Treatment with Vitamin B₃ Improves Functional Recovery and Reduces GFAP Expression following Traumatic Brain Injury in Rats

Abstract

Previous studies have shown that administration of vitamin B(3) (B(3)) in animal models of ischemia significantly reduced the size of infarction and improved functional recovery. The present study evaluated the effect of administration of B(3) on recovery of function following traumatic brain injury (TBI), incorporating the bilateral medial frontal cortex contusion injury model. Groups of rats were assigned to B(3) (500 mg/kg) or saline (1.0 ml/kg) treatment conditions and received contusion injuries or sham surgeries. Drug treatment was administered 15 min and 24 h following injury. Rats were examined on a variety of tests to measure sensorimotor performance (bilateral tactile adhesive removal), skilled forelimb use (staircase test), and cognitive ability (reference and working memory) in the Morris Water Maze. Administration of B(3) following injury significantly reduced the behavioral impairments observed on the bilateral tactile removal test, but not on skilled forelimb use. The acquisition of reference and working memory tests were also significantly improved compared to saline-treated rats. Examination of the brains revealed that administration of B(3) significantly reduced the size of the lesion compared to treatment with saline. In addition, examination of glial fibrillary acidic protein (GFAP) expression around the lesion revealed that B(3) significantly reduced the number of GFAP(+) astrocytes. These results indicate that B(3) administration significantly improved behavioral outcome following injury, reduced the size of the lesion, and reduced the expression of GFAP. The current findings suggest that B(3) may have therapeutic potential for the treatment of TBI.

Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat

“…The CCI model utilized in the present study was based on previous studies (Hoane et al, 2003). Animals were anesthetized using a mixture of Isoflurane (5 − 2.5 %) and oxygen (0.8 L/min).…”

“…This test has been previously shown to be a sensitive assessment of somatosensory and attentional deficits following injury to the frontal lobes and has been described in detail (Schallert et al, 2000, Hoane et al, 2003, Schallert and Woodlee, 2005, Hoane et al, 2006c, Hoane et al, 2007. A slightly modified version of this task was used in this experiment.…”

“…The MWM has been widely utilized to assess cognitive performance following brain injury (Lindner et al, 1998, Hoane et al, 2003. A 1.5 m diameter blue fiberglass pool was filled with water (24°C) to a depth of 32 cm and a 10 cm 2 clear Plexiglas platform was submerged 1 cm below the surface of the water.…”

“…Hoane, Akstulewicz, & Toppen (2003) showed that NAM was effective at improving behavioral and histological outcome following TBI. Animals received bilateral cortical contusion injury (CCI) to the medial prefrontal cortex and were administered NAM (500 mg/kg) at 15 min with a booster at 24 hrs post-injury.…”

“…Behavioral evaluation revealed that NAM-treated animals were significantly less impaired than saline-treated animals in sensorimotor (bilateral tactile adhesive removal task) and cognitive measures (Morris water maze). NAM was also shown to decrease the size of the lesion cavity and down regulate the glial response (Hoane et al, 2003).…”