Date of Award
Master of Arts
Previously, we have demonstrated that nicotinamide (NAm), a neuroprotective soluble B-group vitamin, improves recovery of function following traumatic brain injury (TBI). However, no prior studies have examined whether NAm is beneficial following continuous infusions over seven days post-TBI. The purpose of this study was to investigate the preclinical efficacy of NAm treatment as it might be delivered clinically; over several days by slow infusion. Rats were prepared with either unilateral controlled cortical impact (CCI) injuries over the somatosensory cortex (SMC) or sham procedures and divided into three groups: CCI-NAm, CCI-vehicle, and sham. Thirty minutes following CCI, Alzet osmotic mini-pumps were implanted subcutaneously. NAm was delivered at a rate of 50 mg/kg/day for seven days immediately post-CCI. On day seven following injury, the pumps were removed and blood draws were collected for serum NAm and nicotinamide adenine dinucleotide (NAD+) analyses. Starting on day two post-CCI, animals were tested on a battery of sensorimotor tests (bilateral tactile adhesive removal, locomotor placing, and limb-use asymmetry). Statistical analyses of the tactile removal and locomotor placing data revealed that continuous administration of NAm significantly reduced the initial magnitude of the injury deficit and improved overall recovery compared to the vehicle-treated animals. NAm treatment also significantly decreased limb-use asymmetry compared to vehicle-treated animals. Continuous infusion of NAm resulted in a significant serum elevation in NAm, but not NAD+, as well as significantly attenuated cortex tissue loss than un-treated animals. The NAm-treated group also had the lowest number of glial fibrillary acidic protein (GFAP) positive cells. No detrimental effects were seen following continuous infusion. The present results suggest that NAm delivered via a clinically relevant therapeutic regimen may truncate behavioral damage following TBI. Thus our results offer strong support for translation into the clinical population.
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