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01-07-2015 | Original Article

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

Authors: Ismini E. Papageorgiou, Andriani F. Fetani, Andrea Lewen, Uwe Heinemann, Oliver Kann

Published in: Brain Structure and Function | Issue 4/2015

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.

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Also known as the α-subunit of the complement receptor 3, macrophage antigen-1, integrin α_Mβ₂ and OX42.

Amaral DG, Witter MP (1989) The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31:571–591. doi:10.1016/0306-4522(89)90424-7 PubMedCrossRef

Aronica E, Boer K, van Vliet EA, Redeker S, Baayen JC, Spliet WGM, van Rijen PC, Troost D, Lopes da Silva FH, Wadman WJ, Gorter JA (2007) Complement activation in experimental and human temporal lobe epilepsy. Neurobiol Dis 26:497–511. doi:10.1016/j.nbd.2007.01.015 PubMedCrossRef

Beach TG, Woodhurst WB, MacDonald DB, Jones MW (1995) Reactive microglia in hippocampal sclerosis associated with human temporal lobe epilepsy. Neurosci Lett 191:27–30. doi:10.1016/0304-3940(94)11548-1 PubMedCrossRef

Becker AJ, Chen J, Zien A, Sochivko D, Normann S, Schramm J, Elger CE, Wiestler OD, Blümcke I (2003) Correlated stage- and subfield-associated hippocampal gene expression patterns in experimental and human temporal lobe epilepsy. Eur J Neurosci 18:2792–2802. doi:10.1111/j.1460-9568.2003.02993.x PubMedCrossRef

Blümcke I, Coras R, Miyata H, Özkara C (2012) Defining clinico-neuropathological subtypes of mesial temporal lobe epilepsy with hippocampal sclerosis. Brain Pathol 22:402–411. doi:10.1111/j.1750-3639.2012.00583.x PubMedCrossRef

Borges K, Gearing M, McDermott DL, Smith AB, Almonte AG, Wainer BH, Dingledine R (2003) Neuronal and glial pathological changes during epileptogenesis in the mouse pilocarpine model. Exp Neurol 182:21–34. doi:10.1016/S0014-4886(03)00086-4 PubMedCrossRef

Buckmaster PS, Zhang GF, Yamawaki R (2002) Axon sprouting in a model of temporal lobe epilepsy creates a predominantly excitatory feedback circuit. J Neurosci 22:6650–6658PubMed

Cavalheiro EA, Leite JP, Bortolotto ZA, Turski WA, Ikonomidou C, Turski L (1991) Long-term effects of pilocarpine in rats: structural damage of the brain triggers kindling and spontaneous recurrent seizures. Epilepsia 32:778–782. doi:10.1111/j.1528-1157.1991.tb05533.x PubMedCrossRef

Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan W-B (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758. doi:10.1038/nn1472 PubMedCrossRef

Devinsky O, Vezzani A, Najjar S, de Lanerolle NC, Rogawski MA (2013) Glia and epilepsy: excitability and inflammation. Trends Neurosci 36:174–184. doi:10.1016/j.tins.2012.11.008 PubMedCrossRef

Diamond MS, Garcia-Aguilar J, Bickford JK, Corbi AL, Springer TA (1993) The I domain is a major recognition site on the leukocyte integrin Mac-1 (CD11b/CD18) for four distinct adhesion ligands. J Cell Biol 120:1031–1043. doi:10.1083/jcb.120.4.1031 PubMedCrossRef

Eder C, Schilling T, Heinemann U, Haas D, Hailer N, Nitsch R (1999) Morphological, immunophenotypical and electrophysiological properties of resting microglia in vitro. Eur J Neurosci 11:4251–4261. doi:10.1046/j.1460-9568.1999.00852.x PubMedCrossRef

Engel J Jr (2006) ILAE classification of epilepsy syndromes. Epilepsy Res 70(Suppl 1):S5–S10. doi:10.1016/j.eplepsyres.2005.11.014 PubMedCrossRef

