A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury
| Autor: | Gail D. Anderson, Eric D. Kantor, James W. MacDonald, Fred M. Farin, Michael R. Hoane, Keith S. McConomy, Todd C. Peterson, Theo K. Bammler |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Niacinamide Pathology medicine.medical_specialty Combination therapy Microarray Traumatic brain injury medicine.medical_treatment Sensory system Neuroprotection Rats Sprague-Dawley Lesion chemistry.chemical_compound Animals Medicine Progesterone Craniotomy Nicotinamide business.industry Original Articles Recovery of Function medicine.disease Rats chemistry Brain Injuries Anesthesia Drug Therapy Combination Neurology (clinical) medicine.symptom business |
| Zdroj: | Journal of Neurotrauma. 32:765-779 |
| ISSN: | 1557-9042 0897-7151 |
| DOI: | 10.1089/neu.2014.3530 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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