Protective Effects of Cannabidiol against Seizures and Neuronal Death in a Rat Model of Mesial Temporal Lobe Epilepsy.

Raquel A Do Val-Da Silva,Bruno S De Martinis,Ludmyla Kandratavicius,Jose E Peixoto-Santos,Jana B De Ross,Antonio W Zuardi,Renata C Scandiuzzi,Jaime E C Hallak,Marcela N R Alves,Jose A Crippa,Joao P Leite,Ingrid Esteves

doi:10.3389/fphar.2017.00131

Abstract

The present study reports the behavioral, electrophysiological, and neuropathological effects of cannabidiol (CBD), a major non-psychotropic constituent of Cannabis sativa, in the intrahippocampal pilocarpine-induced status epilepticus (SE) rat model. CBD was administered before pilocarpine-induced SE (group SE+CBDp) or before and after SE (group SE+CBDt), and compared to rats submitted only to SE (SE group), CBD, or vehicle (VH group). Groups were evaluated during SE (behavioral and electrophysiological analysis), as well as at days one and three post-SE (exploratory activity, electrophysiological analysis, neuron density, and neuron degeneration). Compared to SE group, SE+CBD groups (SE+CBDp and SE+CBDt) had increased SE latency, diminished SE severity, increased contralateral afterdischarge latency and decreased relative powers in delta (0.5–4 Hz) and theta (4–10 Hz) bands. Only SE+CBDp had increased vertical exploratory activity 1-day post SE and decreased contralateral relative power in delta 3 days after SE, when compared to SE group. SE+CBD groups also showed decreased neurodegeneration in the hilus and CA3, and higher neuron density in granule cell layer, hilus, CA3, and CA1, when compared to SE group. Our findings demonstrate anticonvulsant and neuroprotective effects of CBD preventive treatment in the intrahippocampal pilocarpine epilepsy model, either as single or multiple administrations, reinforcing the potential role of CBD in the treatment of epileptic disorders.

Highlights

Epilepsy is a disease characterized by spontaneous, recurrent seizures and the neurobiological, cognitive, behavioral, psychological, and social changes associated with the seizures (Fisher et al, 2014)
A higher number of status epilepticus (SE)+CBD rats did not developed SE when compared to SE group (35.1% vs. 15.9%; χ2, p = 0.025)
None of the SE+CBD rats presented Racine 5 seizures or died, whereas 36.1% of rats from SE group had Racine 5 seizures and one rat died during SE

Summary

Introduction

Epilepsy is a disease characterized by spontaneous, recurrent seizures and the neurobiological, cognitive, behavioral, psychological, and social changes associated with the seizures (Fisher et al, 2014). Besides its direct effects on neurotransmission, studies in several animal models and human patients have indicated anti-inflammatory, antioxidant, anxiolytic, and neuroprotective action of CBD in the central nervous system (Hampson et al, 1998; Braida et al, 2003; Campos and Guimaraes, 2008; Jones et al, 2012). After the initial animal observations, double-blind clinical studies showed anticonvulsant effects of CBD, with reduction of seizure frequency in patients with drug-resistant epilepsy (Cunha et al, 1980; Trembly and Sherman, 1990). CBD use as an add-on to conventional antiepileptic drug regimen was shown to reduce seizure frequency in severe drug-resistant epilepsies (Devinsky et al, 2016)

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Discussion

Conclusion