Estrada FS, Hernández VS, López-Hernández E, Corona-Morales AA, Solís H, Escobar A, Zhang L (2012) Glial activation in a pilocarpine rat model for epileptogenesis: a morphometric and quantitative analysis. Neurosci Lett 514:51–56. doi:10.1016/j.neulet.2012.02.055 PubMedCrossRef

Foresti ML, Arisi GM, Katki K, Montañez A, Sanchez RM, Shapiro LA (2009) Chemokine CCL2 and its receptor CCR2 are increased in the hippocampus following pilocarpine-induced status epilepticus. J Neuroinflammation 6:40. doi:10.1186/1742-2094-6-40 PubMedCentralPubMedCrossRef

Grady MS, Charleston JS, Maris D, Witgen BM, Lifshitz J (2003) Neuronal and glial cell number in the hippocampus after experimental traumatic brain injury: analysis by stereological estimation. J Neurotrauma 20:929–941. doi:10.1089/089771503770195786 PubMedCrossRef

Hanisch U-K (2013) Functional diversity of microglia—how heterogeneous are they to begin with? Front Cell Neurosci 7:65. doi:10.3389/fncel.2013.00065 PubMedCentralPubMedCrossRef

Hanisch U-K, Kettenmann H (2007) Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci 10:1387–1394. doi:10.1038/nn1997 PubMedCrossRef

Heinemann U, Gabriel S, Jauch R, Schulze K, Kivi A, Eilers A, Kovacs R, Lehmann T-N (2000) Alterations of glial cell function in temporal lobe epilepsy. Epilepsia 41(Suppl 6):185–189. doi:10.1111/j.1528-1157.2000.tb01579.x CrossRef

Houser CR (1992) Morphological changes in the dentate gyrus in human temporal lobe epilepsy. Epilepsy Res Suppl 7:223–234PubMed

Howard CV, Reed MG (2005) Unbiased stereology: three-dimensional measurement in microscopy, 2nd edn. GarlandScience/BIOS Scientific Publishers, Oxon

Hung J, Chansard M, Ousman SS, Nguyen MD, Colicos MA (2010) Activation of microglia by neuronal activity: results from a new in vitro paradigm based on neuronal-silicon interfacing technology. Brain Behav Immun 24:31–40. doi:10.1016/j.bbi.2009.06.150 PubMedCrossRef

Husemann J, Obstfeld A, Febbraio M, Kodama T, Silverstein SC (2001) CD11b/CD18 mediates production of reactive oxygen species by mouse and human macrophages adherent to matrixes containing oxidized LDL. Arterioscler Thromb Vasc Biol 21:1301–1305. doi:10.1161/hq0801.095150 PubMedCrossRef

Ihanus E, Uotila LM, Toivanen A, Varis M, Gahmberg CG (2007) Red-cell ICAM-4 is a ligand for the monocyte/macrophage integrin CD11c/CD18: characterization of the binding sites on ICAM-4. Blood 109:802–810. doi:10.1182/blood-2006-04-014878 PubMedCrossRef

Ito D, Imai Y, Ohsawa K, Nakajima K, Fukuuchi Y, Kohsaka S (1998) Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57:1–9. doi:10.1016/S0169-328X(98)00040-0 PubMedCrossRef

Jamali S, Salzmann A, Perroud N, Ponsole-Lenfant M, Cillario J, Roll P, Roeckel-Trevisiol N, Crespel A, Balzar J, Schlachter K, Gruber-Sedlmayr U, Pataraia E, Baumgartner C, Zimprich A, Zimprich F, Malafosse A, Szepetowski P (2010) Functional variant in complement C3 gene promoter and genetic susceptibility to temporal lobe epilepsy and febrile seizures. PLoS One 5:e12740. doi:10.1371/journal.pone.0012740 PubMedCentralPubMedCrossRef

Janigro D (2012) Are you in or out? Leukocyte, ion, and neurotransmitter permeability across the epileptic blood-brain barrier. Epilepsia 53(Suppl 1):26–34. doi:10.1111/j.1528-1167.2012.03472.x PubMedCentralPubMedCrossRef

