Microglia–Neuron Communication in Epilepsy

Abstract

Epilepsy has remained a significant social concern and financial burden globally. Current therapeutic strategies are based primarily on neurocentric mechanisms that have not proven successful in at least a third of patients, raising the need for novel alternative and complementary approaches. Recent evidence implicates glial cells and neuroinflammation in pathogenesis of epilepsy with the promise of targeting these cells to complement existing strategies. Specifically, microglial involvement, as a major inflammatory cell in the epileptic brain, has been poorly studied. In this review, we highlight microglial reaction to experimental seizures, discuss microglial control of neuronal activities, and propose the functions of microglia during acute epileptic phenotypes, delayed neurodegeneration and aberrant neurogenesis. Future research that would help fill in the current gaps in our knowledge including epilepsy-induced alterations in basic microglial functions, neuro-microglial interactions during chronic epilepsy, and microglial contributions to developmental seizures. Studying the role of microglia in epilepsy could inform therapies to better alleviate the disease.

Coupled Oscillators Model of Hyperexcitable Neuroglial Networks

“…Whether microglia are helpful or harmful in pathological conditions remains unclear, and both neuroprotective and neurodegenerative roles in epilepsy have been identified [66] [69]. This was also observed in the model, as the effect of the microglial pruning mechanism was not the same under different conditions.…”

“…The larger the coupling coefficient, the stronger the connection between the microglia and the neurons, and the more effective the pruning will be. Following seizures, there was evidence of a) increased numbers of microglia, and b) increased fractalkine signaling between the microglia and the neurons [69]. This suggests stronger association between microglia and neurons in epilepsy, and warrants a high coupling value in the network model under hyperexcitable conditions.…”

“…Furthermore, they are important in processes required for learning, memory, and cognitive function [68]. During development, they are known to play a role in regulating neurogenesis, in promoting neural precursor cell development, and in enhancing neuronal survival [69] [70]. In the mature CNS, microglia can regulate long term potentiation (LTP), synaptic scaling, and basal glutamergic and GABAergic transmission [71] [72] [73].…”

“…Wake In epilepsy, microglia undergo reactive gliosis, a component of neuroinflammation involving structural and metabolic changes. Following seizures, changes in the morphological characteristics of microglia, such as increased numbers, increased cell body size, fewer processes, and decreased process branching have been reported [69]. In addition, increased expression of certain proteins, such as fractalkine receptors, have been observed in epileptic patients [79].…”

“…There is evidence that they are neuroprotective early in acute seizures [69]. Eyo et al reported increased microglial contact with neuronal elements that when blocked resulted in a worsened seizure phenotype [81].…”