Sex-Specific Differences in Rodents Following a Single Primary Blast Exposure: Focus on the Monoamine and Galanin Systems

Abstract

Most blast-induced traumatic brain injuries (bTBI) are mild in severity and culpable for the lingering and persistent neuropsychological complaints in affected individuals. There is evidence that the prevalence of symptoms post-exposure may be sex-specific. Our laboratory has focused on changes in the monoamine and the neuropeptide, galanin, systems in male rodents following primary bTBI. In this study, we aimed to replicate these findings in female rodents. Brainstem sections from the locus coeruleus (LC) and dorsal raphe nuclei (DRN) were processed for in situ hybridisation at 1 and 7 days post-bTBI. We investigated changes in the transcripts for tyrosine hydroxylase (TH), tryptophan hydroxylase two (TPH2) and galanin. Like in males, we found a transient increase in TH transcript levels bilaterally in the female LC. Changes in TPH2 mRNA were more pronounced and extensive in the DRN of females compared to males. Galanin mRNA was increased bilaterally in the LC and DRN, although this increase was not apparent until day 7 in the LC. Serum analysis revealed an increase in corticosterone, but only in exposed females. These changes occurred without any visible signs of white matter injury, cell death, or blood–brain barrier breakdown. Taken together, in the apparent absence of visible structural damage to the brain, the monoamine and galanin systems, two key players in emotional regulation, are activated deferentially in males and females following primary blast exposure. These similarities and differences should be considered when developing and evaluating diagnostic and therapeutic interventions for bTBI.

Repetitive Blast Exposure Increases Appetitive Motivation and Behavioral Inflexibility in Male Mice

“…While most blast-related research has been conducted only in male animal models, a growing number of females are now serving with military occupational specialty codes which, like their male colleagues, can entail increased risk for blast exposure (Iverson et al, 2011 ; Gray et al, 2020 ). Sex differences in relation to a single blast exposure have been previously reported (Russell et al, 2018a , b ; Kawa et al, 2020 ) and ongoing research is focused on comparing repetitive blast exposure in male and female mice. Further, here we assess behavioral outcomes to ~2 months post-blast, but these results may not extrapolate to more extreme timepoints and will require additional follow-up work focused on understanding blast mTBI outcomes in more aged populations.…”

Timing matters: Sex differences in acute and chronic outcomes following repetitive blast mild traumatic brain injury

“…Indeed, few preclinical studies have included both male and female animals and the few that have, have exclusively focused on impact TBI, a single TBI exposure, and/or only examined acute timepoints. While a handful of reports have characterized potential sex differences following a single blast exposure (Hubbard et al, 2022; Kawa et al, 2020; McNamara et al, 2022; Russell, Handa, et al, 2018; Russell, Richardson, et al, 2018), very little is known about the effects of repetitive blast exposure in male vs. female rodents.…”