Surgery and Daping Hospital, Third Military Medical University, Chongqing 400042, China； Department of Biochemistry and Molecular Biology, Third Military Medical University, Chongqing 400038, China

Abstract

The aim of this study is to investigate the effect of (S)-4-carboxy-3-hydroxy-phenylglycine [(S)-4C3HPG], a mixed group I glutamate metabotropic receptor antagonist and a group II agonist, on impairment in a cortical impact model of traumatic brain injury (TBI) in mice and to elucidate the possible mechanisms. Mice were injected (i.p.) with saline, 1 mg/kg (S)-4C3HPG, 5 mg/kg (S)- 4C3HPG and 10 mg/kg (S)-4C3HPG (n=10 per group), respectively, at 30 min before moderate TBI. Neurological deficit scores, water content in injured brain and glutamate concentration in cerebral spinal fluid (CSF) were detected at 24 h after TBI. The expressions of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) mRNA in injured cortex were also detected by real-time RT-PCR. The results showed that the neurological deficits and cerebral edema were significantly attenuated in mice pretreated with (S)-4C3HPG (5 and 10 mg/kg respectively) compared with those in mice pretreated with saline. Furthermore, (S)-4C3HPG treatment also decreased the glutamate concentration in CSF and the expressions of TNF-α and IL-1β mRNA remarkably in a dose-dependent manner. These results suggest that (S)-4C3HPG treatment attenuates cortical impact-induced brain injury possibly via suppression of glutamate release and inhibition of excessive inflammatory cytokine production. These findings highlight the potential benefit of glutamate metabotropic receptor ligand for preventing TBI.

Key words: metabotropic glutamate receptor; craniocerebral trauma; inflammation; glutamate

Received: 2010-08-17　　Accepted: 2010-10-11

Corresponding author: 周元国　　E-mail: ygzhou@cta.cq.cn

Citing This Article：

Yang Nan, DAI Shuang-Shuang, NING Ya-Lei, CHEN Xing-Yun, ZHAO Yan, LI Ping, ZHOU Yuan-Guo. [Effect of (S)-4C3HPG on brain damage in the acute stage of moderate traumatic brain injury model of mice and underlying mechanism.] [Ariticle in Chinese] . Acta Physiol Sin 2010; 62 (6): 555-559 (in Chinese with English abstract).