Events

<p>Traumatic brain (TBI) injuries result in profound local hypoperfusion, ischemia, chronic inflammation and refractory seizures(post-traumatic epilepsy (PTE)), and restrict drug delivery to the site of impact so that peripheral treatment alone would have limited access to the site of injury during the most critical phases of neurotrauma. Cannabidiol (CBD), the major non-psychotropic cannabinoid, has anti-convulsant, anti-inflammatory, anti-nociceptive, antioxidant, and immuno-suppressive properties not fully understood. In pre-juvenile rats, microinjection of CBD attenuated kainate(KA)-induced seizures to a greater extent than intraperitoneal injection, indicating that local drug administration was more effective. In adult rats after experimental TBI, our modified CBD-infused implant applied extradural with oil injection supplementation restored vestibulomotorand cognitive functions compared to systemic treatment alone. We questioned whether the CBD or the low concentrations of THC in the extract was responsible for behavioral and cellular recovery.We hypothesized that an optimal ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) is required to protect against neuropathological consequences following TBI greater than either substance alone. Varied CBD:THC extract concentrations were compared with hempCBD lacking THC (CBD0). Neurons, glia, and parvalbumin interneurons (PV-INs) were evaluated. Weight loss was observed following high doses of THC dominant cannabis, THC100:1. Neuroscoresand vestibulomotorperformance were restored more with CBD:THC300:1-10:1. However, THC dominant treatments resulted in early onset to spontaneous seizures post-TBI. In a non-reward T-maze, the CBD10:1group had the highest alternation rates; TBI + vehicle, CBD0, CBD1:1, and THC100:1treatment groups had the lowest. The novel object recognition memory task showed CBD300:1treated animals had the best performance, while TBI or THC100:1treated groups had the worst. The forced swim test (FST) showed immobility time was highest after TBI and lowest after THC100:1treatment. The elevated plus maze (EPM) revealed the CBD0group spent the most time in closed arms. Both tests indicate that reduced anxiety was THC dependent. All combinations resulted in reduced injury but CBD10:1and THC20:1gave the most protection and THC100:1the least. Reduced anxiety level was THC dependent but higher doses were pro-convulsant cautioning THC dosing. Reduced GFAP labeling was highest with CBD dominant cannabis supporting its neuroprotective role against inflammation. Rescue of diminished bilateral PV-INs was observed within the hippocampus and medial prefrontal cortex (mPFC) with CBD dominant treatment (CBD300, CBD0) supporting their anticonvulsant effect. Loss of PV-INs with THC dominant treatment supports their proconvulsant effect. Thus, CBD and THC have different beneficial therapeutic effects indicating an optimal concentration ratio is critical for optimal neuropathological therapeutics.</p><p>Light refreshments before the seminar</p>