ABSTRACT
Objective: Systematically review evidence on using GLP-1RAs for reducing BEB in BED and BN. Methods: Comprehensive literature search (PubMed and Google Scholar) conducted for studies evaluating GLP-1Ras for BEB. Extracted data on study characteristics, efficacy, and safety. Results: Studies show that GLP-1RAs (liraglutide and dulaglutide) reduce BE frequency and comorbidities in addition to favorable psychiatric side effect profile compared to current options. However, large-scale, blinded placebo-controlled trials are lacking. Conclusion: Early findings suggest promising effects of GLP-1RAs on BEB. However, rigorous clinical trials are needed to firmly establish efficacy, dosing, safety, and comparative effectiveness before considering GLP-1RAs a viable novel approach.
ABSTRACT
The effects of non-convulsive status epilepticus (NCSE) on the developing brain remain largely elusive. Here we investigated potential hippocampal injury and learning deficits following one or two episodes of NCSE in periadolescent rats. Non-convulsive status epilepticus was induced with subconvulsive doses of intrahippocampal kainic acid (KA) under continuous EEG monitoring in postnatal day 43 (P43) rats. The RKA group (repeated KA) received intrahippocampal KA at P43 and P44, the SKA group (single KA injection) received KA at P43 and an intrahippocampal saline injection at P44. Controls were sham-treated with saline. The modified two-way active avoidance (MAAV) test was conducted between P45 and P52 to assess learning of context-cued and tone-signaled electrical foot-shock avoidance. Histological analyses were performed at P52 to assess hippocampal neuronal densities, as well as potential reactive astrocytosis and synaptic dysfunction with GFAP (glial fibrillary acidic protein) and synaptophysin (Syp) staining, respectively. Kainic acid injections resulted in electroclinical seizures characterized by behavioral arrest, oromotor automatisms and salivation, without tonic-clonic activity. Compared to controls, both the SKA and RKA groups had lower rates of tone-signaled shock avoidance (pâ¯<â¯0.05). In contextual testing, SKA rats were comparable to controls (pâ¯>â¯0.05), but the RKA group had learning deficits (pâ¯<â¯0.05). Hippocampal neuronal densities were comparable in all groups. Compared to controls, both the SKA and RKA groups had higher hippocampal GFAP levels (pâ¯<â¯0.05). The RKA group also had lower hippocampal Syp levels compared to the SKA and control groups (pâ¯<â¯0.05), which were comparable (pâ¯>â¯0.05). We show that hippocampal NCSE in periadolescent rats results in a seizure burden-dependent hippocampal injury accompanied by cognitive deficits. Our data suggest that the diagnosis and treatment of NCSE should be prompt.
