Neuronal Injury, Gliosis, and Glial Proliferation in Two Models of Temporal Lobe Epilepsy

J Neuropathol Exp Neurol. 2016 Apr;75(4):366-78. doi: 10.1093/jnen/nlw008. Epub 2016 Mar 4.

Abstract

It is estimated that 30%-40% of epilepsy patients are refractory to therapy and animal models are useful for the identification of more efficacious therapeutic agents. Various well-characterized syndrome-specific models are needed to assess their relevance to human seizure disorders and their validity for testing potential therapies. The corneal kindled mouse model of temporal lobe epilepsy (TLE) allows for the rapid screening of investigational compounds, but there is a lack of information as to the specific inflammatory pathology in this model. Similarly, the Theiler murine encephalomyelitis virus (TMEV) model of TLE may prove to be useful for screening, but quantitative assessment of hippocampal pathology is also lacking. We used immunohistochemistry to characterize and quantitate acute neuronal injury and inflammatory features in dorsal CA1 and dentate gyrus regions and in the directly overlying posterior parietal cortex at 2 time points in each of these TLE models. Corneal kindled mice were observed to have astrogliosis, but not microgliosis or neuron cell death. In contrast, TMEV-injected mice had astrogliosis, microgliosis, neuron death, and astrocyte and microglial proliferation. Our results suggest that these 2 animal models might be appropriate for evaluation of distinct therapies for TLE.

Keywords: Animal models; Antiseizure drugs; Astrogliosis; Corneal kindling; Microglia; Temporal lobe epilepsy; Theiler murine encephalomyelitis virus (TMEV)..

Publication types

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

MeSH terms

  • Animals
  • Calcium-Binding Proteins / metabolism
  • Cardiovirus Infections / complications
  • Cell Proliferation / physiology*
  • Disease Models, Animal*
  • Epilepsy, Temporal Lobe / complications*
  • Epilepsy, Temporal Lobe / pathology
  • Epilepsy, Temporal Lobe / virology
  • Fluoresceins / metabolism
  • Gliosis / etiology*
  • Ki-67 Antigen / metabolism
  • Kindling, Neurologic / physiology
  • Mice
  • Mice, Inbred C57BL
  • Microfilament Proteins / metabolism
  • Microscopy, Confocal
  • Nerve Tissue Proteins / metabolism
  • Neuroglia / pathology*
  • Neurons / pathology*
  • Theilovirus / pathogenicity

Substances

  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Fluoresceins
  • Ki-67 Antigen
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • fluoro jade