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Exp Neurol. 2010 Oct;225(2):391-401. doi: 10.1016/j.expneurol.2010.07.013. Epub 2010 Jul 27.

Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat.

Author information

1
Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.

Abstract

Sodium pyruvate (SP) treatment initiated within 5 min post-injury is neuroprotective in a rat model of unilateral cortical contusion injury (CCI). The current studies examined: (1) effects of delayed SP treatments (1000 mg/kg, i.p., at 1, 12 and 24h), (2) effects of single (1h) or multiple (1, 12 and 24h) ethyl pyruvate treatments (EP; at 20 or 40 mg/kg, i.p.), and (3) mechanisms of action for pyruvate effects after CCI. In Experiment 1, both SP and EP treatment(s) significantly reduced the number of dead/dying cells in the ipsilateral hippocampus (dentate hilus+CA3(c) and/or CA3(a-b) regions) at 72 h post-CCI. Pyruvate treatment(s) attenuated CCI-induced reductions of cerebral cytochrome oxidase activity at 7 2h, significantly improving activity in peri-contusional cortex after multiple SP or EP treatments. Optical density measures of ipsilateral CD11b immuno-staining were significantly increased 72 h post-CCI, but these measures of microglia activation were not different from sham injury values in SP and EP groups with three post-CCI treatments. In Experiment 2, three treatments (1, 12 and 24h) of SP (1000 mg/kg) or EP (40 mg/kg) significantly improved recovery of beam-walking and neurological scores in the first 3 weeks after CCI, and EP treatments significantly improved spatial working memory 1 week post-CCI. Ipsilateral CA3(b) neuronal loss, but not cortical tissue loss, was significantly reduced 1 month post-CCI with pyruvate treatments begun 1h post-CCI. Thus, delayed pyruvate treatments after CCI are neuroprotective and improve neurobehavioral recovery; these effects may be mediated by improved metabolism and reduced inflammation.

PMID:
20670624
PMCID:
PMC2939141
DOI:
10.1016/j.expneurol.2010.07.013
[Indexed for MEDLINE]
Free PMC Article

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