Jinno S, Kosaka T (2008) Reduction of Iba1-expressing microglial process density in the hippocampus following electroconvulsive shock. Exp Neurol 212:440–447. doi:10.1016/j.expneurol.2008.04.028 PubMedCrossRef

Jinno S, Fleischer F, Eckel S, Schmidt V, Kosaka T (2007) Spatial arrangement of microglia in the mouse hippocampus: a stereological study in comparison with astrocytes. Glia 55:1334–1347. doi:10.1002/glia.20552 PubMedCrossRef

Jung K-H, Chu K, Lee S-T, Park K-I, Kim J-H, Kang K-M, Kim S, Jeon D, Kim M, Lee SK, Roh J-K (2011) Molecular alterations underlying epileptogenesis after prolonged febrile seizure and modulation by erythropoietin. Epilepsia 52:541–550. doi:10.1111/j.1528-1167.2010.02916.x PubMedCrossRef

Kann O, Hoffmann A, Schumann RR, Weber JR, Kettenmann H, Hanisch U-K (2004) The tyrosine kinase inhibitor AG126 restores receptor signaling and blocks release functions in activated microglia (brain macrophages) by preventing a chronic rise in the intracellular calcium level. J Neurochem 90:513–525. doi:10.1111/j.1471-4159.2004.02534.x PubMedCrossRef

Kann O, Kovács R, Njunting M, Behrens CJ, Otáhal J, Lehmann T-N, Gabriel S, Heinemann U (2005) Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain 128:2396–2407. doi:10.1093/brain/awh568 PubMedCrossRef

Kettenmann H, Hanisch U-K, Noda M, Verkhratsky A (2011) Physiology of microglia. Physiol Rev 91:461–553. doi:10.1152/physrev.00011.2010 PubMedCrossRef

Kharatishvili I, Shan ZY, She DT, Foong S, Kurniawan ND, Reutens DC (2013) MRI changes and complement activation correlate with epileptogenicity in a mouse model of temporal lobe epilepsy. Brain Struct Funct. doi:10.1007/s00429-013-0528-4 PubMed

Kim J-E, Yeo S-I, Ryu HJ, Kim M-J, Kim D-S, Jo S-M, Kang T-C (2010) Astroglial loss and edema formation in the rat piriform cortex and hippocampus following pilocarpine-induced status epilepticus. J Comp Neurol 518:4612–4628. doi:10.1002/cne.22482 PubMedCrossRef

Lehmann T-N, Gabriel S, Kovacs R, Eilers A, Kivi A, Schulze K, Lanksch WR, Meencke HJ, Heinemann U (2000) Alterations of neuronal connectivity in area CA1 of hippocampal slices from temporal lobe epilepsy patients and from pilocarpine-treated epileptic rats. Epilepsia 41(Suppl 6):190–194. doi:10.1111/j.1528-1157.2000.tb01580.x CrossRef

Lehmann T-N, Gabriel S, Eilers A, Njunting M, Kovacs R, Schulze K, Lanksch WR, Heinemann U (2001) Fluorescent tracer in pilocarpine-treated rats shows widespread aberrant hippocampal neuronal connectivity. Eur J Neurosci 14:83–95. doi:10.1046/j.0953-816x.2001.01632.x PubMedCrossRef

Liaury K, Miyaoka T, Tsumori T, Furuya M, Wake R, Ieda M, Tsuchie K, Taki M, Ishihara K, Tanra AJ, Horiguchi J (2012) Morphological features of microglial cells in the hippocampal dentate gyrus of Gunn rat: a possible schizophrenia animal model. J Neuroinflammation 9:56. doi:10.1186/1742-2094-9-56 PubMedCentralPubMedCrossRef

Libbey JE, Kirkman NJ, Wilcox KS, White HS, Fujinami RS (2010) Role for complement in the development of seizures following acute viral infection. J Virol 84:6452–6460. doi:10.1128/JVI.00422-10 PubMedCentralPubMedCrossRef

Longo B, Romariz S, Blanco MM, Vasconcelos JF, Bahia L, Soares MBP, Mello LE, Ribeiro-dos-Santos R (2010) Distribution and proliferation of bone marrow cells in the brain after pilocarpine-induced status epilepticus in mice. Epilepsia 51:1628–1632. doi:10.1111/j.1528-1167.2010.02570.x PubMedCrossRef

