Innate immune activation and neuroinflammatory pathways in Epilepsy.

Abstract

Epilepsy is a chronic, non-communicable neurological disease that affects more than 50 million people worldwide, making it one of the most common neurological diseases globally. Epilepsy is characterized by recurrent and unprovoked interruptions in regular brain activity, called epileptic seizures. Even though the number of Anti-Epileptic Drugs (AEDs) has expanded remarkably over the past 20 years, around 30 % of patients with epilepsy remain refractory to treatment with AEDs, have progressive cognitive impairment, and may require surgical resection of the epileptic focus to ameliorate seizure recurrence. While dysregulation of inflammatory cells and molecules within neuronal tissue is accepted as a critical factor in the development of epilepsy, it remains unclear as to how dysregulated inflammation contributes to epilepsy. It is therefore imperative to identify and elucidate the neuroinflammatory pathways that may lead to the development of epilepsy and/or its progression. In this paper, the cells and molecules that contribute to neuroinflammation and epilepsy are reviewed. The role of glia (astrocytes and microglia), their sensing and initiation of neuroinflammation via pattern recognition receptors (such as TLRs and NLRs), and their downstream signaling pathways leading to cytokines and chemokines that may be regulated as therapeutic interventions are discussed. With a third of epileptic patients exhibiting drug-refractory epilepsy, we conclude with an analysis of existing anti-epileptic drugs and their effects on neuroinflammation.