Furthermore, anakinra reduced the hippocampal expression of markers of activated microglia and astrogliosis in mice with autoimmune seizures. we performed behavioral tests to assess motor function, anxiety, and memory, followed by hippocampus tissue analysis to assess astrocytic (GFAP) and microglial (Iba-1) activation. == Results: == Of 31 L(+)-Rhamnose Monohydrate mice infused with purified patient NMDAR-IgG (n = 17) or monoclonal NMDAR-IgG (n = 14), 81% developed seizures. Median baseline daily seizure counts during exposure to antibodies were 3.9; most seizures were electrographic. Median duration of seizures during the baseline was 82.5 sec. Anakinra administration attenuated daily seizure frequency by 60% (p = 0.02). Anakinra reduced seizure duration; however, the effect was delayed and become apparent only after the cessation of treatment (p = 0.04). Anakinra improved novel object recognition in mice with antibody-induced seizures (p = 0.03) but did not alter other behaviors. Anakinra reduced the expression of GFAP and Iba-1 in the hippocampus of mice with seizures, indicating decreased astrocytic and microglial activation. == Significance: == Our L(+)-Rhamnose Monohydrate evidence supports a role for IL-1 in the pathogenesis of seizures in anti-NMDAR encephalitis. These data are consistent with therapeutic effects of anakinra in other severe autoimmune and inflammatory seizure syndromes. Targeting inflammation via blocking IL-1 receptor mediated-signaling may be promising for developing novel treatments for refractory autoimmune seizures. Keywords:neuroinflammation, IL-1, cytokines, anti-NMDA receptor encephalitis, autoimmune seizures, autoantibodies == 1. Introduction == Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease that manifests with acute confusion, memory loss, and severe seizures in previously healthy people.1Status epilepticus is present in 45% of patients treated in intensive care settings, and seizures that do not respond to treatment develop in two-thirds of these patients.2Seizures subside in some patients after immunotherapies aimed to remove antibodies, thereby suggesting that antibody proteins were linked to clinical symptoms. 3We recently established the antibodies pathogenic role in seizures, in that intraventricular administration of cerebrospinal fluid (CSF) from affected patients, or purified patient anti-NMDAR antibodies, or commercial antibodies directed to the N-terminal domain of GluN1, into mice was shown to precipitate seizures, thereby confirming that antibodies are directly pathogenic for seizures.4 Along with modulation of NMDAR channels possibly resulting in increased overall excitability of the seizure network in autoimmune encephalitis, the innate immune system in patients with this condition has been increasingly considered as a potential target for new anticonvulsive therapies.5-7Seizures or brain injury can trigger neurogenic inflammation.8In particular, both brief and prolonged seizures in mice rapidly induce cyclooxygenase-2 (Cox-2) in forebrain glutamatergic neurons.9-11The resulting release of prostaglandins from these neurons exacerbates ongoing inflammatory processes and may further perpetuate seizures.12,13Proinflammatory cytokines (e.g., interleukin (IL-6, IL-17A and IL-2) are persistently elevated in the CSF and serum of anti-NMDAR encephalitis patients.14Furthermore, the levels of C-X-C motif chemokine 13 (CXCL-13) are increased in the CSF of patients with anti-NMDAR encephalitis and are positively correlated with intrathecal anti-NMDAR antibody titer, suboptimal Tgfb3 response to treatment and higher rates of disease relapse.15Corticosteroids, broad spectrum anti-inflammatory agents, are the first line of therapy for anti-NMDAR encephalitis; however, only half of patients show improvement leaving the remaining patients to be approached with other limited treatment modalities.3Identifying L(+)-Rhamnose Monohydrate the role of specific inflammatory pathways in the development of autoimmune epilepsy would uncover new therapeutic targets for seizure attenuation.8 One potential target for novel anticonvulsant therapies is IL-1 receptor-mediated signaling8,11. In inflammatory states following the recruitment of the Toll-like receptor (TLR) system, microglial cells release IL-1, a potent proconvulsant.5Similarly, the sustained seizures in status epilepticus cause neuroinflammation partly via the IL-1 system, thereby promoting epileptogenesis.8,16-18Anakinra (Kineret, Swedish Orphan Biovitrum, Sobi), a recombinant and modified version of the human IL-1 receptor antagonist protein currently approved for the treatment of rheumatoid arthritis, has been regarded as a promising therapy for inflammatory epilepsies.19It has been used effectively L(+)-Rhamnose Monohydrate in a few patients with severe autoimmune seizures, both in the acute and chronic phases.20-23Anakinra is a hydrophilic protein that penetrates the blood-brain barrier and has a.