Abstract
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-1β, TNFα, 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-1β, 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.
Highlights
Published: 30 June 2021Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction [1–6]
Whether the peripheral monocytes or the resident microglia are the primary triggers of epilepsy, as well as the extent to which the infiltrated cells are significant, remains to be determined; the combination of the roles of the pericytes in maintaining the blood–brain barrier (BBB) integrity, producing inflammatory mediators, and recruiting leukocytes indicate that the pericytes could be intimately involved in the pathogenesis of epilepsy
The roles of pericytes in maintaining BBB integrity, producing inflammatory secretions, and recruiting leukocytes highlights the potential role of pericytes in the pathogenesis of epilepsy
Summary
Accumulating evidence has demonstrated that the pathogenesis of epilepsy is linked to neuroinflammation and cerebrovascular dysfunction [1–6]. Pericyte degeneration and/or dysfunction contribute to the loss of BBB integrity, which is an early hallmark of several neurodegenerative and inflammatory conditions [8,15,16]. Another notable feature of pericytes is their ability to regulate the migration of leukocytes across the brain microvascular endothelial cell (BMVEC) barrier, which secretes key molecules that support the Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Pericytes may contribute to the mechanisms, while emerging research is investigating the extent of peripheral immune cell involvement in the inflammatory pathology of epilepsy. Given the paucity of knowledge on pericyte function in seizures and epilepsy-related pathologies, further studies are warranted to investigate pericytes as a potential therapeutic target for epilepsy treatment
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