Inhibitory role of diazepam on autoimmune inflammation in rats with experimental autoimmune encephalomyelitis

Diazepam Inhibits Proliferation of Lymph Node Cells Isolated from Rats with Experimental Autoimmune Encephalomyelitis

“…Previous results demonstrated that the treatment of rats with 0.1 mg/kg/day diazepam during the inductive phase of EAE (6-11 dpi) reduces the incidence and clinical signs in animals challenged with the disease [13]. In treated animals, we also observed a reduction in some immunological parameters, such as DTH reaction, antibody production and proliferation induced by MBP in MNC isolated from popliteal lymph nodes.…”

“…CD25 levels markedly increase in cells cultured in the presence of Con A for 24 h. Incubation with Con A and diazepam reduced CD25 levels, but only in CD8+ T cells, with no effect on the CD4+ T cell population. This may explain our observation in vivo when analyzing DTH responses in diazepam-treated animals compared to vehicle-injected animals [13]. On days 9 and 12, diazepam-treated animals showed less thickness associated to swelling 24 h after the injection of MBP in the corresponding ear.…”

“…A recent work shows that acute and long-term diazepam treatment decreased the number of apoptotic cells, increased the percentage of T-cytotoxic cells and decreased the percentage of B cells, and increased corticosterone serum levels [12]. In this respect, we described that administration of low doses (0.1 mg/kg/day) of diazepam after active induction of experimental autoimmune encephalomyelitis (EAE) led to a marked decrease in the incidence and clinical signs of the disease, and diminished delayed-type hypersensitivity (DTH) responses, proliferation following stimulation with the encephalitogenic myelin basic protein (MBP), anti-MBP antibody production and spinal cord histological lesions associated with the disease [13]. Interestingly, alprazolam, another benzodiazepine derivative, also decreased the severity of clinical, histological and neuroendocrine manifestations of EAE in Lewis rats but only when the animals were exposed to stressful conditions [14].…”

“…These results indicate that both glutamatergic and GABAergic neurotransmission is impaired in symptomatic EAE animals, and could contribute to clinical symptoms and disease progression. Treatment with diazepam inhibited this reduction in glutamate release in frontal cortex synaptosomes from EAE animals [13]. However, the modulatory effect of benzodiazepines on T cells is limited and the underlying mechanism is poorly defined.…”

Peripherally derived T regulatory and γδ T cells have opposing roles in the pathogenesis of intractable pediatric epilepsy

“…Recent evidence suggests a link between neuroinflammation and epileptogenesis ( Fabene et al, 2008 ; Vezzani et al, 2011 ; Xu et al, 2013 ). Several commonly prescribed anticonvulsants have antiinflammatory effects ( Goto et al, 2003 ; Bibolini et al, 2011 ; Chuang et al, 2014 ). Additionally, corticosteroids have shown promising results in refractory epilepsy cases and in select epilepsy syndromes ( Chutorian et al, 1968 ; Gayatri et al, 2007 ; Grosso et al, 2008 ; Xu et al, 2013 ).…”