Organotypic brain slice cultures: A review
Open accessAbstract
In vitro cell cultures are an important tool for obtaining insights into cellular processes in an isolated system and a supplement to in vivo animal experiments. While primary dissociated cultures permit a single homogeneous cell population to be studied, there is a clear need to explore the function of brain cells in a three-dimensional system where the main architecture of the cells is preserved. Thus, organotypic brain slice cultures have proven to be very useful in investigating cellular and molecular processes of the brain in vitro. This review summarizes (1) the historical development of organotypic brain slices focusing on the membrane technology, (2) methodological aspects regarding culturing procedures, age of donors or media, (3) whether the cholinergic neurons serve as a model of neurodegeneration in Alzheimer's disease, (4) or the nigrostriatal dopaminergic neurons as a model of Parkinson's disease and (5) how the vascular network can be studied, especially with regard to a synthetic blood-brain barrier. This review will also highlight some limits of the model and give an outlook on future applications.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Diffusion of glutamate to cells in BSC is slower than in cell cultures, which means BSC require higher concentrations of glutamate to achieve toxic effects.
“First, the diffusion of glutamate to the cells in BSC is slower than in cell cultures, which means BSC require higher concentrations of glutamate to achieve toxic effects (Humpel, 2015).”
From Toxic Concentrations of Glutamate Induce Ferroptosis without Affecting Mitochondrial Respiration in Rodent Brain Slice Cultures (2026) · cites this paper as Humpel, 2015
In “Applications using organotypic brain slices” (page unavailable), Humpel reports that slices need markedly higher doses of a toxic stimulus than primary cells. The passage does not identify glutamate as that stimulus or say that slower glutamate diffusion explains the difference. (LLM, conf=0.87)
Experimental — accuracy not yet measuredOrganotypic culture allows the study of the brain in its original structure.
“This technique allows the study of the brain in its original structure [19, 20].”
From Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer’s disease (2021) · cites this paper as [20]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Cerebral organoids model human brain development and microcephaly
Lancaster, M. A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L. S., Hurles, M. E., Homfray, T., Penninger, J. M., Jackson, A. P., & Knoblich, J. A. (2013) · Nature · doi:10.1038/nature12517 · Cited by 5,372 · see citing works
A three-dimensional human neural cell culture model of Alzheimer’s disease
Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D’Avanzo, C., Chen, H., Hooli, B., Asselin, C., Muffat, J., et al. (2014) · Nature · doi:10.1038/nature13800 · Cited by 1,195 · see citing works
Three-dimensional organotypic culture: experimental models of mammalian biology and disease
Shamir, E. R., & Ewald, A. J. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3873 · Cited by 719 · see citing works
Rosenstein, J. M., Mani, N., Khaibullina, A., & Krum, J. M. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-35-11036.2003 · Cited by 220 · see citing works
Flagged first, then by citations
Research works printed but not linked: 151
- af Bjerkén S Boger HA Nelson M Hoffer BJ Granholm AC Strömberg I Effects of glial cell line-derived neurotrophic factor deletion on ventral mesencephalic organotypic tissue cultures Brain Res 2007 1133 10 19 17184739 PMC2670563
- Alberdi E Sánchez-Gómez MV Cavaliere F Pérez-Samartín A Zugaza JL Trullas R Domercq M Matute C Amyloid beta oligomers induce Ca2+ dysregulation and neuronal death through activation of ionotropic glutamate receptors Cell Calcium 2010 47 3 264 272 20061018
- Allen YS Devanathan PH Owen GP Neurotoxicity of beta-amyloid protein: cytochemical changes and apoptotic cell death investigated in organotypic cultures Clin Exp Pharmacol Physiol 1995 22 370 371 7554434
- Annis CM Edmond J Robertson RT A chemically-defined medium for organotypic slice cultures J Neurosci Methods 1990 32 63 70 1970842
