We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Evaluation of epileptogenic and behavioral features in a rat model of anti-NMDA receptor encephalitis.
- Authors
Pişkin, Şura Akat; Yüceer, Hande; Ulusoy, Canan Aysel; Küçükali, Cem İsmail; Onat, Filiz; Tüzün, Erdem; Yılmaz, Nihan Çarçak
- Abstract
Objective: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis manifests with cognitive decline, abnormal motor movements, and seizures that can be resistant to anti-seizure medications. The pathophysiological mechanisms responsible for the development of these findings have not been established. Here, we aimed to evaluate epileptogenesis and behavioral disorders in in-vivo model based on intacerebroventricular transfer of patient-derived NMDAR-positive immunoglobulins (IgGs) collected from the blood serum to non-epileptic Wistar rats. Methods: Total IgG (2 mg/ml) from NMDAR-antibody positive patients and control serum obtained from healthy subjects were administered into the lateral ventricle of adult rats in a volume of 5 μl for 11 days. Animals were examined for spontaneous epileptic seizure development by continuous electroencephalography recordings. Besides, Y-Maze, Open-field and Rota-Rod behavioral tests were applied before and after antibody administration. At the end of the behavioral tests, pentylenetetrazole (PTZ) was administered at a convulsive dose (45 mg/kg) in order to detect changes in seizure threshold and seizures were staged with the Racine scale. At the end changes in NMDAR expression in the hippocampus were evaluated immunohistochemically. Results: No spontaneous seizure was observed in animals during NMDAR-antibody infusions. However, PTZ-induced acute seizure stage, motor seizure latency, motor seizure duration and myoclonus latency were higher in the NMDAR-antibody group compared to the control (p<0.05). The horizontal and vertical activity in the open field test, as well as the percentage of spontaneous alternation and the total number of entries in the Y-maze were significantly reduced by NMDAR-antibody application (p<0.05). Human IgG staining pattern was detected in the hippocampal sections obtained from the NMDAR-antibody group, and decreased NMDAR expression is noteworthy. Conclusion: Our findings indicates patient-derived autoantibodies transferred to experimental animals may lower seizure threshold as well as impair motor performance and memory functions in anti-NMDAR encephalitis and offer potential invivo model for testing novel therapies for refractory autoimmune seizures.
- Subjects
ANTI-NMDA receptor encephalitis; AUTOANTIBODIES; IMMUNOGLOBULINS; METHYL aspartate receptors; BEHAVIORAL assessment; EPILEPSY; ANIMAL disease models; LABORATORY rats
- Publication
Anatomy: International Journal of Experimental & Clinical Anatomy, 2022, Vol 16, p232
- ISSN
1307-8798
- Publication type
Article
- DOI
10.2399/ana.22.003s