背景:多发性硬化症(MS)是一种终生恶化的疾病,其特征是多种异质性症状。作为中枢神经系统的自身免疫性疾病,主要影响神经的髓鞘通常会导致神经症状。GABA对免疫细胞有许多影响,改变细胞因子的产生,细胞迁移和增殖。免疫细胞表达GABA受体,使GABA成为炎症调节剂。因此,GABA能相关药物可以为MS患者提供兼容的附加疗法,减轻其症状并提供更好的质量年。
目的:这篇综述的目的是强调并提供证据证明MS患者的二级治疗方案的潜在益处。旨在更好地管理这种疾病。
方法:我们通过PubMed进行了文献检索,Scopus和谷歌学者的GABA激动剂,用于实验性自身免疫性脑脊髓炎(EAE)体内模型的拮抗剂和调节剂,考虑到某些纳入和排除标准。
结果:对GABA-a和GABA-b激动剂和调节剂的体内研究显示EAE小鼠中自身免疫应答的调节。还证明了中枢神经系统中髓鞘敏感纤维的保存增加和轴突损伤减少。Further,减少单核炎症浸润,还报道了促炎细胞因子减少和活性氧(ROS)水平降低。生物学结果包括疾病峰值严重程度降低,持续时间,治疗组的临床评分和EAE发生率。
结论:在EAE的体内模型中,GABA激动剂和调节剂在挑战疾病病理生理学的不同方面是有效的。研究表明,通过调节EAE大鼠的自身免疫反应进行神经保护具有显着相关性,这表明它们应被视为临床使用的适当治疗候选药物,同时进一步的临床研究也可以使其在临床实践中的给药能力增强。
Multiple sclerosis (MS) is a lifelong deteriorating disease characterized by multiple heterogeneous symptoms. Being an autoimmune disease of the central nervous system, mainly affecting the myelin sheath of the nerves ordinarily results in neurological symptoms. GABA has numerous effects on the immune cells, altering cytokine production, cell migration and proliferation. Immune cells express GABA receptors making GABA an inflammation modulator. Therefore, GABAergic- associated agents could provide a compatible add-on therapy for MS patients alleviating their symptoms and providing better quality years.
This review aims to highlight and provide evidence of the potential benefits of a secondary treatment option in MS patients, aiming to better manage this disease.
We conducted a literature search through PubMed, Scopus and Google Scholar for GABA agonists, antagonists and modulators used in the in vivo model of experimental autoimmune encephalomyelitis (EAE), taking into consideration certain inclusion and exclusion criteria.
In vivo studies for GABA-a and GABA-b agonists and modulators showed regulation of the autoimmune response in EAE mice. Increased preservation of myelinated sensitive fibers and diminished axonal damage in the CNS was also demonstrated. Further, decreased mononuclear inflammatory infiltration, pro-inflammatory cytokines reduction and reduced levels of Reactive oxygen species (ROS) were also reported. Biological results included decreased peak disease severity, duration, clinical scores and EAE incidence in the treatment groups.
GABA agonists and modulators efficiently challenged different aspects of disease pathophysiology in vivo models of EAE. The studies showed a significant relevance of neuroprotection via modulation of the autoimmune response in EAE rats, indicating that they should be considered proper therapeutic candidates for clinical use, while also further clinical studies could empower their administration in clinical practice.