A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury

Todd C. Peterson, Michael R. Hoane, Keith S. Mcconomy, Fred M. Farin, Theo K. Bammler, James W. MacDonald, Eric D. Kantor, Gail D. Anderson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)765-779
Number of pages15
JournalJournal of Neurotrauma
Volume32
Issue number11
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

Fingerprint

Niacinamide
Progesterone
Recovery of Function
Wounds and Injuries
Astrocytes
Therapeutics
Gene Expression
Neurons
Craniotomy
Traumatic Brain Injury
Animal Models
Genes

Keywords

  • Controlled cortical impact
  • Nicotinamide
  • Polytherapy
  • Progesterone
  • Recovery of function
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Peterson, T. C., Hoane, M. R., Mcconomy, K. S., Farin, F. M., Bammler, T. K., MacDonald, J. W., ... Anderson, G. D. (2015). A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury. Journal of Neurotrauma, 32(11), 765-779. https://doi.org/10.1089/neu.2014.3530

A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury. / Peterson, Todd C.; Hoane, Michael R.; Mcconomy, Keith S.; Farin, Fred M.; Bammler, Theo K.; MacDonald, James W.; Kantor, Eric D.; Anderson, Gail D.

In: Journal of Neurotrauma, Vol. 32, No. 11, 01.06.2015, p. 765-779.

Research output: Contribution to journalArticle

Peterson, TC, Hoane, MR, Mcconomy, KS, Farin, FM, Bammler, TK, MacDonald, JW, Kantor, ED & Anderson, GD 2015, 'A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury', Journal of Neurotrauma, vol. 32, no. 11, pp. 765-779. https://doi.org/10.1089/neu.2014.3530
Peterson, Todd C. ; Hoane, Michael R. ; Mcconomy, Keith S. ; Farin, Fred M. ; Bammler, Theo K. ; MacDonald, James W. ; Kantor, Eric D. ; Anderson, Gail D. / A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury. In: Journal of Neurotrauma. 2015 ; Vol. 32, No. 11. pp. 765-779.
@article{548397b2d3984e89bee282681357454b,
title = "A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury",
abstract = "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.",
keywords = "Controlled cortical impact, Nicotinamide, Polytherapy, Progesterone, Recovery of function, Traumatic brain injury",
author = "Peterson, {Todd C.} and Hoane, {Michael R.} and Mcconomy, {Keith S.} and Farin, {Fred M.} and Bammler, {Theo K.} and MacDonald, {James W.} and Kantor, {Eric D.} and Anderson, {Gail D.}",
year = "2015",
month = "6",
day = "1",
doi = "10.1089/neu.2014.3530",
language = "English (US)",
volume = "32",
pages = "765--779",
journal = "Journal of Neurotrauma",
issn = "0897-7151",
publisher = "Mary Ann Liebert Inc.",
number = "11",

}

TY - JOUR

T1 - A Combination Therapy of Nicotinamide and Progesterone Improves Functional Recovery following Traumatic Brain Injury

AU - Peterson, Todd C.

AU - Hoane, Michael R.

AU - Mcconomy, Keith S.

AU - Farin, Fred M.

AU - Bammler, Theo K.

AU - MacDonald, James W.

AU - Kantor, Eric D.

AU - Anderson, Gail D.

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.

AB - 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.

KW - Controlled cortical impact

KW - Nicotinamide

KW - Polytherapy

KW - Progesterone

KW - Recovery of function

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=84930317060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84930317060&partnerID=8YFLogxK

U2 - 10.1089/neu.2014.3530

DO - 10.1089/neu.2014.3530

M3 - Article

VL - 32

SP - 765

EP - 779

JO - Journal of Neurotrauma

JF - Journal of Neurotrauma

SN - 0897-7151

IS - 11

ER -