• Zeqi Zhong, Yuan Tao, and Hui Yang.
• Department of Neurosurgery, Xinqiao Hospital, The Third Military Medical University, Chongqing 400037, P.R. China.
• Mol Med Rep. 2015 Dec 1; 12 (6): 7985-91.

AbstractTraumatic brain injury (TBI) is a leading cause of mortality in young individuals, and results in motor and cognitive deficiency. Excitotoxicity is an important process during neuronal cell death, which is caused by excessive release of glutamate following TBI. Astrocytic glutamate transporters have a predominant role in maintaining extracellular glutamate concentrations below excitotoxic levels, and glutamate transporter 1 (GLT‑1) may account for >90% of glutamate uptake in the brain. The β‑carboline alkaloid harmine has been demonstrated to exert neuroprotective actions in vivo, and the beneficial effects were specifically due to elevation of GLT‑1. However, whether harmine provides neuroprotection following TBI remains to be elucidated. The present study performed intraperitoneal harmine injections in rats (30 mg/kg per day for up to 5 days), in order to investigate whether harmine treatment attenuates brain edema and improves functional recovery in a rat model of TBI. The neuronal survival ratio and the protein expression of apoptosis‑associated caspase 3 were also assessed in the hippocampus of the rat brain. Furthermore, the expression levels of GLT‑1 and inflammatory cytokines were detected, in order to determine the underlying mechanisms. The results of the present study demonstrated that administration of harmine significantly attenuated cerebral edema, and improved learning and memory ability. In addition, harmine significantly increased the protein expression of GLT‑1, and markedly attenuated the expression levels of interleukin‑1β and tumor necrosis factor‑α, thereby attenuating apoptotic neuronal death in the hippocampus. These results provided in vivo evidence that harmine may exert neuroprotective effects by synergistically reducing excitotoxicity and inflammation following TBI.

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