Majores M, Schoch S, Lie A, Becker AJ (2007) Molecular neuropathology of temporal lobe epilepsy: complementary approaches in animal models and human disease tissue. Epilepsia 48(Suppl 2):4–12. doi:10.1111/j.1528-1167.2007.01062.x PubMedCrossRef

Maroso M, Balosso S, Ravizza T, Liu J, Bianchi ME, Vezzani A (2011) Interleukin-1 type 1 receptor/Toll-like receptor signalling in epilepsy: the importance of IL-1beta and high-mobility group box 1. J Intern Med 270:319–326. doi:10.1111/j.1365-2796.2011.02431.x PubMedCrossRef

Mello LEAM, Cavalheiro EA, Tan AM, Kupfer WR, Pretorius JK, Babb TL, Finch DM (1993) Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. Epilepsia 34:985–995. doi:10.1111/j.1528-1157.1993.tb02123.x PubMedCrossRef

Özkara C, Aronica E (2012) Hippocampal sclerosis. Handb Clin Neurol 108:621–639. doi:10.1016/B978-0-444-52899-5.00019-8 PubMedCrossRef

Papageorgiou IE, Gabriel S, Fetani AF, Kann O, Heinemann U (2011) Redistribution of astrocytic glutamine synthetase in the hippocampus of chronic epileptic rats. Glia 59:1706–1718. doi:10.1002/glia.21217 PubMedCrossRef

Pascual O, Ben Achour S, Rostaing P, Triller A, Bessis A (2012) Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc Natl Acad Sci USA 109:e197–e205. doi:10.1073/pnas.1111098109 PubMedCentralPubMedCrossRef

Paxinos G, Watson C (1998) The rat brain in stereotaxic coordinates, 4th edn. Academic Press, San Diego, CA

Pernot F, Heinrich C, Barbier L, Peinnequin A, Carpentier P, Dhote F, Baille V, Beaup C, Depaulis A, Dorandeu F (2011) Inflammatory changes during epileptogenesis and spontaneous seizures in a mouse model of mesiotemporal lobe epilepsy. Epilepsia 52:2315–2325. doi:10.1111/j.1528-1167.2011.03273.x PubMedCrossRef

Pitkänen A, Kharatishvili I, Karhunen H, Lukasiuk K, Immonen R, Nairismägi J, Gröhn O, Nissinen J (2007) Epileptogenesis in experimental models. Epilepsia 48(Suppl 2):13–20. doi:10.1111/j.1528-1167.2007.01063.x PubMedCrossRef

Pocock JM, Kettenmann H (2007) Neurotransmitter receptors on microglia. Trends Neurosci 30:527–535. doi:10.1016/j.tins.2007.07.007 PubMedCrossRef

Priller J, Flügel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernández-Klett F, Prass K, Bechmann I, de Boer BA, Frotscher M, Kreutzberg GW, Persons DA, Dirnagl U (2001) Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med 7:1356–1361. doi:10.1038/nm1201-1356 PubMedCrossRef

Ransohoff RM, Cardona AE (2010) The myeloid cells of the central nervous system parenchyma. Nature 468:253–262. doi:10.1038/nature09615 PubMedCrossRef

Ravizza T, Rizzi M, Perego C, Richichi C, Velískôvá J, Moshé SL, De Simoni MG, Vezzani A (2005) Inflammatory response and glia activation in developing rat hippocampus after status epilepticus. Epilepsia 46(Suppl 5):113–117. doi:10.1111/j.1528-1167.2005.01006.x PubMedCrossRef

Ravizza T, Gagliardi B, Noé F, Boer K, Aronica E, Vezzani A (2008) Innate and adaptive immunity during epileptogenesis and spontaneous seizures: evidence from experimental models and human temporal lobe epilepsy. Neurobiol Dis 29:142–160. doi:10.1016/j.nbd.2007.08.012 PubMedCrossRef