- Ansevin KD Lipps BV Tissue plate: a new technique for long-termorganotypic culture In Vitro 1973 8 483 488 4725695
- Auerbach R Lewis R Shinners B Kubai L Akhtar N Angiogenesis assays: a critical overview Clin Chem 2003 49 32 40 12507958
- Bahr BA Long-term hippocampal slices: a model system for investigating synaptic mechanisms and pathologic processes J Neurosci Res 1995 42 3 294 305 8583497
- Beach RL Bathgate SL Cotman CW Identification of cell types in rat hippocampal slices maintained in organotypic cultures Brain Res 1982 255 3 20 7034866
- Bendfeldt K Radojevic V Kapfhammer J Nitsch C Basic fibroblast growth factor modulates density of blood vessels and preserves tight junctions in organotypic cortical cultures of mice: a new in vitro model of the blood–brain barrier J Neurosci 2007 27 12 3260 3267 17376986 PMC6672460
- Bergold PJ Casaccia-Bonnefil P Preparation of organotypic hippocampal slice cultures using the membrane filter method Methods Mol Biol 1997 72 15 22 9249734
- Bousquet J Meunier JM Organotypic culture, on natural and artificial media, of fragments of the adult rat hypophysis C R Seances Soc Biol Fil 1962 156 65 67 13871954
- Boyd WH A chamber for organotypic culture; adapted for growing large volumes of tissue Stain Technol 1971 46 85 87 5106017
- Braschler UF Iannone A Spenger C Streit J Lüscher HR A modified roller tube technique for organotypic cocultures of embryonic rat spinal cord, sensory ganglia and skeletal muscle J Neurosci Methods 1989 29 121 129 2770335
- Breen A O’Brien T Pandit A Fibrin as a delivery system for therapeutic drugs and biomolecules Tissue Eng Part B Rev 2009 15 201 214 19249942
- Bruce AJ Malfroy B Baudry M Beta-amyloid toxicity in organotypic hippocampal cultures: protection by EUK-8, a synthetic catalytic free radical scavenger Proc Natl Acad Sci U S A 1996 93 2312 2316 8637869 PMC39792
- Buchs PA Stoppini L Muller D Structural modifications associated with synaptic development in area CA1 of rat hippocampal organotypic cultures Brain Res Dev Brain Res 1993 71 81 91 8432003
- Camenzind RS Chip S Gutmann H Kapfhammer JP Nitsch C Bendfeldt K Preservation of transendothelial glucose transporter 1 and P-glycoprotein transporters in a cortical slice culture model of the blood-brain barrier Neuroscience 2010 170 1 361 371 20603190
- Cavaliere F Vicente ES Matute C An organotypic culture model to study nigro-striatal degeneration J Neurosci Methods 2010 188 205 212 20153372
- Ceccariglia S D’Altocolle A Del Fa’ A Pizzolante F Caccia E Michetti F Gangitano C Cathepsin D plays a crucial role in the trimethyltin-induced hippocampal neurodegeneration process Neuroscience 2011 174 160 170 21111789
- Chip S Nitsch C Wellmann S Kapfhammer JP Subfield-specific neurovascular remodeling in the entorhino-hippocampal-organotypic slice culture as a response to oxygen–glucose deprivation and excitotoxic cell death J Cereb Blood Flow Metab 2013 33 4 508 518 23232944 PMC3618384
- Chip S Zhu X Kapfhammer JP The analysis of neurovascular remodeling in entorhino-hippocampal organotypic slice cultures J Vis Exp 2014 92 e52023 http://dx.doi.org/10.3791/52023 25408363 PMC4353386 · DOI
- Chong YH Shin YJ Lee EO Kayed R Glabe CG Tenner AJ ERK1/2 activation mediates Abeta oligomer-induced neurotoxicity via caspase-3 activation and tau cleavage in rat organotypic hippocampal slice cultures J Biol Chem 2006 281 20315 20325 16714296
- Clapp-Lilly KL Smith MA Perry G Harris PL Zhu X Duffy LK Melatonin acts as mantioxidant and pro-oxidant in an organotypic slice culture model of Alzheimer’s disease NeuroReport 2001 12 1277 1280 11338206
- Crain SM Development of “organotypic” bioelectric activities in central nervous tissues during maturation in culture Int Rev Neurobiol 1966 9 1 43 5337726
- Crain SM Bornstein MB Organotypic bioelectric activity in cultured reaggregates of dissociated rodent brain cells Science 1972 176 182 184 5014441
- Crain SM Peterson ER Enhanced afferent synaptic functions in fetal mouse spinal cord-sensory ganglion explants following NGF-induced ganglion hypertrophy Brain Res 1974 79 1 145 152 4473249
