The Egyptian Journal of Neurology, Psychiatry and Neurosurgery (Jun 2024)

Astrocyte dysregulation as an epileptogenic factor: a systematic review

  • Komang Trisna Sumadewi,
  • Bryan Gervais de Liyis,
  • Ni Made Linawati,
  • I Putu Eka Widyadharma,
  • I Nyoman Mantik Astawa

DOI
https://doi.org/10.1186/s41983-024-00843-7
Journal volume & issue
Vol. 60, no. 1
pp. 1 – 20

Abstract

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Abstract Background Epilepsy initiation involves multifactorial etiologies, including genetic susceptibility, structural anomalies, and glial cell dysregulations, particularly in astrocytes. Despite advancements in understanding various factors, the mechanisms of astrocyte dysregulation in epilepsy, critical for neural homeostasis, remain elusive, requiring comprehensive evaluation of molecular pathways and cellular interactions for future targeted interventions. Methods A systematic search of PubMed, ScienceDirect, and the Cochrane databases up to January 1st 2024 identified relevant studies predominantly from experimental models, forming the basis for an in-depth analysis of astrocytic contributions to epileptic pathophysiology. The aims, subjects, epilepsy induction techniques, assessment methods, and findings of each studies were presented. Results A total of 24 clinical trials met the inclusion criteria and were included in the systematic review. Altered potassium buffering compromises extracellular potassium regulation, fostering hyperexcitability. Aquaporin dysfunction disrupts water homeostasis, aggravating seizure susceptibility. Disturbances in glutamatergic transmission, marked by changes in glutamate transporter function, contribute to excitotoxicity, fueling epileptogenesis. Intricacies in calcium signaling and disruptions in calcium-binding proteins tip intracellular calcium balance towards hyperexcitability. Dysfunctional GABA transporters compromise inhibitory neurotransmission, upsetting excitatory–inhibitory balance. Gap junction protein dysregulation disrupts astroglial networks, impacting neuronal synchronization in epileptogenic circuitry. Compromised BBB allows entry of epileptogenic factors, exacerbating the epileptogenic milieu. Conclusions Collectively, these astrocytic dysregulations unveil intricate contributors to epilepsy onset and progression.

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