ABSTRACT
Epilepsy is one of the most common neurological conditions, which is characterized by recurrent unprovoked seizures. Drug treatment is still the main method for the disease. Although remarkable progress has been made in the development of antiepileptic drugs in recent years, there is still a poor curative effect on patients with refractory epilepsy. This review will focus on the current status and pathogenesis of epilepsy, as well as the antiepileptic drugs (targeting sodium channels, calcium channels, potassium channels, and the balance of γ-aminobuyric acid /glutamate system, respectively) that have been developed based on classical epileptogenic mechanisms. Further the antiepileptic drugs acting on new targets (epigenetic interferers, synaptic vesicle glycoprotein 2A modulators, mammalian target of rapamycin signal pathway blockers, carbonic anhydrase inhibitors, cannabidiol and adenosine inhibitors) have also been discussed.
ABSTRACT
Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4/Bcl-6 T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.