- Daschil N Kniewallner KM Obermair GJ Hutter-Paier B Windisch M Marksteiner J Humpel C L-Type calcium channel blockers and substance P induce angiogenesis of cortical vessels associated with beta-amyloid plaques in an Alzheimer mouse model Neurobiol Aging 2015 http://dx.doi.org/10.1016/j.neurobiolaging.2014.12.027. S0197-4580(14)00844-6. [Epub ahead of print] PMC4347662 25619662 · DOI
- Daviaud N Garbayo E Schiller PC Perez-Pinzon M Montero-Menei CN Organotypic cultures as tools for optimizing central nervous system cell therapies Exp Neurol 2013 248 429 440 23899655
- Daviaud N Garbayo E Lautram N Franconi F Lemaire L Perez-Pinzon M Montero-Menei CN Modeling nigrostriatal degeneration in organotypic cultures, a new ex vivo model of Parkinson’s disease Neuroscience 2014 256 10 22 24161279 PMC4104532
- De Simoni A Yu LM Preparation of organotypic hippocampal slice cultures: interface method Nat Protoc 2006 1 1439 1445 17406432
- del Rio JA Heimrich B Soriano E Schwegler H Frotscher M Proliferation and differentiation of glial fibrillary acidic protein-immunoreactive glial cells in organotypic slice cultures of rat hippocampus Neuroscience 1991 43 335 347 1922776
- del Río JA Heimrich B Supèr H Borrell V Frotscher M Soriano E Differential survival of Cajal-Retzius cells in organotypic cultures of hippocampus and neocortex J Neurosci 1996 16 21 6896 6907 8824328 PMC6579265
- Dixon SJ Lemberg KM Lamprecht MR Skouta R Zaitsev EM Gleason CE Patel DN Bauer AJ Cantley AM Yang WS Morrison B 3rd Stockwell BR Ferroptosis: an iron-dependent form of nonapoptotic cell death Cell 2012 149 5 1060 1072 22632970 PMC3367386
- Dong HW Buonomano DV A technique for repeated recordings in cortical organotypic slices J Neurosci Methods 2005 146 69 75 15935222
- Drexler B Hentschke H Antkowiak B Grasshoff C Organotypic cultures as tools for testing neuroactive drugs – link between in-vitro and in-vivo experiments Curr Med Chem 2010 17 4538 4550 21062252
- Duff K Noble W Gaynor K Matsuoka Y Organotypic slice cultures from transgenic mice as disease model systems J Mol Neurosci 2002 19 317 320 12540058
- Duport S Robert F Muller D Grau G Parisi L Stoppini L An in vitro blood-brain barrier model: cocultures between endothelial cells and organotypic brain slice cultures Proc Natl Acad Sci U S A 1998 95 1840 1845 9465104 PMC19200
- Egert U Schlosshauer B Fennrich S Nisch W Fejtl M Knott T Müller T Hämmerle H A novel organotypic long-term culture of the rat hippocampus on substrate-integrated multielectrode arrays Brain Res Brain Res Protoc 1998 2 229 242 9630647
- Eugene E Cluzeaud F Cifuentes-Diaz C Fricker D Le Duigou C Clemenceau S Baulac M Poncer JC Miles R An organotypic brain slice preparation from adult patients with temporal lobe epilepsy J Neurosci Methods 2014 235 234 244 25064188 PMC4426207
- Franke H Schelhorn N Illes P Dopaminergic neurons develop axonal projections to their target areas in organotypic co-cultures of the ventral mesencephalon and the striatum/prefrontal cortex Neurochem Int 2003 42 431 439 12510026
- Frozza RL Horn AP Hoppe JB Simão F Gerhardt D Comiran RA Salbego CG A comparative study of beta-amyloid peptides Abeta1-42 and Abeta25-35 toxicity in organotypic hippocampal slice cultures Neurochem Res 2009 34 295 303 18686032
- Gähwiler BH Morphological differentiation of nerve cells in thin organotypic cultures derived from rat hippocampus and cerebellum Proc R Soc Lond B Biol Sci 1981a 211 287 290 6111800
- Gähwiler BH Organotypic monolayer cultures of nervous tissue J Neurosci Methods 1981b 4 329 342 7033675
- Gähwiler BH Organotypic cultures of neural tissue Trends Neurosci 1988 11 484 489 2469173
- Gähwiler BH Hefti F Guidance of acetylcholinesterase-containing fibers by target tissue in co-cultured brain slices Neuroscience 1984 40 235 243 6527774
- Gähwiler BH Rietschin L Knöpfel T Enz A Continuous presence of nerve growth factor is required for maintenance of cholinergic septal neurons in norganotypic slice cultures Neuroscience 1990 36 27 31 2215921
- Gähwiler BH Capogna M Debanne D McKinney RA Thompson SM Organotypic slice cultures: a technique has come of age Trends Neurosci 1997 20 471 477 9347615
- Gähwiler BH Thompson SM Muller D Preparation and maintenance of organotypic slice cultures of CNS tissue Curr Protoc Neurosci 2001 Chapter 6: Unit 6.11 18428510
- Gerfin-Moser A Monyer H In situ hybridization on organotypic slice cultures Int Rev Neurobiol 2002 47 125 134 12198797
