Effects of nicotinamide on spatial memory and inflammation after juvenile traumatic brain injury

Aidan C. Smith, Ryan C. Holden, Sherry M. Rasmussen, Michael R. Hoane, Michael J. Hylin

Research output: Contribution to journalArticle

Abstract

Age is a consistent predictor of outcome following traumatic brain injury (TBI). Although children and adolescents have the highest rate of hospitalizations and long-term disabilities, few preclinical studies have attempted to model and treat TBI in this population. Studies using nicotinamide (NAM), a soluble B-group vitamin, in older animals (3–6 months) have shown improved functional recovery in experimental models of TBI. The purpose of this study was two-fold: to examine the preclinical efficacy of NAM at different doses on behavioral outcomes in juvenile rats and examine the microglial response over time. Groups of juvenile rats (PND 28–60) were assigned to sham, NAM (125 mg/kg, 500 mg/kg, or 1000 mg/kg) or saline (1 mL/kg) and received unilateral cortical contusion injuries (CCI) and received injections at 15 min, 24 h, and 72 h after injury. Animals treated with NAM demonstrated no significant behavioral improvements over saline treatments. NAM treatments did however show slowed cortical loss and reduced microglia compared to saline treated animals. In summary, the preclinical efficacy of NAM as a treatment following CCI in juvenile animals differs from that previously documented in older rat models. While NAM treatments did reduce microglial activity and slowed progression of cortical loss, it did not reduce the total cortical volume lost nor did it improve behavioral outcomes. The findings of this study emphasize the need to examine potential treatments for TBI utilizing juvenile populations and may explain why so many treatments have failed in clinical trials.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalBehavioural Brain Research
Volume364
DOIs
StatePublished - May 17 2019
Externally publishedYes

Fingerprint

Niacinamide
Inflammation
Wounds and Injuries
Therapeutics
Vitamin B Complex
Microglia
Traumatic Brain Injury
Spatial Memory
Population
Hospitalization
Theoretical Models
Clinical Trials
Injections

Keywords

  • Functional recovery
  • Inflammation
  • Juvenile
  • Nicotinamide
  • Traumatic brain injury

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Effects of nicotinamide on spatial memory and inflammation after juvenile traumatic brain injury. / Smith, Aidan C.; Holden, Ryan C.; Rasmussen, Sherry M.; Hoane, Michael R.; Hylin, Michael J.

In: Behavioural Brain Research, Vol. 364, 17.05.2019, p. 123-132.

Research output: Contribution to journalArticle

Smith, Aidan C. ; Holden, Ryan C. ; Rasmussen, Sherry M. ; Hoane, Michael R. ; Hylin, Michael J. / Effects of nicotinamide on spatial memory and inflammation after juvenile traumatic brain injury. In: Behavioural Brain Research. 2019 ; Vol. 364. pp. 123-132.
@article{3f278756ee0b42c4b1d1c812eb305ceb,
title = "Effects of nicotinamide on spatial memory and inflammation after juvenile traumatic brain injury",
abstract = "Age is a consistent predictor of outcome following traumatic brain injury (TBI). Although children and adolescents have the highest rate of hospitalizations and long-term disabilities, few preclinical studies have attempted to model and treat TBI in this population. Studies using nicotinamide (NAM), a soluble B-group vitamin, in older animals (3–6 months) have shown improved functional recovery in experimental models of TBI. The purpose of this study was two-fold: to examine the preclinical efficacy of NAM at different doses on behavioral outcomes in juvenile rats and examine the microglial response over time. Groups of juvenile rats (PND 28–60) were assigned to sham, NAM (125 mg/kg, 500 mg/kg, or 1000 mg/kg) or saline (1 mL/kg) and received unilateral cortical contusion injuries (CCI) and received injections at 15 min, 24 h, and 72 h after injury. Animals treated with NAM demonstrated no significant behavioral improvements over saline treatments. NAM treatments did however show slowed cortical loss and reduced microglia compared to saline treated animals. In summary, the preclinical efficacy of NAM as a treatment following CCI in juvenile animals differs from that previously documented in older rat models. While NAM treatments did reduce microglial activity and slowed progression of cortical loss, it did not reduce the total cortical volume lost nor did it improve behavioral outcomes. The findings of this study emphasize the need to examine potential treatments for TBI utilizing juvenile populations and may explain why so many treatments have failed in clinical trials.",
keywords = "Functional recovery, Inflammation, Juvenile, Nicotinamide, Traumatic brain injury",
author = "Smith, {Aidan C.} and Holden, {Ryan C.} and Rasmussen, {Sherry M.} and Hoane, {Michael R.} and Hylin, {Michael J.}",
year = "2019",
month = "5",
day = "17",
doi = "10.1016/j.bbr.2019.02.024",
language = "English (US)",
volume = "364",
pages = "123--132",
journal = "Behavioural Brain Research",
issn = "0166-4328",
publisher = "Elsevier",

