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    Investigating the cumulative effects of Delta 9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats

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    Author
    Bhatt, D; Hazari, A; Yamakawa, GR; Salberg, S; Sgro, M; Shultz, SR; Mychasiuk, R
    Date
    2020-01-01
    Source Title
    Brain Communications
    Publisher
    OXFORD UNIV PRESS
    University of Melbourne Author/s
    Shultz, Sandy
    Affiliation
    Medicine and Radiology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Bhatt, D., Hazari, A., Yamakawa, G. R., Salberg, S., Sgro, M., Shultz, S. R. & Mychasiuk, R. (2020). Investigating the cumulative effects of Delta 9-tetrahydrocannabinol and repetitive mild traumatic brain injury on adolescent rats. BRAIN COMMUNICATIONS, 2 (1), https://doi.org/10.1093/braincomms/fcaa042.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/251745
    DOI
    10.1093/braincomms/fcaa042
    Abstract
    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.

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