- Giesing M Neumann G Egge H Zilliken F Lipid metabolism of developing central nervous tissues in organotypic cultures. I. Lipid distribution and fatty acid profiles of the medium for rat brain cortex in vitro Nutr Metab 1975 19 242 250 1232595
- Gogolla N Galimberti I DePaola V Caroni P Long-term live imaging of neuronal circuits in organotypic hippocampal slice cultures Nat Protoc 2006 1 1223 1226 17406405
- Guy Y Rupert AE Sandberg M Weber SG A simple method for measuring organotypic tissue slice culture thickness J Neurosci Methods 2011 199 78 81 21497166 PMC3112260
- Harris-White ME Chu T Balverde Z Sigel JJ Flanders KC Frautschy SA Effects of transforming growth factor-beta (isoforms 1–3) on amyloid-beta deposition, inflammation, and cell targeting in organotypic hippocampal slice cultures J Neurosci 1998 18 10366 10374 9852574 PMC6793343
- Hauw JJ Berger B Escourolle R Presence of synapses in organotypic culture in vitro of human cerebellum C R Acad Sci Hebd Seances Acad Sci D 1972 274 264 266 4622074
- Heine C Franke H Organotypic slice co-culture systems to study axon regeneration in the dopaminergic system ex vivo Methods Mol Biol 2014 1162 97 111 24838961
- Hendelman WJ Marshall KC Ferguson R Carrière S Catecholamine neurons of the central nervous system in organotypic culture Dev Neurosci 1982 5 64 76 7106017
- Henschen A Hoffer B Olson L Spinal cord grafts in oculo: survival, growth, histological organization and electrophysiological characteristics Exp Brain Res 1985 60 1 38 47 4043280
- Hochstrasser T Ullrich C Sperner-Unterweger B Humpel C Inflammatory stimuli reduce survival of serotonergic neurons and induce neuronal expression of indoleamine 2,3-dioxygenase in rat dorsal raphe nucleus organotypic brain slices Neuroscience 2011 184 128 138 21501664
- Hoffer B Seiger A Ljungberg T Olson L Electrophysiological and cytological studies of brain homografts in the anterior chamber of the eye: maturation of cerebellar cortex in oculo Brain Res 1974 79 2 165 184 4424939
- Honegger P Lenoir D Nerve growth factor (NGF) stimulation of cholinergic telencephalic neurons in aggregating cell cultures Brain Res 1982 55 2 229 238 7055724
- Humpel C Organotypic vibrosections from whole brain adult Alzheimer mice (overexpressing amyloid-precursor-protein with the Swedish-Dutch-Iowa mutations) as a model to study clearance of beta-amyloid plaques Front Aging Neurosci 2015 7 47 http://dx.doi.org/10.3389/fnagi.2015.00047 25914642 PMC4391240 · DOI
- Humpel C Weis C Nerve growth factor and cholinergic CNS neurons studied in organotypic brain slices. Implication in Alzheimer’s disease? J Neural Transm Suppl 2002 62 253 263 12456068
- Irmady K Jackman KA Padow VA Shahani N Martin LA Cerchietti L Unsicker K Iadecola C Hempstead BL Mir-592 regulates the induction and cell death-promoting activity of p75NTR in neuronal ischemic injury J Neurosci 2014 34 9 3419 3428 24573298 PMC3935094
- Jaeger C Gonzalo Ruiz A Llinás R Organotypic slice cultures of dopaminergic neurons of substantia nigra Brain Res Bull 1989 22 981 991 2571398
- Jahnsen H Kristensen BW Thiébaud P Noraberg J Jakobsen B Bove M Martinoia S Koudelka-Hep M Grattarola M Zimmer J Coupling of organotypic brain slice cultures to silicon-based arrays of electrodes Methods 1999 18 160 172 10356346
- Jaumotte JD Zigmond MJ Dopaminergic innervation of forebrain by ventral mesencephalon in organotypic slice co-cultures: effects of GDNF Brain Res Mol Brain Res 2005 134 139 146 15790537
- Johansson S Jämsä A Vasänge M Winblad B Luthman J Cowburn RF Increased tau phosphorylation at the Ser396 epitope after amyloid beta-exposure in organotypic cultures NeuroReport 2006 17 907 911 16738486
- Jonakait GM Schotland S Ni L Development of serotonin, substance P and thyrotrophin-releasing hormone in mouse medullary raphe grown in organotypic tissue culture: developmental regulation by serotonin Brain Res 1988 473 336 343 2466525
- Karpiak VC Plenz D Preparation and maintenance of organotypic cultures for multi-electrode array recordings Curr Protoc Neurosci 2002 Chapter 6: Unit 6.15 18428563
- Keller F Rimvall K Waser PG Choline acetyltransferase in organotypic cultures of rat septum and hippocampus Neurosci Lett 1983 42 273 278 6664633
