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.
Highlights
Blast-induced traumatic brain injury is prevalent in active combat, terror attacks are increasingly putting civilians at risk of similar brain injuries [1, 2]
We have previously reported on the effect of a single primary blast exposure on the behaviour of male rats and changes to the monoaminergic and galanin systems across various brain regions and time points using a blast tube [47, 48] and confirmed that these changes are robust in another model of primary blast TBI, the shock tube [49]
Female rats were weighed daily, a week before and after the primary blast exposure, and no significant differences in body weight were found between sham and exposed groups throughout the experiment (Figure 1A)
Summary
Blast-induced traumatic brain injury (bTBI) is prevalent in active combat, terror attacks are increasingly putting civilians at risk of similar brain injuries [1, 2] Of those with a positive TBI screen, the significant majority are mild in severity but may still confer increased risk of developing mood and anxiety disorders [3, 4]. Research into such post-trauma sequelae has predominantly focused on male subjects, in animal and clinical studies alike.
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