Investigating the cumulative effects of Δ9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats.
Dhyey BhattAli HazariGlenn R YamakawaSabrina SalbergMarissa SgroSandy R ShultzRichelle MychasiukPublished in: Brain communications (2020)
The prevalence of mild traumatic brain injury is highest amongst the adolescent population and can lead to complications including neuroinflammation and excitotoxicity. Also pervasive in adolescents is recreational cannabis use. Δ9-Tetrahydrocannabinol, the main psychoactive component of cannabis, is known to have anti-inflammatory properties and serves as a neuroprotective agent against excitotoxicity. Thus, we investigated the effects of Δ9-tetrahydrocannabinol on recovery when administered either prior to or following repeated mild brain injuries. Male and female Sprague-Dawley rats were randomly assigned to receive Δ9-tetrahydrocannabinol or vehicle either prior to or following the repeated injuries. Rats were then tested on a behavioural test battery designed to measure post-concussive symptomology. The hippocampus, nucleus accumbens and prefrontal cortex were extracted from all animals to examine mRNA expression changes (Bdnf, Cnr1, Comt, GR, Iba-1 and Vegf-2R). We hypothesized that, in both experiments, Δ9-tetrahydrocannabinol administration would provide neuroprotection against mild injury outcomes and confer therapeutic benefit. Δ9-Tetrahydrocannabinol administration following repeated mild traumatic brain injury was beneficial to three of the six behavioural outcomes affected by injury (reducing anxiety and depressive-like behaviours while also mitigating injury-induced deficits in short-term working memory). Δ9-Tetrahydrocannabinol administration following injury also showed beneficial effects on the expression of Cnr1, Comt and Vegf-2R in the hippocampus, nucleus accumbens and prefrontal cortex. There were no notable benefits of Δ9-tetrahydrocannabinol when administered prior to injury, suggesting that Δ9-tetrahydrocannabinol may have potential therapeutic benefit on post-concussive symptomology when administered post-injury, but not pre-injury.
Keyphrases
- mild traumatic brain injury
- prefrontal cortex
- working memory
- young adults
- cerebral ischemia
- endothelial cells
- risk factors
- traumatic brain injury
- mental health
- poor prognosis
- vascular endothelial growth factor
- multiple sclerosis
- white matter
- blood brain barrier
- long non coding rna
- attention deficit hyperactivity disorder
- cognitive impairment
- transcranial direct current stimulation
- high frequency
- high resolution
- diabetic rats
- childhood cancer