- Kida E Ultrastructural properties of rat substantia nigra in organotypic culture Neuropatol Pol 1986 24 145 159 3785685
- Kim H Kim E Park M Lee E Namkoong K Organotypic hippocampal slice culture from the adult mouse brain: a versatile tool for translational neuropsychopharmacology Prog Neuropsychopharmacol Biol Psychiatry 2013 41 36 43 23159795
- Kiyotani T Teramachi M Takimoto Y Nakamura T Shimizu Y Endo K Nerve regeneration across a 25-mm gap bridged by a polyglycolic acid-collagen tube: a histological and electrophysiological evaluation of regenerated nerves Brain Res 1996 740 66 74 8973799
- Knöpfel T Rietschin L Gähwiler BH Organotypic co-cultures of rat locus coeruleus and hippocampus Eur J Neurosci 1989 1 678 689 12106126
- Koch H Huh SE Elsen FP Carroll MS Hodge RD Bedogni F Turner MS Hevner RF Ramirez JM Prostaglandin E2-induced synaptic plasticity in neocortical networks of organotypic slice cultures J Neurosci 2010 30 35 11678 11687 20810888 PMC3842478
- Kovács R Papageorgiou I Heinemann U Slice cultures as a model to study neurovascular coupling and blood brain barrier in vitro Cardiovasc Psychiatry Neurol 2011 2011 646958 21350722 PMC3042620
- Kremer C Breier G Risau W Plate KH Up-regulation of flk-1/vascular endothelial growth factor receptor 2 by its ligand in a cerebral slice culture system Cancer Res 1997 57 17 3852 3859 9288799
- Kreutz F Frozza RL Breier AC de Oliveira VA Horn AP Pettenuzzo LF Netto CA Salbego CG Trindade VM Amyloid-beta induced toxicity involves ganglioside expression and is sensitive to GM1 neuroprotective action Neurochem Int 2011 59 5 648 655 21723896
- Kristensen BW Noraberg J Thiebaud P Koudelka-Hep M Zimmer J Biocompatibility of silicon-based arrays of electrodes coupled to organotypic hippocampal brain slice cultures Brain Res 2001 896 1 17 11277967
- LaVail JH Wolf MK Postnatal development of the mouse dentate gyrus in organotypic cultures of the hippocampal formation Am J Anat 1973 137 47 65 4703045
- Leggett C McGehee DS Mastrianni J Yang W Bai T Brorson JR Tunicamycin produces TDP-43 cytoplasmic inclusions in cultured brain organotypic slices J Neurol Sci 2012 317 1–2 66 73 22459357 PMC3359826
- Levi-Montalcini R Dal Toso R della Valle F Skaper SD Leon A Update of the NGF saga J Neurol Sci 1995 130 2 119 127 8586974
- Loffredo Sampaolo C Sampaolo G Organotypic cultures of chick embryo lung; some histologic and histochemical aspects Boll Soc Ital Biol Sper 1956 32 797 801 13404150
- Lossi L Alasia S Salio C Merighi A Cell death and proliferation in acute slices and organotypic cultures of mammalian CNS Prog Neurobiol 2009 88 221 245 19552996
- Lossi L Gambino G Salio C Merighi A Autophagy regulates the post-translational cleavage of BCL-2 and promotes neuronal survival ScientificWorldJournal 2010 10 924 929 20495771 PMC5763967
- Maher MP Pine J Wright J Tai Y-C The neurochip: a new multielectrode device for stimulating and recording from cultured neurons J Neurosci Methods 1999 87 45 56 10065993
- Marksteiner J Humpel C Beta-amyloid expression, release and extracellular deposition in aged rat brain slices Mol Psychiatry 2008 13 939 952 17712316
- Marx U Organotypic tissue culture for substance testing J Biotechnol 2010 148 1 2 20620609
- Mazzone GL Mladinic M Nistri A Excitotoxic cell death induces delayed proliferation of endogenous neuroprogenitor cells in organotypic slice cultures of the rat spinal cord Cell Death Dis 2013 4 e902 24176860 PMC3920932
- Mewes A Franke H Singer D Organotypic brain slice cultures of adult transgenic P301S mice–a model for tauopathy studies PLoS One 2012 7 e45017 22984603 PMC3439393
- Mishra A O’Farrell FM Reynell C Hamilton NB Hall CN Attwell D Imaging pericytes and capillary diameter in brain slices and isolated retinae Nat Protoc 2014 9 323 336 24434801
- Monesi V Differentiation of argyrophil and argentaffin cells in organotypic cultures of embryonic chick intestine J Embryol Exp Morphol 1960 8 302 313 13771996
- Morin-Brureau M Lebrun A Rousset MC Fagni L Bockaert J de Bock F Lerner-Natoli M Epileptiform activity induces vascular remodeling and zonula occludens 1 downregulation in organotypic hippocampal cultures: role of VEGF signaling pathways J Neurosci 2011 31 10677 10688 21775611 PMC6622643
