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Sustained Delivery of Nicotinamide Limits Cortical Injury and Improves Functional Recovery Following Traumatic Brain Injury
- Source :
- Oxidative Medicine and Cellular Longevity, Vol 3, Iss 2, Pp 145-152 (2010), Oxidative Medicine and Cellular Longevity
- Publication Year :
- 2010
- Publisher :
- Hindawi Limited, 2010.
-
Abstract
- 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 7 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 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 7 days immediately post-CCI. On day 7 following injury, the pumps were removed and blood draws were collected for serum NAM and nicotinamide adenine dinucleotide (NAD+) analyses. Starting on day 2 post-CCI, animals were tested on a battery of sensorimotor tests (bilateral tactile adhesive removal, locomotor placing and limb-use asymmetry). Continuous infusion of NAM resulted in a significant serum elevation in NAM, but not NAD+. 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 asymmetries compared to vehicle-treated animals. The overall extent of the cortical damage was also reduced by NAM treatment. 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.
- Subjects :
- Male
Niacinamide
Vitamin
Aging
animal structures
Traumatic brain injury
Population
Biochemistry
Neuroprotection
Drug Administration Schedule
Rats, Sprague-Dawley
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Restorative neurology
Animals
Medicine
lcsh:QH573-671
education
health care economics and organizations
030304 developmental biology
Cerebral Cortex
neurorehabilitation
therapy
0303 health sciences
education.field_of_study
restorative neurology
Nicotinamide
behavior
business.industry
lcsh:Cytology
food and beverages
Cell Biology
General Medicine
brain injury
medicine.disease
Research Papers
Rats
3. Good health
chemistry
Brain Injuries
Anesthesia
Vitamin B Complex
NAD+ kinase
business
030217 neurology & neurosurgery
Blood drawing
Subjects
Details
- Language :
- English
- ISSN :
- 19420994 and 19420900
- Volume :
- 3
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....2e456337439792f5bcad0b7f9ecfba09