Brain Structure and Function

, Volume 220, Issue 4, pp 2423–2439 | Cite as

Widespread activation of microglial cells in the hippocampus of chronic epileptic rats correlates only partially with neurodegeneration

  • Ismini E. Papageorgiou
  • Andriani F. Fetani
  • Andrea Lewen
  • Uwe Heinemann
  • Oliver Kann
Original Article

Abstract

Activation of microglial cells (brain macrophages) soon after status epilepticus has been suggested to be critical for the pathogenesis of mesial temporal lobe epilepsy (MTLE). However, microglial activation in the chronic phase of experimental MTLE has been scarcely addressed. In this study, we questioned whether microglial activation persists in the hippocampus of pilocarpine-treated, epileptic Wistar rats and to which extent it is associated with segmental neurodegeneration. Microglial cells were immunostained for the universal microglial marker, ionized calcium-binding adapter molecule-1 and the activation marker, CD11b (also known as OX42, Mac-1). Using quantitative morphology, i.e., stereology and Neurolucida-based reconstructions, we investigated morphological correlates of microglial activation such as cell number, ramification, somatic size and shape. We find that microglial cells in epileptic rats feature widespread, activation-related morphological changes such as increase in cell number density, massive up-regulation of CD11b and de-ramification. The parameters show heterogeneity in different hippocampal subregions. For instance, de-ramification is most prominent in the outer molecular layer of the dentate gyrus, whereas CD11b expression dominates in hilus. Interestingly, microglial activation only partially correlates with segmental neurodegeneration. Major neuronal death in the hilus, CA3 and CA1 coincides with strong up-regulation of CD11b. However, microglial activation is also observed in subregions that do not feature neurodegeneration, such as the molecular and granular layer of the dentate gyrus. This in vivo study provides solid experimental evidence that microglial cells feature widespread heterogeneous activation that only partially correlates with hippocampal segmental neuronal loss in experimental MTLE.

Keywords

Microglia CD11b Iba-1 Pilocarpine Neurolucida Stereology 

Abbreviations

AHS

Ammon’s horn sclerosis

CA1

Cornu ammonis subregion 1

CA3

Cornu ammonis subregion 3

CR3

Complement receptor 3

DGgr

Dentate gyrus granular layer

DGmi

Dentate gyrus inner molecular layer

DGmo

Dentate gyrus outer molecular layer

Hil

Hilus

Hipp

Hippocampal formation

Iba-1

Ionized calcium-binding adapter molecule-1

MTLE

Mesial temporal lobe epilepsy

Epi

Chronic epileptic rats

Sub

Subiculum

Sham-subpop

Microglial subpopulation in sham rats

Supplementary material

429_2014_802_MOESM1_ESM.pdf (1 mb)
Supplementary material 1 (PDF 1066 kb)
429_2014_802_MOESM2_ESM.pdf (690 kb)
Supplementary material 2 (PDF 689 kb)
429_2014_802_MOESM3_ESM.pdf (292 kb)
Supplementary material 3 (PDF 291 kb)
429_2014_802_MOESM4_ESM.pdf (70 kb)
Supplementary material 4 (PDF 70 kb)
429_2014_802_MOESM5_ESM.pdf (94 kb)
Supplementary material 5 (PDF 93 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ismini E. Papageorgiou
    • 1
    • 2
  • Andriani F. Fetani
    • 3
  • Andrea Lewen
    • 1
    • 2
  • Uwe Heinemann
    • 3
  • Oliver Kann
    • 1
    • 2
  1. 1.Institute of Physiology and PathophysiologyUniversity of HeidelbergHeidelbergGermany
  2. 2.Interdisciplinary Center for Neurosciences (IZN)University of HeidelbergHeidelbergGermany
  3. 3.Institute of NeurophysiologyCharité-Universitätsmedizin BerlinBerlinGermany

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