- Morin-Brureau M De Bock F Lerner-Natoli M Organotypic brain slices: a model to study the neurovascular unit micro-environment in epilepsies Fluids Barriers CNS 2013 10 11 23391266 PMC3605299
- Moroni F Formentini L Gerace E Camaioni E Pellegrini-Giampietro DE Chiarugi A Pellicciari R Selective PARP-2 inhibitors increase apoptosis in hippocampal slices but protect cortical cells in models of post-ischaemic brain damage Br J Pharmacol 2009 157 5 854 862 19422384 PMC2721269
- Moser KV Schmidt-Kastner R Hinterhuber H Humpel C Brain capillaries and cholinergic neurons persist in organotypic brain slices in the absence of blood flow Eur J Neurosci 2003 18 85 94 12859340
- Moser KV Reindl M Blasig I Humpel C Brain capillary endothelial cells proliferate in response to NGF, express NGF receptors and secrete NGF after inflammation Brain Res 2004 1017 53 60 15261099
- Muller D Buchs PA Stoppini L Time course of synaptic development in hippocampal organotypic cultures Brain Res Dev Brain Res 1993 71 93 100 8432004
- Muller D Stoppini L Wang C Kiss JZ A role for polysialylated neural cell adhesion molecule in lesion-induced sprouting in hippocampal organotypic cultures Neuroscience 1994 61 3 441 445 7969921
- Murphy RC Messer A Gene transfer methods for CNS organotypic cultures: a comparison of three nonviral methods Mol Ther 2001 3 113 121 11162318
- Nassif M Hoppe J Santin K Frozza R Zamin LL Simão F Horn AP Salbego C Beta-amyloid peptide toxicity in organotypic hippocampal slice culture involves Akt/PKB, GSK-3beta, and PTEN Neurochem Int 2007 50 229 235 17018242
- Noraberg J Organotypic brain slice cultures: an efficient and reliable method for neurotoxicological screening and mechanistic studies Altern Lab Anim 2004 32 329 337 15651916
- Olson L Backlund EO Freed W Herrera-Marschitz M Hoffer B Seiger A Strömberg I Transplantation of monoamine-producing cell systems in oculo and intracranially: experiments in search of a treatment for Parkinson’s disease Ann N Y Acad Sci 1985 457 105 126 3913358
- Ostergaard K Schou JP Zimmer J Rat ventral mesencephalon grown as organotypic slice cultures and co-cultured with striatum, hippocampus, and cerebellum Exp Brain Res 1990 82 547 565 1981356
- Ostergaard K Schou JP Gähwiler BH Zimmer J Tyrosine hydroxylase immunoreactive neurons in organotypic slice cultures of the rat striatum and neocortex Exp Brain Res 1991 83 357 365 1673660
- Ostergaard K Finsen B Zimmer J Organotypic slice cultures of the rat striatum: an immunocytochemical, histochemical and in situ hybridization study of somatostatin, neuropeptide Y, nicotinamide adenine dinucleotide phosphate-diaphorase, and enkephalin Exp Brain Res 1995 103 70 84 7615039
- Peterson ER Crain SM Innervation in cultures of fetal rodent skeletal muscle by organotypic explants of spinal cord from different animals Z Zellforsch Mikrosk Anat 1970 106 1 21 5449068
- Plenz D Kitai ST Organotypic cortex-striatum-mesencephalon cultures: the nigrostriatal pathway Neurosci Lett 1996 209 177 180 8736639
- Prasanthi JR Larson T Schommer J Ghribi O Silencing GADD153/CHOP gene expression protects against Alzheimer’s disease-like pathology induced by 27-hydroxycholesterol in rabbit hippocampus PLoS One 2011 6 e26420 22046282 PMC3194795
- Quadros A Patel N Crescentini R Crawford F Paris D Mullan M Increased TNFalpha production and Cox-2 activity in organotypic brain slice cultures from APPsw transgenic mice Neurosci Lett 2003 353 66 68 14642439
- Reinbold R Organotypic differentiation of the eye of the chick embryo in vitro C R Seances Soc Biol Fil 1954 148 1493 1495 14352543
- Renkawek K Murray MR Spatz M Klatzo I Distinctive histochemical characteristics of brain capillaries in organotypic culture Exp Neurol 1976 50 194 206 2486
- Ridoux V Robert J Perricaudet M Mallet J Le Gal La.Salle G Adenovirus mediated gene transfer in organotypic brain slices Neurobiol Dis 1995 2 49 54 8980008
- Robain O Barbin G Billette de Villemeur T Jardin L Jahchan T Ben-Ari Y Development of mossy fiber synapses in hippocampal slice culture Brain Res Dev Brain Res 1994 80 1–2 244 250 7955349
- Robertson RT Baratta J Kageyama GH Ha DH Yu J Specificity of attachment and neurite outgrowth of dissociated basal forebrain cholinergic neurons seeded on to organotypic slice cultures of forebrain Neuroscience 1997 80 741 752 9276490
