Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment

Yimin Yuan, Zhida Su, Yingyan Pu, Xiujie Liu, Jingjing Chen, Feng Zhu, Yanling Zhu, Han Zhang, Cheng He

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background and Purpose: 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. Experimental Approach: 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. Key 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 -1day -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 -1day -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 and Implications: 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.

Original languageEnglish (US)
Pages (from-to)749-763
Number of pages15
JournalBritish Journal of Pharmacology
Volume166
Issue number2
DOIs
StatePublished - May 2012

Fingerprint

Spinal Cord Regeneration
Neuroglia
Spinal Cord Injuries
Regeneration
Spinal Cord
ethyl pyruvate
Neurons
Wounds and Injuries
Neuroprotective Agents
Axons

Keywords

  • astrogliosis
  • axon regeneration
  • ethyl pyruvate
  • glial scar
  • neuroinflammation
  • spinal cord injury

ASJC Scopus subject areas

  • Pharmacology

Cite this

Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment. / Yuan, Yimin; Su, Zhida; Pu, Yingyan; Liu, Xiujie; Chen, Jingjing; Zhu, Feng; Zhu, Yanling; Zhang, Han; He, Cheng.

In: British Journal of Pharmacology, Vol. 166, No. 2, 05.2012, p. 749-763.

Research output: Contribution to journalArticle

Yuan, Y, Su, Z, Pu, Y, Liu, X, Chen, J, Zhu, F, Zhu, Y, Zhang, H & He, C 2012, 'Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment', British Journal of Pharmacology, vol. 166, no. 2, pp. 749-763. https://doi.org/10.1111/j.1476-5381.2011.01804.x
Yuan, Yimin ; Su, Zhida ; Pu, Yingyan ; Liu, Xiujie ; Chen, Jingjing ; Zhu, Feng ; Zhu, Yanling ; Zhang, Han ; He, Cheng. / Ethyl pyruvate promotes spinal cord repair by ameliorating the glial microenvironment. In: British Journal of Pharmacology. 2012 ; Vol. 166, No. 2. pp. 749-763.
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AU - Yuan, Yimin

AU - Su, Zhida

AU - Pu, Yingyan

AU - Liu, Xiujie

AU - Chen, Jingjing

AU - Zhu, Feng

AU - Zhu, Yanling

AU - Zhang, Han

AU - He, Cheng

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AB - Background and Purpose: 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. Experimental Approach: 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. Key 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 -1day -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 -1day -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 and Implications: 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.

KW - astrogliosis

KW - axon regeneration

KW - ethyl pyruvate

KW - glial scar

KW - neuroinflammation

KW - spinal cord injury

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