Active Immunization Against NMDA NR1 Subunit as a Model of Autoimmune Encephalitis

Objective To identify and develop the optimal active immunization induction method for NMDAR encephalitis in rodents. Background Encephalitis is a devastating neurologic disorder with high morbidity mortality. Many cases are autoimmune. N-Methyl-D-aspartic acid receptor (NMDAR) (NMDARE), characterized by antibodies against blood spinal fluid of patients, most common form autoimmune (AE). A translational rodent model NMDARE would allow in-depth studies into AE pathophysiology, leading to advances diagnosis treatment this debilitating neuropsychiatric disorder. Design/Methods 7-week-old female C57BL/6J mice were injected subcutaneously an emulsion complete Freund's adjuvant, attenuated Mycobacterium tuberculosis (TB), 30 amino peptide flanking NR1 subunit N368/G369 residue targeted patients. Three different methods tested varying amount injection pertussis toxin, subcutaneous sites, reimmunization, amounts TB. Mice bled biweekly sacrificed at 2, 4, 6, 8, 14 weeks. Serum CSF antibody titer; mouse behavior; hippocampal protein cluster density; brain immune cell entry cytokine content examined. Results Immunized had serum antibodies. exhibited behavioral changes, altered protein, entry, elevated cytokines their brains. Titers higher changes sustained reimmunized mice. Conclusions Active portion patients resulted robust production fluid, elevations cells cytokines, Reimmunization was needed sustain responses. therefore holds potential as NMDARE, allowing creation novel generation diagnostics therapeutics.