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

Michael R. Hoane, J. L. Pierce, M. A. Holland, G. D. Anderson

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Recent studies have demonstrated nicotinamide (NAM), a soluble B-group vitamin, to be an effective treatment in experimental models of traumatic brain injury (TBI). However, research on this compound has been limited to administration regimens starting shortly after injury. This study was conducted to establish the window of opportunity for NAM administration following controlled cortical impact (CCI) injury to the frontal cortex. Groups of rats were assigned to NAM (50 mg/kg), saline (1 ml/kg), or sham conditions and received contusion injuries or sham procedures. Injections of NAM or saline were administered at 15 min, 4 h, or 8 h post-injury, followed by five boosters at 24 h intervals. Following the last injection, blood was taken for serum NAM analysis. Animals were tested on a variety of tasks to assess somatosensory performance (bilateral tactile adhesive removal and vibrissae-forelimb placement) and cognitive performance (reference and working memory) in the Morris water maze. The results of the serum NAM analysis showed that NAM levels were significantly elevated in treated animals. Behavioral analysis on the tactile removal test showed that all NAM-treated groups facilitated recovery of function compared with saline treatment. On the vibrissae-forelimb placing test all NAM-treated groups also were significantly different from the saline-treated group. However, the acquisition of reference memory was only significantly improved in the 15-min and 4-h groups. In the working memory task both the 15-min and 4-h groups also improved working memory compared with saline treatment. The window of opportunity for NAM treatment is task-dependent and extends to 8 h for the sensorimotor tests but only extends to 4 h post-injury in the cognitive tests. These results suggest that a 50 mg/kg treatment regimen starting at the clinically relevant time point of 4 h may result in attenuated injury severity in the human TBI population.

Original languageEnglish (US)
Pages (from-to)861-868
Number of pages8
JournalNeuroscience
Volume154
Issue number3
DOIs
StatePublished - Jun 26 2008
Externally publishedYes

Fingerprint

Niacinamide
Wounds and Injuries
Short-Term Memory
Therapeutics
Vibrissae
Forelimb
Touch
Brain Contusion
Vitamin B Complex
Injections
Contusions
Recovery of Function
Frontal Lobe
Serum
Adhesives
Theoretical Models

Keywords

  • recovery of function
  • therapy
  • traumatic brain injury
  • vitamin
  • window of opportunity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Nicotinamide treatment induces behavioral recovery when administered up to 4 hours following cortical contusion injury in the rat. / Hoane, Michael R.; Pierce, J. L.; Holland, M. A.; Anderson, G. D.

In: Neuroscience, Vol. 154, No. 3, 26.06.2008, p. 861-868.

Research output: Contribution to journalArticle

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