Delayed cell death in the contralateral hippocampus following kainate injection into the CA3 subfield

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A model of epileptic cell death has been developed employing unilateral injections of kainic acid, a glutamate agonist, into the CA3 subfield of the hippocampus. The contralateral hippocampus, where neuronal damage is induced by hyperactivity in afferent pathways, served as the model structure. The pattern of cell death in this model was shown earlier to correspond to the vulnerable regions in human temporal lobe epilepsy. In the present time-course study we demonstrated that the different subpopulations of vulnerable cells in the contralateral hippocampus of the rat degenerate at different times following kainate injection. Spiny calretinin-containing cells in the hilus and CA3 stratum lucidum disappear at 12-24 h, other types of hilar neurons and CA3c pyramidal cells show shrinkage and argyrophilia at two days, whereas CA1 pyramidal cells degenerate at three days postinjection. The majority of cells destined to die showed a transient expression of the heatshock protein 72, approximately one day (for hilar-CA3c) or two days (for CA1) before degeneration. Parvalbumin-immunoreactivity transiently disappeared from the soma and dendrites of interneurons between the first and the fourth day. The results suggest that seizure-induced cell death is delayed, therefore acute oedema, even if it occurs, is insufficient to kill neurons. The only exception is the population of calretinin-containing interneurons degenerating at 12-24 h. The further one day delay between hilar-CA3c and CA1 cell death is likely to be due to differences in the relative density of glutamate receptor types (kainate versus NMDA) and the source of afferent input of these subfields. Thus, simple pharmacotherapy targeting only one of the excitotoxic mechanisms (i.e. acute oedema of calretinin cells versus delayed death of hilar-CA3c and CA1 cells at different time points) is likely to fail.

Original languageEnglish
Pages (from-to)847-860
Number of pages14
Issue number4
Publication statusPublished - Jun 1995


  • 3,3′-diaminobenzidine-4HCL
  • CA1, CA2, CA3
  • DAB
  • HSP
  • Hippocampal subfields according to Lorente de No
  • KA
  • N-methyl-d-aspartate
  • NGS
  • NMDA
  • NRS
  • PB
  • Phosphate buffer
  • TBS
  • Tris-buffered saline
  • heat-shock protein
  • kainic acid
  • normal goat serum
  • normal rabbit serum

ASJC Scopus subject areas

  • Neuroscience(all)

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