The Effects of Hypertonic Saline and Nicotinamide on Sensorimotor and Cognitive Function Following Cortical Contusion Injury in the Rat

Hypertonic saline (HTS) is an accepted treatment for traumatic brain injury (TBI). However, the behavioral and cognitive consequences following HTS administration have not thoroughly been examined. Recent preclinical evidence has suggested that nicotinamide (NAM) is beneficial for recovery of function following TBI. The current study compared the behavioral and cognitive consequences of HTS and NAM as competitive therapeutic agents for the treatment of TBI. Following controlled cortical impact (CCI), bolus administrations of NAM (500 mg/kg), 7.5% HTS, or 0.9% saline vehicle (1.0 mL/kg) were given at 2, 24, and 48 hrs post-CCI. Behavioral results revealed that animals treated with NAM and HTS showed significant improvements in beam walk and locomotor placing compared to the Vehicle group. The Morris water maze (MWM) retrograde amnesia test was conducted on day 12 post-CCI and showed that all groups had significant retention of memory compared to injured, Vehicle-treated animals. Working memory was also assessed on days 18-20 using the MWM. The NAM and Vehicle groups quickly acquired the task; however, HTS animals showed no acquisition of this task. Histological examinations revealed that the HTS-treated animals lost significantly more cortical tissue than either the NAM or Vehicle-treated animals. HTS-treated animals showed a greater loss of hippocampal tissue compared to the other groups. In general, NAM showed a faster rate of recovery than HTS without this associated tissue loss. The results of this study reiterate the strengths of NAM following injury and show concerns with bolus administrations of HTS due to the differential effects on cognitive performance and apparent tissue loss.