Astrocytes and epilepsy

Neurotherapeutics. 2010 Oct;7(4):424-38. doi: 10.1016/j.nurt.2010.08.002.

Abstract

Astrocytes form a significant constituent of seizure foci in the human brain. For a long time it was believed that astrocytes play a significant role in the causation of seizures. With the increase in our understanding of the unique biology of these cells, their precise role in seizure foci is receiving renewed attention. This article reviews the information now available on the role of astrocytes in the hippocampal seizure focus in patients with temporal lobe epilepsy with hippocampal sclerosis. Our intent is to try to integrate the available data. Astrocytes at seizure foci seem to not be a homogeneous population of cells, and in addition to typical glial fibrillary acidic protein, positive reactive astrocytes also include a population of neuron glia-2-like cells The astrocytes in sclerotic hippocampi differ from those in nonsclerotic hippocampi in their membrane physiology, having elevated Na+ channels and reduced inwardly rectifying potassium ion channels, and some having the capacity to generate action potentials. They also have reduced glutamine synthetase and increased glutamate dehydrogenase activity. The molecular interface between the astrocyte and microvasculature is also changed. The astrocytes are also associated with increased expression of many molecules normally concerned with immune and inflammatory functions. A speculative mechanism postulates that neuron glia-2-like cells may be involved in creating a high glutamate environment, whereas the function of more typical reactive astrocytes contribute to maintain high extracellular K+ levels; both factors contributing to the hyperexcitability of subicular neurons to generate epileptiform activity. The functions of the astrocyte vascular interface may be more critical to the processes involved in epileptogenesis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Astrocytes / classification
  • Astrocytes / pathology*
  • Astrocytes / physiology*
  • Astrocytes / ultrastructure
  • Brain / metabolism
  • Brain / pathology*
  • Calcium / metabolism
  • Epilepsy / metabolism
  • Epilepsy / pathology*
  • Epilepsy / physiopathology
  • Gene Expression / physiology
  • Glial Fibrillary Acidic Protein
  • Glutamic Acid / metabolism
  • Humans
  • Models, Biological

Substances

  • Glial Fibrillary Acidic Protein
  • Glutamic Acid
  • Calcium