Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury

Cole Vonder Haar, Gail D. Anderson, Michael R. Hoane

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B 3) in animal models of TBI with systemic dosing at 50 and 500mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150mg/kgday) or saline (1ml/kg) pumps 30min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies.

Original languageEnglish (US)
Pages (from-to)311-317
Number of pages7
JournalBehavioural Brain Research
Volume224
Issue number2
DOIs
StatePublished - Oct 31 2011
Externally publishedYes

Keywords

  • Rat
  • Recovery of function
  • Traumatic brain injury
  • Treatment
  • Vitamin B

ASJC Scopus subject areas

  • Behavioral Neuroscience

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