TY - JOUR
T1 - Continuous nicotinamide administration improves behavioral recovery and reduces lesion size following bilateral frontal controlled cortical impact injury
AU - Vonder Haar, Cole
AU - Anderson, Gail D.
AU - Hoane, Michael R.
N1 - Funding Information:
The authors would like to thank Andrew Vaz for his help with behavioral data collection and scoring and Michael Emery and Kris Martens for assisting in surgical procedures. Funding for this project was provided by ARRA funds from NINDS grant NS045647-04 and NIH/NICHD grant HD061944-01 .
PY - 2011/10/31
Y1 - 2011/10/31
N2 - Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B 3) in animal models of TBI with systemic dosing at 50 and 500mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150mg/kgday) or saline (1ml/kg) pumps 30min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies.
AB - Previous research has demonstrated considerable preclinical efficacy of nicotinamide (NAM; vitamin B 3) in animal models of TBI with systemic dosing at 50 and 500mg/kg yielding improvements on sensory, motor, cognitive and histological measures. The current study aimed to utilize a more specific dosing paradigm in a clinically relevant delivery mechanism: continuously secreting subcutaneous pumps. A bilateral frontal controlled cortical impact (CCI) or sham surgery was performed and rats were treated with NAM (150mg/kgday) or saline (1ml/kg) pumps 30min after CCI, continuing until seven days post-CCI. Rats were given a loading dose of NAM (50mg/kg) or saline (1ml/kg) following pump implant. Rats received behavioral testing (bilateral tactile adhesive removal, locomotor placing task and Morris water maze) starting on day two post-CCI and were sacrificed at 31 days post-CCI and brains were stained to examine lesion size. NAM-treated rats had reductions in sensory, motor and cognitive behavioral deficits compared to vehicle-treated rats. Specifically, NAM-treated rats significantly improved on the bilateral tactile adhesive removal task, locomotor placing task and the reference memory paradigm of the Morris water maze. Lesion size was also significantly reduced in the NAM-treated group. The results from this study indicate that at the current dose, NAM produces beneficial effects on recovery from a bilateral frontal brain injury and that it may be a relevant compound to be explored in human studies.
KW - Rat
KW - Recovery of function
KW - Traumatic brain injury
KW - Treatment
KW - Vitamin B
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U2 - 10.1016/j.bbr.2011.06.009
DO - 10.1016/j.bbr.2011.06.009
M3 - Article
C2 - 21704653
AN - SCOPUS:80051784028
SN - 0166-4328
VL - 224
SP - 311
EP - 317
JO - Behavioural Brain Research
JF - Behavioural Brain Research
IS - 2
ER -