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.
journal_name
J Neurotraumajournal_title
Journal of neurotraumaauthors
Peterson TC,Hoane MR,McConomy KS,Farin FM,Bammler TK,MacDonald JW,Kantor ED,Anderson GDdoi
10.1089/neu.2014.3530subject
Has Abstractpub_date
2015-06-01 00:00:00pages
765-79issue
11eissn
0897-7151issn
1557-9042journal_volume
32pub_type
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
pub_type: 杂志文章,评审
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更新日期:2012-11-20 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.1996.13.465
更新日期:1996-08-01 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2015.4237
更新日期:2016-10-15 00:00:00
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journal_title:Journal of neurotrauma
pub_type: 杂志文章
doi:10.1089/neu.2007.0477
更新日期:2008-06-01 00:00:00
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journal_title:Journal of neurotrauma
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更新日期:2013-07-15 00:00:00
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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journal_title:Journal of neurotrauma
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