Riazi K, Galic MA, Kuzmiski JB, Ho W, Sharkey KA, Pittman QJ (2008) Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci USA 105:17151–17156. doi:10.1073/pnas.0806682105 PubMedCentralPubMedCrossRef

Rochefort N, Quenech’du N, Watroba L, Mallat M, Giaume C, Milleret C (2002) Microglia and astrocytes may participate in the shaping of visual callosal projections during postnatal development. J Physiol Paris 96:183–192. doi:10.1016/S0928-4257(02)00005-0 PubMedCrossRef

Roseti C, Fucile S, Lauro C, Martinello K, Bertollini C, Esposito V, Mascia A, Catalano M, Aronica E, Limatola C, Palma E (2013) Fractalkine/CX3CL1 modulates GABA_A currents in human temporal lobe epilepsy. Epilepsia 54:1834–1844. doi:10.1111/epi.12354 PubMedCrossRef

Scharfman HE, Sollas AL, Berger RE, Goodman JH (2003) Electrophysiological evidence of monosynaptic excitatory transmission between granule cells after seizure-induced mossy fiber sprouting. J Neurophysiol 90:2536–2547. doi:10.1152/jn.00251.2003 PubMedCrossRef

Schilling T, Nitsch R, Heinemann U, Haas D, Eder C (2001) Astrocyte-released cytokines induce ramification and outward K⁺ channel expression in microglia via distinct signalling pathways. Eur J Neurosci 14:463–473. doi:10.1046/j.0953-816x.2001.01661.x PubMedCrossRef

Schneider CA, Rasband WS, Eliceiri KW (2012) NIH Image to ImageJ: 25 years of image analysis. Nat Methods 9:671–675. doi:10.1038/nmeth.2089 PubMedCrossRef

Scimemi A, Schorge S, Kullmann DM, Walker MC (2006) Epileptogenesis is associated with enhanced glutamatergic transmission in the perforant path. J Neurophysiol 95:1213–1220. doi:10.1152/jn.00680.2005 PubMedCrossRef

Sekeljic V, Bataveljic D, Stamenkovic S, Ułamek M, Jabłoński M, Radenovic L, Pluta R, Andjus PR (2012) Cellular markers of neuroinflammation and neurogenesis after ischemic brain injury in the long-term survival rat model. Brain Struct Funct 217:411–420. doi:10.1007/s00429-011-0336-7 PubMedCrossRef

Shapiro LA, Wang L, Ribak CE (2008) Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia 49(Suppl 2):33–41. doi:10.1111/j.1528-1167.2008.01491.x PubMedCrossRef

Shapiro LA, Perez ZD, Foresti ML, Arisi GM, Ribak CE (2009) Morphological and ultrastructural features of Iba1-immunolabeled microglial cells in the hippocampal dentate gyrus. Brain Res 1266:29–36. doi:10.1016/j.brainres.2009.02.031 PubMedCentralPubMedCrossRef

Shaw JAG, Perry VH, Mellanby J (1990) Tetanus toxin-induced seizures cause microglial activation in rat hippocampus. Neurosci Lett 120:66–69. doi:10.1016/0304-3940(90)90169-A PubMedCrossRef

Sholl DA (1953) Dendritic organization in the neurons of the visual and motor cortices of the cat. J Anat 87:387–406PubMedCentralPubMed

Sloviter RS (2008) Hippocampal epileptogenesis in animal models of mesial temporal lobe epilepsy with hippocampal sclerosis: the importance of the “latent period” and other concepts. Epilepsia 49(Suppl 9):85–92. doi:10.1111/j.1528-1167.2008.01931.x PubMedCrossRef

Sosunov AA, Wu X, McGovern RA, Coughlin DG, Mikell CB, Goodman RR, McKhann GM II (2012) The mTOR pathway is activated in glial cells in mesial temporal sclerosis. Epilepsia 53(Suppl 1):78–86. doi:10.1111/j.1528-1167.2012.03478.x PubMedCrossRef

Steinhäuser C, Seifert G (2002) Glial membrane channels and receptors in epilepsy: impact for generation and spread of seizure activity. Eur J Pharmacol 447:227–237. doi:10.1016/S0014-2999(02)01846-0 PubMedCrossRef

