What is it about?
This study provides proof of concept that a brain malformation can simultaneously predispose to the epileptic phenotype and a severe autoimmune response against the central nervous system (CNS) and that these phenomena are causally interconnected. We show that the MAM/pilocarpine rat could serve as a preclinical tool to model brain malformations concomitant with CNS autoimmunity.
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Why is it important?
Autoimmune pathogenic mechanisms were recently proposed in some human epileptic malformation of cortical development. However, an experimental model that recapitulates both cerebral cortical malformation and brain autoimmune response has never been described so far. The availability of a preclinical model, such as the MAM/Pilocarpine rat as shown in the present paper, presenting both these pathological entities could serve to analyze the mechanisms and interdependence of brain malformations, CNS autoimmunity, and epilepsy. In addition, this study supports further investigations aimed at testing the repurposing of immunomodulatory treatments, alone or in combination with anti-seizure drugs, at least in a subset of drug-resistant epileptic patients with brain malformations. Another aspect we would like to emphasize is that in our model, CNS autoimmunity is triggered in a modality significantly different from other experimental models of CNS autoimmunity described so far.
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This page is a summary of: CNS autoimmune response in the MAM/pilocarpine rat model of epileptogenic cortical malformation, Proceedings of the National Academy of Sciences, April 2024, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2319607121.
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