Effects of GABAergic Agents on Multiple Sclerosis. A Narrative Review of In-vivo Models

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 for MS patients alleviating their symptoms and providing better quality years. Objective 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. Methods 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. 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 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.

Automated summary

This review focuses on the potential benefits of GABA agonists and modulators in the treatment of multiple sclerosis (MS) using an in vivo model of experimental autoimmune encephalomyelitis (EAE). The results showed that these drugs can regulate the immune response, reduce inflammation, protect nerve fibers, and improve clinical symptoms. Therefore, GABA agonists and modulators may be suitable therapeutic candidates for the treatment of MS.