Stence N, Waite M, Dailey ME (2001) Dynamics of microglial activation: a confocal time-lapse analysis in hippocampal slices. Glia 33:256–266. doi:10.1002/1098-1136(200103)33:3<256:AID-GLIA1024>3.0.CO;2-J PubMedCrossRef

Téllez-Zenteno JF, Hernández-Ronquillo L (2012) A review of the epidemiology of temporal lobe epilepsy. Epilepsy Res Treat 2012:ID 630853. doi: 10.1155/2012/630853

Todd RF III (1996) The continuing saga of complement receptor type 3 (CR3). J Clin Invest 98:1–2. doi:10.1172/JCI118752 PubMedCentralPubMedCrossRef

Tooyama I, Bellier J-P, Park M, Minnasch P, Uemura S, Hisano T, Iwami M, Aimi Y, Yasuhara O, Kimura H (2002) Morphologic study of neuronal death, glial activation, and progenitor cell division in the hippocampus of rat models of epilepsy. Epilepsia 43(Suppl 9):39–43. doi:10.1046/j.1528-1157.43.s.9.10.x PubMedCrossRef

Ulmann L, Levavasseur F, Avignone E, Peyroutou R, Hirbec H, Audinat E, Rassendren F (2013) Involvement of P2X4 receptors in hippocampal microglial activation after status epilepticus. Glia 61:1306–1319. doi:10.1002/glia.22516 PubMedCrossRef

van Strien NM, Cappaert NLM, Witter MP (2009) The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. Nat Rev Neurosci 10:272–282. doi:10.1038/nrn2614 PubMedCrossRef

Vezzani A, French J, Bartfai T, Baram TZ (2011) The role of inflammation in epilepsy. Nat Rev Neurol 7:31–40. doi:10.1038/nrneurol.2010.178 PubMedCentralPubMedCrossRef

Wennström M, Hellsten J, Ekstrand J, Lindgren H, Tingström A (2006) Corticosterone-induced inhibition of gliogenesis in rat hippocampus is counteracted by electroconvulsive seizures. Biol Psychiatry 59:178–186. doi:10.1016/j.biopsych.2005.08.032 PubMedCrossRef

West MJ, Slomianka L, Gundersen HJG (1991) Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat Rec 231:482–497. doi:10.1002/ar.1092310411 PubMedCrossRef

Wirenfeldt M, Dissing-Olesen L, Babcock AA, Nielsen M, Meldgaard M, Zimmer J, Azcoitia I, Leslie RGQ, Dagnaes-Hansen F, Finsen B (2007) Population control of resident and immigrant microglia by mitosis and apoptosis. Am J Pathol 171:617–631. doi:10.2353/ajpath.2007.061044 PubMedCentralPubMedCrossRef

Yang T-T, Lin C, Hsu C-T, Wang T-F, Ke F-Y, Kuo Y-M (2013) Differential distribution and activation of microglia in the brain of male C57BL/6J mice. Brain Struct Funct 218:1051–1060. doi:10.1007/s00429-012-0446-x PubMedCrossRef

Zattoni M, Mura ML, Deprez F, Schwendener RA, Engelhardt B, Frei K, Fritschy J-M (2011) Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. J Neurosci 31:4037–4050. doi:10.1523/JNEUROSCI.6210-10.2011 PubMedCrossRef

Zhang W, Huguenard JR, Buckmaster PS (2012) Increased excitatory synaptic input to granule cells from hilar and CA3 regions in a rat model of temporal lobe epilepsy. J Neurosci 32:1183–1196. doi:10.1523/JNEUROSCI.5342-11.2012 PubMedCentralPubMedCrossRef

Title: Widespread activation of microglial cells in the hippocampus of chronic epileptic rats correlates only partially with neurodegeneration
Authors: Ismini E. Papageorgiou
Andriani F. Fetani
Andrea Lewen
Uwe Heinemann
Oliver Kann
Publication date: 01-07-2015
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 4/2015
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-014-0802-0

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

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