Beneficial effects of sodium or ethyl pyruvate after traumatic brain injury in the rat.
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.
Moro
Nobuhiro
N
Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Sutton
Richard L
RL
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects*; D003576:Electron Transport Complex IV / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008568:Memory / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects; D011773:Pyruvates / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*
D011773:Pyruvates; D003576:Electron Transport Complex IV