Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury.
Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n=6; CCI-Veh, n=7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n=7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (p<0.01) and from CCI-SP scores on days 4, 9 and 14 (p<0.05). Measures of cortical contusion volume, regional cerebral metabolic rates of glucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments.
Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California, Los Angeles, Los Angeles, CA 90095, USA. nmoro@mednet.ucla.edu
Nobuhiro
N
Moro
Sima S
SS
Ghavim
David A
DA
Hovda
Richard L
RL
Sutton
D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008570:Memory, Short-Term / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D019289:Pyruvic Acid / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018696:Neuroprotective Agents; D019289:Pyruvic Acid
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