Microglial polarization in posttraumatic epilepsy: Potential mechanism and treatment opportunity

Peravina Therajaran, John A. Hamilton, Terence J. O'Brien, Nigel C. Jones, Idrish Ali

Research output: Contribution to journalReview ArticleResearchpeer-review

1 Citation (Scopus)

Abstract

Owing to the complexity of the pathophysiological mechanisms driving epileptogenesis following traumatic brain injury (TBI), effective preventive treatment approaches are not yet available for posttraumatic epilepsy (PTE). Neuroinflammation appears to play a critical role in the pathogenesis of the acquired epilepsies, including PTE, but despite a large preclinical literature demonstrating the ability of anti-inflammatory treatments to suppress epileptogenesis and chronic seizures, no anti-inflammatory treatment approaches have been clinically proven to date. TBI triggers robust inflammatory cascades, suggesting that they may be relevant for the pathogenesis of PTE. A major cell type involved in such cascades is the microglial cells—brain-resident immune cells that become activated after brain injury. When activated, these cells can oscillate between different phenotypes, and such polarization states are associated with the release of various pro- and anti-inflammatory mediators that may influence brain repair processes, and also differentially contribute to the development of PTE. As the molecular mechanisms and key signaling molecules associated with microglial polarization in brain are discovered, strategies are now emerging that can modulate this polarization, promoting this as a potential therapeutic strategy for PTE. In this review, we discuss the relevant literature regarding the polarization of brain-resident immune cells following TBI and attempt to put into perspective a role in epilepsy pathogenesis. Finally, we explore potential strategies that could polarize microglia/macrophages toward a neuroprotective phenotype to mitigate PTE development.

Original languageEnglish
Pages (from-to)203-215
Number of pages13
JournalEpilepsia
Volume61
Issue number2
DOIs
Publication statusPublished - Feb 2020

Keywords

  • disease modification
  • microglial polarization
  • neuroinflammation
  • posttraumatic epilepsy
  • traumatic brain injury

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