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.

Potent P2Y12 inhibitors versus clopidogrel to predict adherence to antiplatelet therapy after an acute coronary syndrome: insights from IDEAL-LDL.

BACKGROUND: Superiority of potent P2Y12 inhibitors over clopidogrel after an acute coronary syndrome (ACS) has been well established, however potent P2Y12 inhibition is responsible for more adverse events, which may influence patient adherence to treatment. Aim of the present study is to investigate the adherence to the prescribed P2Y12 inhibitor (P2Y12i) in patients on dual antiplatelet therapy (DAPT) after an ACS. METHODS: In an IDEAL-LDL trial substudy, we included 344 patients after ACS discharged on DAPT. The primary outcome was the difference between potent P2Y12i and clopidogrel in terms of adherence, as well as other predictors of adherence to the antiplatelet regimen. Secondary outcomes included the prevalence of DAPT continuation and its predictors and the antiplatelet regimen selection after DAPT. RESULTS: Adherence to the potent P2Y12i and to clopidogrel was observed in 140/178 (78.7%) and 111/166 (66.9%) patients (p = 0.016), respectively. In the multivariate model, after adjustment for P2Y12i switching during the first year of therapy, there was no difference observed in adherence between potent P2Y12i and clopidogrel (odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.55-1.74). Significant predictors included history of cardiovascular disease (CVD) (OR = 0.51, 95% CI = 0.31-0.86) and percutaneous coronary intervention (PCI) index event treatment (OR = 2.58, 95% CI = 1.38-4.82). Of patients, 72% continued DAPT >12 months and female gender was a negative predictor of DAPT prolongation (adjusted OR = 0.43, 95% CI = 0.21-0.90). DAPT was continued until the end of follow-up in 42.7%, while 54.6% resumed with single antiplatelet regimen. CONCLUSIONS: Adherence to DAPT was not affected by the P2Y12i potency, whereas history of CVD and PCI treatment were associated with reduced and increased adherence, respectively. CLINICAL TRIAL REGISTRATION: NCT02927808, https://clinicaltrials.gov/ct2/show/NCT02927808.

Predictive Role of Platelet-Associated Indices on Admission and Discharge in the Long-Term Prognosis of Acute Coronary Syndrome Patients.

Our study aimed to investigate the association between platelet indices and their in-hospital change and long-term prognosis in acute coronary syndrome (ACS). Data from a randomized controlled trial (NCT02927808) recruiting ACS patients were analyzed (survival analysis). The examined variables were platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) on admission and discharge, as well as their alteration during hospitalization. The primary endpoint was major adverse cardiac events (MACE) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke or hospitalization for unstable angina) and all-cause mortality, while secondary endpoints were all-cause hospitalization and bleeding events. The study included 252 patients with a follow-up of 39 (28-45) months. In the univariate analysis, MACE was associated with discharge PC [hazard ratio (HR) 2.20, 95% confidence interval (CI) 1.10-4.40], discharge MPV (HR 0.48, 95% CI 0.25-0.94), and in-hospital PC difference (HR 0.25, 95% CI 0.13-0.51). In the multivariable analysis, only in-hospital PC decrease correlated with lower MACE incidence (adjusted HR .27, 95% CI 0.14-0.54) and lower all-cause hospitalization risk (adjusted HR 0.36, 95% CI 0.19-0.68). PC reduction during hospitalization for ACS is an independent predictor of better prognosis.