Nicotinamide treatment provides acute neuroprotection and GFAP regulation following fluid percussion injury

Michael A. Holland, Arlene A. Tan, Douglas C. Smith, Michael R. Hoane

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Previous studies in our laboratory have demonstrated the preclinical efficacy of nicotinamide (NAM; vitamin B3) treatment following fluid percussion injury (FPI). At a dose of 500 or 50 mg/kg, NAM significantly facilitated recovery of function on a variety of motor and sensorimotor tasks in rodents, and the 500 mg/kg dose improved cognitive performance. The purpose of the present study was to examine the acute neuroprotective ability of NAM following FPI. Rats were given a moderate FPI (1.8 atm) or sham injury. NAM (500 or 50 mg/kg) or saline was administered 15 min and 20 h after FPI. Rats were sacrificed at 24 h or 7 days following injury and prepared for histological analysis. Systematic volumetric measurements were conducted to examine cortical loss in a series of cresyl violet stained slices to examine the development of the injury cavity. To assess the extent of astrocytic activity and neurodegeneration, triple labeling with glial fibrillary acidic protein (GFAP), Fluoro-Jade B (FJ), and DAPI was performed. GFAP+ astrocytes and FJ+ neurons in the ipsilateral and contralateral cortex, and ipsilateral hippocampus and thalamus were assessed. While not significant at 24 h, NAM significantly attenuated cortical tissue loss at 7 days. At 24 h, the number of GFAP+ astrocytes was significantly reduced by NAM. However, the inverse was observed at 7 days where NAM treatment significantly increased the number of GFAP+ astrocytes. Both doses of NAM also significantly reduced FJ expression at the 24-h and 7-day time intervals. The results of this study suggest that NAM has strong neuroprotective abilities in the injured brain and may have therapeutic potential for brain injury.

Original languageEnglish (US)
Pages (from-to)140-152
Number of pages13
JournalJournal of Neurotrauma
Volume25
Issue number2
DOIs
StatePublished - Feb 1 2008
Externally publishedYes

    Fingerprint

Keywords

  • Fluoro-jade
  • GFAP
  • Neuroprotection
  • Nicotinamide
  • Therapy
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this