Neuroprotective and anti-inflammatory effects of cannabidiol in rats submitted to severe traumatic brain injury

Abstract Traumatic brain injury (TBI) is an acute cerebral insult that affects neuronal excitability, inflammatory responses and increases susceptibility to seizures and epilepsy. Cannabidiol (CBD) shows anticonvulsant effects and has been proposed for the treatment of epilepsy. However, its neuroprotective effects after TBI have been poorly explored. In this study, the effects of CBD were investigated following TBI, considering alterations in brain cells as well as changes in seizure susceptibility induced by pentylenetetrazol (PTZ) as a second-hit. TBI was induced in rats using the lateral fluid percussion injury (LFPI) model. Twenty-four hours after TBI, both sham and TBI-rats were treated with saline or CBD (5 mg/kg) for five days. After thirty days, animals received a subconvulsive dose of PTZ (35 mg/kg), and the incidence, intensity, latency, and duration of seizures were evaluated. Brains were processed for immunohistochemistry for Iba-1 (microglial cells), GFAP (astrocyte), and parvalbumin (PV). The number of Iba-1 and GFAP cells were reduced in the cortex of the TBI-CBD group compared to TBI-SAL group, and PV cells were reduced in the cortex of TBI-SAL rats compared to Sham groups. Our study indicates that CBD has a long-lasting anti-inflammatory effect and neuroprotective potential after severe brain injury. Craniotomy procedure may influence the threshold to seizures, revealing the importance of conducting studies comparing these effects in TBI animals.