University of Worcester Worcester Research and Publications

IgG leakage may contribute to neuronal dysfunction in drug-refractory epilepsies with blood-brain barrier disruption

Michalak, Z., Lebrun, A., Di Miceli, Mathieu ORCID:, Rousset, M-C, Crespel, A., Coubes, P., Henshall, D.C., Lerner-Natoli, M. and Rigau, V. (2012) IgG leakage may contribute to neuronal dysfunction in drug-refractory epilepsies with blood-brain barrier disruption. Journal of neuropathology and experimental neurology, 71 (9). pp. 826-838. ISSN 1554-6578

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Focal epilepsies are often associated with blood-brain barrier disruption. In 4 entorhinal cortex tissue samples and 13 hippocampal samples from patients with pharmacoresistent temporal lobe epilepsy, we observed immunoglobulin G (IgG) leakage in the parenchyma and IgG-positive neurons that had evidence of neurodegeneration, such as shrinkage and eosinophilia. These findings were not present in samples from 12 nonepileptic control subjects. To complement these findings, we used a rat in vivo model that mimics the development of limbic epilepsy with blood-brain barrier disruption. During epileptogenesis, IgG leakage and neuronal IgG uptake increased concomitantly with the occurrence of seizures. Immunoglobulin G accumulation in neurons was selective, particularly for interneurons and pyramidal neurons. Immunohistochemistry and electron microscopy showed that IgG uptake in the rat neurons was associated with eosinophilia, shrinkage, and ultrastructural degenerative changes. Moreover, IgG-positive neurons lost their NeuN immunohistochemical staining. Together, these observations suggest that IgG leakage is related to neuronal impairment and may be a pathogenic mechanism in epileptogenesis and chronic epilepsy.

Item Type: Article
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Uncontrolled Discrete Keywords: blood-brain barrier, immunoglobulin G, NeuN, neuroregeneration, pilocarpine model, temporal lobe epilepsy
Divisions: College of Health, Life and Environmental Sciences > School of Science and the Environment
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Depositing User: Mathieu Di Miceli
Date Deposited: 06 Oct 2021 11:17
Last Modified: 07 Dec 2021 16:54

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