Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury

Abstract

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.

Pyruvate prevents the development of age-dependent cognitive deficits in a mouse model of Alzheimer's disease without reducing amyloid and tau pathology

“…Previous studies in rats subjected to insulin-induced hypoglycemia or traumatic brain injury have demonstrated positive pyruvate effects on memory function (Moro et al, 2011;Suh et al, 2005). We confirmed effects in short and long-term memory performances in treated 3xTg-AD mice.…”

Cortical Reorganization after Experimental Traumatic Brain Injury: A Functional Autoradiography Study

“…16 The absence of activation after CCI injury occurs when cerebral glucose metabolism has normalized in this model, 32 which suggests that either the region has become irreversibly damaged from ensuing tissue atrophy or other local injury mechanisms, or that the region has become chronically disconnected. Disconnection is more likely, because the injured ipsilesional cortex can, in fact, be locally activated by direct stimulation after fluid percussion injury.…”

Effect of Intraperitoneal Resuscitation With Different Concentrations of Sodium Pyruvate on Intestinal Ischemia Reperfusion Injury in Hemorrhagic Shock Rat

“…In a rat stroke model, pyruvate can regulate the expression of HIF1alpha and EPO in brain neuron and glial cells, activate AKT, reduce intracellular DNA cleavage, and relieve ischemia- reperfusion injury of brain. By enhancing glucose metabolism and oxidative phosphorylation, pyruvate can increase ATP generation and lower the degree of cognitive deficits after trauma (10,18). During the process of fluid resuscitation after HS, pyruvate can correct lactic acidosis (19), and improve the prognosis and survival rate (20).…”