• Hong Shi, Hai-Lian Wang, Hong-Jian Pu, Ye-Jie Shi, Jia Zhang, Wen-Ting Zhang, Guo-Hua Wang, Xiao-Ming Hu, Rehana K Leak, Jun Chen, and Yan-Qin Gao.
• Department of Anesthesiology of Huashan Hospital, State Key Laboratory of Medical Neurobiology and Institute of Brain Sciences, Fudan University, Shanghai, China; Department of Anesthesiology of Shanghai Pulmonary Hospital, Tongji University, Shanghai, China.
• CNS Neurosci Ther. 2015 Apr 1; 21 (4): 374-84.

AimsMany traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms.MethodsMale adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity, and neuroinflammation were assessed.ResultsEthyl pyruvate improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 day post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent antiinflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI.ConclusionEthyl pyruvate confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation, and long-lasting brain damage.© 2014 John Wiley & Sons Ltd.

46 keywords...

hide…