- Rosenstein JM Mani N Silverman WF Krum JM Patterns of brain angiogenesis after vascular endothelial growth factor administration in vitro and in vivo Proc Natl Acad Sci U S A 1998 95 12 7086 7091 9618543 PMC22748
- Schatz DS Kaufmann WA Saria A Humpel C Dopamine neurons in a simple GDNF-treated meso-striatal organotypic co-culture model Exp Brain Res 1999 127 270 278 10452214
- Schrag M Sharma S Brown-Borg H Ghribi O Hippocampus of Ames dwarf mice is resistant to beta-amyloid-induced tau hyperphosphorylation and changes in apoptosis-regulatory protein levels Hippocampus 2008 18 3 239 244 18000817
- Scuderi C Valenza M Stecca C Esposito G Carratù MR Steardo L Palmitoylethanolamide exerts neuroprotective effects in mixed neuroglial cultures and organotypic hippocampal slices via peroxisome proliferator-activated receptor-alpha J Neuroinflammation 2012 9 49 22405189 PMC3315437
- Sedel F Béchade C Triller A Nerve growth factor (NGF) induces motoneuron apoptosis in rat embryonic spinal cord in vitro Eur J Neurosci 1999 11 3904 3912 10583479
- Simões Pires EN Frozza RL Hoppe JB Menezes Bde M Salbego CG Berberine was neuroprotective against an in vitro model of brain ischemia: survival and apoptosis pathways involved Brain Res 2014 1557 26 33 24560603
- Snyder-Keller A Costantini LC Graber DJ Development of striatal patch/matrix organization in organotypic co-cultures of perinatal striatum, cortex an substantia nigra Neuroscience 2001 103 97 109 11311790
- Stahl K Skare Ø Torp R Organotypic cultures as a model of Parkinson s disease. A twist to an old model ScientificWorldJournal 2009 9 811 821 19705040 PMC5823196
- Staton CA Stribbling SM Tazzyman S Hughes R Brown NJ Lewis CE Current methods for assaying angiogenesis in vitro and in vivo Int J Exp Pathol 2004 85 33 48 PMC2517524 15379956
- Staton CA Reed MW Brown NJ A critical analysis of current in vitro and in vivo angiogenesis assays Int J Exp Pathol 2009 90 195 221 19563606 PMC2697546
- Stoppini L Buchs PA Muller D A simple method for organotypic cultures of nervous tissue J Neurosci Methods 1991 37 173 182 1715499
- Stoppini L Buchs PA Muller D Lesion-induced neurite sprouting and synapse formation in hippocampal organotypic cultures Neuroscience 1993 57 4 985 994 8309556
- Suh EC Jung YJ Kim YA Park EM Lee KE A beta 25–35 induces presynaptic changes in organotypic hippocampal slice cultures Neurotoxicology 2008 29 691 699 18502514
- Sundstrom L Morrison B 3rd Bradley M Pringle A Organotypic cultures as tools for functional screening in the CNS Drug Discov Today 2005 10 993 1000 16023058
- Tardito D Gennarelli M Musazzi L Gesuete R Chiarini S Barbiero VS mRydel RE Racagni G Popoli M Long-term soluble Abeta1-40 activates CaM kinase II in organotypic hippocampal cultures Neurobiol Aging 2007 28 1388 1395 16846668
- Thomas A Kim DS Fields RL Chin H Gainer H Quantitative analysis of gene expression in organotypic slice-explant cultures by particle-mediated gene transfer J Neurosci Methods 1998 84 181 191 9821650
- Timpe JM Wang CZ Kim J Johnson KM Alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor activation protects against phencyclidine-induced caspase-3 activity by activating voltage-gated calcium channels J Neurosci Res 2014 92 12 1785 1791 24995437
- Ullrich C Humpel C The pro-apoptotic substance thapsigargin selectively stimulates re-growth of brain capillaries Curr Neurovasc Res 2009a 6 171 180 19534719 PMC4311392
- Ullrich C Humpel C Rotenone induces cell death of cholinergic neurons in an organotypic co-culture brain slice model Neurochem Res 2009b 34 2147 2153 19495971 PMC4311144
- Ullrich C Humpel C Mini-ruby is rapidly taken up by neurons and astrocytes in organotypic brain slices Neurochem Res 2011 36 1817 1823 21604155 PMC4311056
- Ullrich C Daschil N Humpel C Organotypic vibrosections: novel whole sagittal brain cultures J Neurosci Methods 2011 201 131 141 21835204 PMC3176904
- Victorov IV Lyjin AA Aleksandrova OP A modified roller method for organotypic brain cultures: free-floating slices of postnatal rat hippocampus Brain Res Brain Res Protoc 2001 7 30 37 11275521
