caa a22 4500 606202625 CHVBK 20210128100954.0 cr unu---uuuuu 210128e20150701xx s 000 0 eng 10.1007/s00429-014-0802-0 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0802-0 Widespread activation of microglial cells in the hippocampus of chronic epileptic rats correlates only partially with neurodegeneration [Elektronische Daten] [Ismini Papageorgiou, Andriani Fetani, Andrea Lewen, Uwe Heinemann, Oliver Kann] 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. Springer-Verlag Berlin Heidelberg, 2014 Microglia nationallicence CD11b nationallicence Iba-1 nationallicence Pilocarpine nationallicence Neurolucida nationallicence Stereology nationallicence AHS : Ammon's horn sclerosis nationallicence CA1 : Cornu ammonis subregion 1 nationallicence CA3 : Cornu ammonis subregion 3 nationallicence CR3 : Complement receptor 3 nationallicence DGgr : Dentate gyrus granular layer nationallicence DGmi : Dentate gyrus inner molecular layer nationallicence DGmo : Dentate gyrus outer molecular layer nationallicence Hil : Hilus nationallicence Hipp : Hippocampal formation nationallicence Iba-1 : Ionized calcium-binding adapter molecule-1 nationallicence MTLE : Mesial temporal lobe epilepsy nationallicence Epi : Chronic epileptic rats nationallicence Sub : Subiculum nationallicence Sham-subpop : Microglial subpopulation in sham rats nationallicence Papageorgiou Ismini Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany aut Fetani Andriani Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany aut Lewen Andrea Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany aut Heinemann Uwe Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany aut Kann Oliver Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany aut Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2423-2439 1863-2653 220:4<2423 2015 220 429 https://doi.org/10.1007/s00429-014-0802-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0802-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Papageorgiou Ismini Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- Fetani Andriani Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany aut NATIONALLICENCE 700 1- Lewen Andrea Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany aut NATIONALLICENCE 700 1- Heinemann Uwe Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, Berlin, Germany aut NATIONALLICENCE 700 1- Kann Oliver Institute of Physiology and Pathophysiology, University of Heidelberg, Im Neuenheimer Feld 326, 69120, Heidelberg, Germany aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/4(2015-07-01), 2423-2439 1863-2653 220:4<2423 2015 220 429