4.7 Review

The Neuroinflammatory Role of Pericytes in Epilepsy

Journal

BIOMEDICINES
Volume 9, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9070759

Keywords

pericytes; mural cells; cytokine; blood-brain barrier; neuroinflammation

Funding

  1. Kawano Masanori Memorial Foundation for Promotion of Pediatrics in Japan [30-7]
  2. Japan Epilepsy Research Foundation [20012]
  3. Japan Epilepsy Research Foundation

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Pericytes are crucial for maintaining the integrity of the blood-brain barrier and have been implicated in neuroinflammation associated with epilepsy. Clinical and experimental studies have shown that pericytes undergo morphological changes and redistribution in response to proinflammatory cytokines, potentially contributing to epilepsy pathogenesis and BBB permeability. Furthermore, pericytes may act as sensors of the inflammatory response and have potential as a therapeutic target for seizure disorders.
Pericytes are a component of the blood-brain barrier (BBB) neurovascular unit, in which they play a crucial role in BBB integrity and are also implicated in neuroinflammation. The association between pericytes, BBB dysfunction, and the pathophysiology of epilepsy has been investigated, and links between epilepsy and pericytes have been identified. Here, we review current knowledge about the role of pericytes in epilepsy. Clinical evidence has shown an accumulation of pericytes with altered morphology in the cerebral vascular territories of patients with intractable epilepsy. In vitro, proinflammatory cytokines, including IL-1 beta, TNF alpha, and IL-6, cause morphological changes in human-derived pericytes, where IL-6 leads to cell damage. Experimental studies using epileptic animal models have shown that cerebrovascular pericytes undergo redistribution and remodeling, potentially contributing to BBB permeability. These series of pericyte-related modifications are promoted by proinflammatory cytokines, of which the most pronounced alterations are caused by IL-1 beta, a cytokine involved in the pathogenesis of epilepsy. Furthermore, the pericyte-glial scarring process in leaky capillaries was detected in the hippocampus during seizure progression. In addition, pericytes respond more sensitively to proinflammatory cytokines than microglia and can also activate microglia. Thus, pericytes may function as sensors of the inflammatory response. Finally, both in vitro and in vivo studies have highlighted the potential of pericytes as a therapeutic target for seizure disorders.

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