title: Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment.
abstract: OBJECTIVE
  Spinal cord injury (SCI) triggers a series of endogenous processes, including neuroinflammation and reactive astrogliosis, which may contribute to the failure of neural regeneration and functional recovery. In the present study, the effect of ethyl pyruvate on spinal cord repair was explored.
  
  
  METHODS
  Functional assessment and histological analyses of astrogliosis, neuroinflammation, neuronal survival and axonal regeneration were performed to investigate the effects of ethyl pyruvate (0.086, 0.215, 0.431 or 0.646 mmol·kg(-1) ·day(-1) ) on spinal cord repair in a rat model of SCI. The effect of ethyl pyruvate (5, 10 or 15 mM) on astrocytic activation was also evaluated in an in vitro'scratch-wound' model.
  
  
  RESULTS
  Functional assessment showed evident improvement of behavioural functions in the ethyl pyruvate-treated rats. Reactive astrogliosis was significantly inhibited in vivo, after injection of ethyl pyruvate (0.431 mmol·kg(-1) day(-1) ), and in vitro'scratch-wound' model in the presence of 10 or 15 mM ethyl pyruvate. The difference between effective concentration in vitro and in vivo suggests that the inhibitory effect of ethyl pyruvate on astrogliosis in damaged spinal cord is indirect. In addition, ethyl pyruvate (0.431 mmol·kg(-1) day(-1) ) attenuated SCI-induced neuroinflammation; it decreased the Iba-1-, ED-1- and CD11b-positive cells at the lesion site. Importantly, histological analyses showed a significantly greater number of surviving neurons and regenerative axons in the ethyl pyruvate-treated rats.
  
  
  CONCLUSIONS
  Ethyl pyruvate was shown to inhibit astrogliosis and neuroinflammation, promote neuron survival and neural regeneration, and improve the functional recovery of spinal cord, indicating a potential neuroprotective effect of ethyl pyruvate against SCI.
authors.affiliation: Institute of Neuroscience and MOE Key Laboratory of Molecular Neurobiology, Neuroscience Research Center of Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yuan
authors.forename: Zhida
authors.initials: Z
authors.lastname: Su
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Pu
authors.forename: Xiujie
authors.initials: X
authors.lastname: Liu
authors.forename: Jingjing
authors.initials: J
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Yanling
authors.initials: Y
authors.lastname: Zhu
authors.forename: Han
authors.initials: H
authors.lastname: Zhang
authors.forename: Cheng
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001522:Behavior, Animal / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011773:Pyruvates / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology
chemical_list: D018696:Neuroprotective Agents; D011773:Pyruvates; C046522:ethyl pyruvate