Ethyl Pyruvate Protects against Blood–Brain Barrier Damage and Improves Long‐term Neurological Outcomes in a Rat Model of Traumatic Brain Injury. (23rd December 2014)

• Record Type: Journal Article
• Authors: Shi, Hong; Wang, Hai‐Lian; Pu, Hong‐Jian; Shi, Ye‐Jie; Zhang, Jia; Zhang, Wen‐Ting; Wang, Guo‐Hua; Hu, Xiao‐Ming; Leak, Rehana K.; Chen, Jun; Gao, Yan‐Qin
• Is Part Of: CNS neuroscience & therapeutics. Volume 21:Number 4(2015)
• Page Start: 374
• Page End: 384
• Publication Date: 2014-12-23
• Subjects: Blood–brain barrier -- Ethyl pyruvate -- Inflammation -- Neuroprotection -- Traumatic brain injury; Neuropharmacology -- Periodicals; Central nervous system -- Diseases -- Effect of drugs on -- Periodicals; 612.8
• DOI: 10.1111/cns.12366
• Languages: English
• ISSNs: 1755-5930

Abstract

Summary: Aims: Many 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. Methods: Male 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. Results: Ethyl 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. Conclusion: Ethyl 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.