Effect of lactate therapy upon cognitive deficits after traumatic brain injury in the rat

Background. In previous studies, it has been shown that intravenous lactate therapy can improve brain neurochemistry, adenosine triphosphate (ATP) generation and outcome after traumatic brain injury (TBI) in rats. In this study, we examined: (1) four L-lactate concentrations to determine the optimal therapeutic dose post TBI in terms of cognitive function; (2) ATP production after TBI for the L-lactate concentration found to be the optimal dose; (3) the possible production of lactic acidosis with the highest L-lactate concentration tested. Methods. Thirty minutes following a fluid percussion injury (FPI) over the left cerebral hemisphere, the animals received an intravenous infusion of 10, 28, 100, or 280mM L-lactate (n = 10 for each group) for 3h at a rate of 0.65ml/h. Shams and control injured animals received a saline infusion. At 11-15 days post injury, cognitive deficits were examined using the Morris Water Maze (MWM) test. Three groups of rats were used for ATP analysis: shams, injured + saline infusion, and injury + the optimal lactate dose as determined by the MWM (n = 4/group). Additionally, a group receiving 280mM L-lactate (n = 5) and one receiving a saline infusion (n = 3) were monitored for arterial blood variables and blood pressures. Findings. In the MWM test, only the 100mM L-lactate-treated injured animals showed a significant reduction in cognitive deficits when compared to saline-treated injured animals (p n 0.05). In the ATP study, injured animals without treatment had a 53% reduction in ATP level in the ipsilateral cortex, while animals with 100mM lactate treatment had a 28% reduction. (p n 0.05). No lactic acidosis was induced by the intravenous infusion of 280mM L-lactate. Conclusions. This study indicates that the intravenous infusion of 100mM L-lactate provided the optimal concentration of the substrate to ameliorate cognitive impairment, probably via the regeneration of ATP following TBI in rats.