EFFECTS OF PRE- VS. POST-TBI CANNABIDIOL ON EXPRESSION OF A NEUROINFLAMMATORY MARKER IN MALE AND FEMALE ZEBRA FINCHES

Abstract

Traumatic brain injuries (TBIs) cause significant morbidity through primary and secondary mechanisms, the latter involving chronic neuroinflammation from persistent microglial activation. Current treatments (e.g., NSAIDs, glucocorticoids) for chronic neuroinflammation have dose-limiting side-effects, and therefore potential anti-inflammatory alternatives, like cannabidiol (CBD) are being investigated. Songbirds like zebra finches are an ideal model for studying functional recovery following TBI, as their song development and associated neural circuitry share well-documented parallels with human speech acquisition and sensorimotor learning. Prior studies in male zebra finches showed CBD treatments pre-TBI (7 days) reduces neuroinflammation and accelerates vocal recovery. But key questions about post-injury efficacy and sex differences remain untested. As females don’t sing, we used IL1β transcription, a neuroinflammation marker, via qRT-PCR to assess CBD’s effects across sexes. We hypothesized that post-TBI CBD (10 mg/kg, short or long treatment) would decrease IL1β transcription following HVC lesions, with potential sex differences given some evidence for a neuroprotective role for female hormones1–9. Male and female zebra finches received unilateral HVC microlesions, with CBD or vehicle given pre- (7 days) or post-injury (2 days). No statistically significant differences emerged across drug, treatment timing, or sex (three-way ANOVA, p > 0.05). However, males showed a trend toward reduced IL1β with short-term CBD (despite variability). Females exhibited wider spread in IL1β expression levels, possibly reflecting hormonal effects. A larger sample size and better optimization of experimental conditions might reveal significant trends, including previously noted male efficacy. This study highlights CBD’s potential post-TBI efficacy and the need to explore sex-specific responses.