Neuroinflammation in epileptogenesis: Insights and translational perspectives from new models of epilepsy

Melissa L. Barker-Haliski, Wolfgang Löscher, H. Steve White, Aristea S. Galanopoulou

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Animal models have provided a wealth of information on mechanisms of epileptogenesis and comorbidogenesis, and have significantly advanced our ability to investigate the potential of new therapies. Processes implicating brain inflammation have been increasingly observed in epilepsy research. Herein we discuss the progress on animal models of epilepsy and comorbidities that inform us on the potential role of inflammation in epileptogenesis and comorbidity pathogenesis in rodent models of West syndrome and the Theiler's murine encephalomyelitis virus (TMEV) mouse model of viral encephalitis–induced epilepsy. Rat models of infantile spasms were generated in rat pups after right intracerebral injections of proinflammatory compounds (lipopolysaccharides with or without doxorubicin, or cytokines) and were longitudinally monitored for epileptic spasms and neurodevelopmental and cognitive deficits. Anti-inflammatory treatments were tested after the onset of spasms. The TMEV mouse model was induced with intracerebral administration of TMEV and prospective monitoring for handling-induced seizures or seizure susceptibility, as well as long-term evaluations of behavioral comorbidities of epilepsy. Inflammatory processes are evident in both models and are implicated in the pathogenesis of the observed seizures and comorbidities. A common feature of these models, based on the data so far available, is their pharmacoresistant profile. The presented data support the role of inflammatory pathways in epileptogenesis and comorbidities in two distinct epilepsy models. Pharmacoresistance is a common feature of both inflammation-based models. Utilization of these models may facilitate the identification of age-specific, syndrome- or etiology-specific therapies for the epilepsies and attendant comorbidities, including the drug-resistant forms.

Original languageEnglish (US)
Pages (from-to)39-47
Number of pages9
JournalEpilepsia
Volume58
DOIs
StatePublished - Jul 2017
Externally publishedYes

Keywords

  • Comorbidities
  • Cytokines
  • Encephalitis
  • Epilepsy
  • Infantile spasms
  • Infection
  • Therapies
  • Viral infection

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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