Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisboa, Portugal.
Int J Mol Sci. 2020 Oct 3;21(19):7309. doi: 10.3390/ijms21197309.
Epilepsy is one of the most common brain diseases worldwide, having a huge burden in society. The main hallmark of epilepsy is the occurrence of spontaneous recurrent seizures, having a tremendous impact on the lives of the patients and of their relatives. Currently, the therapeutic strategies are mostly based on the use of antiepileptic drugs, and because several types of epilepsies are of unknown origin, a high percentage of patients are resistant to the available pharmacotherapy, continuing to experience seizures overtime. Therefore, the search for new drugs and therapeutic targets is highly important. One key aspect to be targeted is the aberrant adult hippocampal neurogenesis (AHN) derived from Neural Stem Cells (NSCs). Indeed, targeting seizure-induced AHN may reduce recurrent seizures and shed some light on the mechanisms of disease. The endocannabinoid system is a known modulator of AHN, and due to the known endogenous antiepileptic properties, it is an interesting candidate for the generation of new antiepileptic drugs. However, further studies and clinical trials are required to investigate the putative mechanisms by which cannabinoids can be used to treat epilepsy. In this manuscript, we will review how cannabinoid-induced modulation of NSCs may promote neural plasticity and whether these drugs can be used as putative antiepileptic treatment.
癫痫是全球最常见的脑部疾病之一，给社会带来了巨大的负担。癫痫的主要特征是自发性反复发作，这对患者及其亲属的生活产生了巨大影响。目前，治疗策略主要基于抗癫痫药物的使用，但由于多种类型的癫痫病因不明，相当一部分患者对现有药物治疗产生耐药性，随着时间的推移仍会出现癫痫发作。因此，寻找新的药物和治疗靶点非常重要。一个需要关注的关键方面是源自神经干细胞的异常成年海马神经发生（AHN）。事实上，针对癫痫发作引起的 AHN 可能会减少反复发作，并为疾病机制提供一些启示。内源性大麻素系统是 AHN 的已知调节剂，由于其具有已知的内源性抗癫痫特性，它是生成新型抗癫痫药物的一个有趣候选者。然而，需要进一步的研究和临床试验来探究大麻素治疗癫痫的潜在机制。在本文中，我们将综述大麻素诱导的神经干细胞调节如何促进神经可塑性，以及这些药物是否可用于潜在的抗癫痫治疗。
