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

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.