Administration of diphenyl diselenide (PhSe)2 following repetitive mild traumatic brain injury exacerbates anxiety-like symptomology in a rat model

Abstract

Approximately 10–15 % of people that sustain mild traumatic brain injury (mTBI) develop post-concussive syndrome (PCS). PCS is a complex array of symptoms that can result in physical, cognitive and emotional impairments. Following mTBI, there are also complex changes in the oxidative stress system and engagement of the inflammatory system, within the brain. Diphenyl diselenide (PhSe)2 is an organoselenium compound which can play a role in anti-oxidant and anti-inflammatory activities. (PhSe)2 also has many interesting properties including anti-anxiety, anti-depressant and anti-nociception effects. We sought to determine if treatment with (PhSe)2 following repetitive mTBI could have mitigating effects on PCS. To investigate this, we induced mTBI or sham injuries using our lateral impact device in adolescent male and female Sprague Dawley rats and an hour later injected rats with vehicle, 10 mg/kg or 25 mg/kg (PhSe)2 i.p. Next, we conducted a behavioral assessment designed to assess PCS and then euthanized the animals to examine changes in gene expression and telomere length. (PhSe)2 decreased the time to cross the beam, distance travelled and time spent in the centre of the open field, time spent in the open arms of the elevated plus maze, the time investigating both objects in the novel context mismatch and time immobile in the forced swim. This anxiety-like symptomology resolved spontaneously between 10 and 12 days after the third mTBI. We found (PhSe)2 groups showed increased levels of TNF alpha and longer telomeres. We also found higher levels of GPX1 in the injured animals. Our results show that (PhSe)2 exacerbates anxiety-like symptomology in contrast to previous findings.