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Background: 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 on MS patients alleviating their symptoms and providing better quality years. Objective: The aim of this review is to highlight and provide evidence of the potential benefits for a secondary treatment option in MS patients, aiming in better management of this disease. Methods: We conducted a literature search through PubMed, Scopus and Google Scholar for GABA agonists, antagonists and modulators used on the in vivo model of experimental autoimmune encephalomyelitis (EAE), taking into consideration certain inclusion and exclusion criteria. Results: 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. Conclusion: GABA agonists and modulators were efficient in challenging different aspects of disease pathophysiology in 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. |
