Abstract |
Neuroprotection, recovery of function, and gene expression were evaluated in an animal model of traumatic brain injury (TBI) after a combination treatment of nicotinamide (NAM) and progesterone (Prog). Animals received a cortical contusion injury over the sensorimotor cortex, and were treated with either Vehicle, NAM, Prog, or a NAM/Prog combination for 72 h and compared with a craniotomy only ( Sham) group. Animals were assessed in a battery of behavioral, sensory, and both fine and gross motor tasks, and given histological assessments at 24 h post-injury to determine lesion cavity size, degenerating neurons, and reactive astrocytes. Microarray-based transcriptional profiling was used to determine treatment-specific changes on gene expression. Our results confirm the beneficial effects of treatment with either NAM or Prog, demonstrating significant improvements in recovery of function and a reduction in lesion cavitation, degenerating neurons, and reactive astrocytes 24 h post-injury. The combination treatment of NAM and Prog led to a significant improvement in both neuroprotection at 24 h post-injury and recovery of function in sensorimotor related tasks when compared with individual treatments. The NAM/Prog-treated group was the only treatment group to show a significant reduction of cortical loss 24 h post-injury. The combination appears to affect inflammatory and immune processes, reducing expression of a significant number of genes in both pathways. Further preclinical trials using NAM and Prog as a combination treatment should be conducted to identify the window of opportunity, determine the optimal duration of treatment, and evaluate the combination in other pre-clinical models of TBI.
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Authors | Todd C Peterson, Michael R Hoane, Keith S McConomy, Fred M Farin, Theo K Bammler, James W MacDonald, Eric D Kantor, Gail D Anderson |
Journal | Journal of neurotrauma
(J Neurotrauma)
Vol. 32
Issue 11
Pg. 765-79
(Jun 01 2015)
ISSN: 1557-9042 [Electronic] United States |
PMID | 25313690
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Chemical References |
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Topics |
- Animals
- Brain Injuries
(drug therapy, genetics, pathology)
- Drug Therapy, Combination
- Male
- Niacinamide
(administration & dosage)
- Progesterone
(administration & dosage)
- Rats
- Rats, Sprague-Dawley
- Recovery of Function
(drug effects, genetics)
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