}

TY - JOUR

T1 - Effects of nicotinamide on spatial memory and inflammation after juvenile traumatic brain injury

AU - Smith, Aidan C.

AU - Holden, Ryan C.

AU - Rasmussen, Sherry M.

AU - Hoane, Michael R.

AU - Hylin, Michael J.

PY - 2019/5/17

Y1 - 2019/5/17

N2 - Age is a consistent predictor of outcome following traumatic brain injury (TBI). Although children and adolescents have the highest rate of hospitalizations and long-term disabilities, few preclinical studies have attempted to model and treat TBI in this population. Studies using nicotinamide (NAM), a soluble B-group vitamin, in older animals (3–6 months) have shown improved functional recovery in experimental models of TBI. The purpose of this study was two-fold: to examine the preclinical efficacy of NAM at different doses on behavioral outcomes in juvenile rats and examine the microglial response over time. Groups of juvenile rats (PND 28–60) were assigned to sham, NAM (125 mg/kg, 500 mg/kg, or 1000 mg/kg) or saline (1 mL/kg) and received unilateral cortical contusion injuries (CCI) and received injections at 15 min, 24 h, and 72 h after injury. Animals treated with NAM demonstrated no significant behavioral improvements over saline treatments. NAM treatments did however show slowed cortical loss and reduced microglia compared to saline treated animals. In summary, the preclinical efficacy of NAM as a treatment following CCI in juvenile animals differs from that previously documented in older rat models. While NAM treatments did reduce microglial activity and slowed progression of cortical loss, it did not reduce the total cortical volume lost nor did it improve behavioral outcomes. The findings of this study emphasize the need to examine potential treatments for TBI utilizing juvenile populations and may explain why so many treatments have failed in clinical trials.

AB - Age is a consistent predictor of outcome following traumatic brain injury (TBI). Although children and adolescents have the highest rate of hospitalizations and long-term disabilities, few preclinical studies have attempted to model and treat TBI in this population. Studies using nicotinamide (NAM), a soluble B-group vitamin, in older animals (3–6 months) have shown improved functional recovery in experimental models of TBI. The purpose of this study was two-fold: to examine the preclinical efficacy of NAM at different doses on behavioral outcomes in juvenile rats and examine the microglial response over time. Groups of juvenile rats (PND 28–60) were assigned to sham, NAM (125 mg/kg, 500 mg/kg, or 1000 mg/kg) or saline (1 mL/kg) and received unilateral cortical contusion injuries (CCI) and received injections at 15 min, 24 h, and 72 h after injury. Animals treated with NAM demonstrated no significant behavioral improvements over saline treatments. NAM treatments did however show slowed cortical loss and reduced microglia compared to saline treated animals. In summary, the preclinical efficacy of NAM as a treatment following CCI in juvenile animals differs from that previously documented in older rat models. While NAM treatments did reduce microglial activity and slowed progression of cortical loss, it did not reduce the total cortical volume lost nor did it improve behavioral outcomes. The findings of this study emphasize the need to examine potential treatments for TBI utilizing juvenile populations and may explain why so many treatments have failed in clinical trials.

KW - Functional recovery

KW - Inflammation

KW - Juvenile

KW - Nicotinamide

KW - Traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=85061543686&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061543686&partnerID=8YFLogxK

U2 - 10.1016/j.bbr.2019.02.024

DO - 10.1016/j.bbr.2019.02.024

M3 - Article

VL - 364

SP - 123

EP - 132

JO - Behavioural Brain Research

JF - Behavioural Brain Research

SN - 0166-4328

ER -