Poster abstracts
Poster number 77 submitted by Kristen Pechacek
Microglia turnover at 14 days post injury fails to recover traumatic brain injury-induced impulsivity and inattention
Kristen Pechacek (The Ohio State University), Anna Gaughan (The Ohio State University), Sarah Wampler (The Ohio State University), Noah Bressler (The Ohio State University), Rishi Panchal (The Ohio State University), Cole Vonder Haar (The Ohio State University, Chronic Brain Injury Group)
Abstract:
Traumatic brain injury (TBI) results in chronic psychiatric deficits including impulsivity and impairments in attention. Following TBI microglia propagate a chronic neuroinflammatory response that lasts years after the initial event and is linked to increases in psychiatric conditions. BLZ945, a CSF1R inhibitor, both depletes microglia and decreases the proinflammatory response of microglia after repopulation. The goal of this study was to deplete and repopulate (turnover) microglia at day 14 post injury to see if this reduced TBI-induced impulsivity and attentional deficits. Male and female rats were trained on the five-choice serial reaction time task (5CSRTT), an operant task that measures impulsivity and attention. Animals received bilateral, frontal controlled cortical impact injury or sham control. After seven days of recovery, rats resumed behavioral testing. At 13 days post injury rats received two doses of either BLZ945 (60 mg/kg) or vehicle 24 h apart. Behavioral testing continued for 10 additional weeks. Prior to TBI, male and female rat behavior did not differ on the 5CSRTT (p’s > 0.05). TBI increased both impulsivity and inattention in rats, but males and females were not differentially changed by TBI (p’s > 0.05). BLZ945 depleted 87% of microglia within 24h of the last dose. Microglia turnover with BLZ945 did not attenuate post-TBI impulsivity or attention deficits in male or female rats (p’s > 0.05). To better understand the underlying mechanisms behind the microglia turnover process we are conducting single nucleus RNA sequencing in the nucleus accumbens to determine how neurons and plasticity factors are changed following TBI.
Keywords: Traumatic Brain Injury, Impulsivity , Attention