Abstract
Epilepsy is one of the most common neurological conditions. Yearly, five million people are diagnosed with epileptic-related disorders. The neuroprotective and therapeutic effect of (endo)cannabinoid compounds has been extensively investigated in several models of epilepsy. Therefore, the study of specific cell-type-dependent mechanisms underlying cannabinoid effects is crucial to understanding epileptic disorders. It is estimated that about 100 billion neurons and a roughly equal number of glial cells co-exist in the human brain. The glial population is in charge of neuronal viability, and therefore, their participation in brain pathophysiology is crucial. Furthermore, glial malfunctioning occurs in a wide range of neurological disorders. However, little is known about the impact of the endocannabinoid system (ECS) regulation over glial cells, even less in pathological conditions such as epilepsy. In this review, we aim to compile the existing knowledge on the role of the ECS in different cell types, with a particular emphasis on glial cells and their impact on epilepsy. Thus, we propose that glial cells could be a novel target for cannabinoid agents for treating the etiology of epilepsy and managing seizure-like disorders.
Highlights
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CB1R is deeply investigated in the treatment of epilepsy, and other receptors that interact with endogenous or exogenous cannabinoids have been postulated as potential targets in the control of seizures
Different approaches have attempted to prevent seizures and to control them. These treatments, some obtained from pre-clinical studies, ranging from pharmacological therapies based on new compounds such as resveratrol or vitamin E [22,23]; cell therapies rooted on stem cells, interneuron precursor transplants [24,25,26] or reprograming reactive glia into interneurons [27], and gene therapies such as neuropeptide Y transfection [28,29] to clinical studies in humans, such as modern surgery with laser-induced thermal therapy (LITT); magnetic resonance-guided LITT (MRgLITT) [30,31]; brain stimulation [32,33], or even controlling seizures with diet such as a ketogenic diet or other regimens [34]
Summary
Epilepsy is a prevalent disease in our society, being one of the most common neurological conditions affecting 1–3% of people worldwide [1]. The development of epilepsy involves a variety of molecular modifications leading to aberrant synaptic reorganization Such changes result in abnormal synchronized neuronal firing and uncontrolled excitability. These events produce spontaneous recurrent episodes of symptoms, known as seizures, which entail excitotoxicity and cell death [3,4]. Clinical and experimental research points out that those persistent levels of cytokines in the brain can act as facilitators of cell death. These molecules could decrease seizure susceptibility or even augment neuronal excitability during the progression of the disease [10,11,12]. Studying the molecular mechanisms triggered by cannabinoid action could bring novel insights into the understanding of epileptic disorders and related pathophysiological processes
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