- Weis C Marksteiner J Humpel C Nerve growth factor and glial cell line-derived neurotrophic factor restore the cholinergic phenotype in organotypic brain slices of the basal nucleus of Meynert Neuroscience 2001 102 129 138 11226676
- Whetsell WO Jr Mytilineou C Shen J Yahr MD The development of the dog nigrostriatal system in organotypic culture J Neural Transm 1981 52 149 161 7310391
- Wilhelmi E Schöder UH Benabdallah A Sieg F Breder J Reymann KG Organotypic brain-slice cultures from adult rats: approaches for a prolonged culture time Altern Lab Anim 2002 30 275 283 12106005
- Wolf MK Anatomy of cultured mouse cerebellum. II. Organotypic migration of granule cells demonstrated by silver impregnation of normal and mutant cultures J Comp Neurol 1970 140 281 298 4097714
- Wolff JR Goerz C Bär T Güldner FH Common morphogenetic aspects of various organotypic microvascular patterns Microvasc Res 1975 10 373 395 1214601
- Woodhams PL Atkinson DJ Regeneration of entorhino-dentate projections in organotypic slice cultures: mode of axonal regrowth and effects of growth factors Exp Neurol 1996 140 68 78 8682181
- Wray S Castel M Gainer H Characterization of the suprachiasmatic nucleus in organotypic slice explant cultures Microsc Res Tech 1993 25 46 60 8353307
- Xu B Wang F Wu SW Deng Y Liu W Feng S Yang TY Xu ZF Alpha-synuclein is involved in manganese-induced ER stress via PERK signal pathway in organotypic brain slice cultures Mol Neurobiol 2014 49 1 399 412 23934647
- Zassler B Weis C Humpel C Tumor necrosis factor-alpha triggers cell death of sensitized potassium chloride-stimulated cholinergic neurons Mol Brain Res 2003 113 78 85 12750009
- Zassler B Dechant G Humpel C Urea enhances the nerve growth factor-induced neuroprotective effect on cholinergic neurons in organotypic rat brain slices Neuroscience 2005 130 317 323 15664688
- Zehendner CM Wedler HE Luhmann HJ A novel in vitro model to study pericytes in the neurovascular unit of the developing cortex PLoS One 2013 8 e81637 24278454 PMC3836850
- Zhabotinski YM Chumasov EI Chubakov AR Konovalov HV Development of synaptic structure and function in organotypic cultures of the rat hippocampus Neuroscience 1979 4 913 920 552612
- Zimmer J Gähwiler BH Cellular and connective organization of slice cultures of the rat hippocampus and fascia dentata J Comp Neurol 1984 228 432 446 6148364
- Zimmer J Gähwiler BH Growth of hippocampal mossy fibers: a lesion and coculture study of organotypic slice cultures J Comp Neurol 1987 264 1 13 2445790
Cited by
Sorted by citations
Gulino, M., Kim, D., Pané, S., Santos, S. D., & Pêgo, A. P. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00689 · Cited by 159 · see citing works
Multiplexed drug testing of tumor slices using a microfluidic platform
Horowitz, L. F., Rodriguez, A. D., Dereli-Korkut, Z., Lin, R., Castro, K., Mikheev, A. M., Monnat, R. J., Folch, A., & Rostomily, R. C. (2020) · npj Precision Oncology · doi:10.1038/s41698-020-0117-y · Cited by 88 · see citing works
Davis, N., Mota, B. C., Stead, L., Palmer, E. O. C., Lombardero, L., Rodríguez-Puertas, R., de Paola, V., Barnes, S. J., & Sastre, M. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02117-y · Cited by 65 · see citing works
Saliba, S. W., Marcotegui, A. R., Fortwängler, E., Ditrich, J., Perazzo, J. C., Muñoz, E., de Oliveira, A. C. P., & Fiebich, B. L. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-1014-3 · Cited by 62 · see citing works
Organotypic cultures as aging associated disease models
Sanchez, M. M., Bagdasarian, I. A., Darch, W., & Morgan, J. T. (2022) · Aging · doi:10.18632/aging.204361 · Cited by 12 · see citing works
Kennedy, L., Morland, C., Narum, M., Bergersen, L. H., & Rinholm, J. E. (2025) · eneuro · doi:10.1523/eneuro.0563-24.2025 · Cited by 8 · see citing works
An Overview of Multiple Sclerosis In Vitro Models
Czpakowska, J., Kałuża, M., Szpakowski, P., & Głąbiński, A. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25147759 · Cited by 7 · see citing works
Vaglio-Garro, A., Theuermann, M., Sweis, K. E., Zavadskis, S., Kokas, M., Környei, Z., Karas, M., Tretter, L., Komlódi, T., Weidinger, A., et al. (2026) · eneuro · doi:10.1523/eneuro.0439-25.2026
- Authors
- Humpel, C.
- Affiliations
- Innsbruck Medical University (AT)
- Corresponding author
- Humpel, C.
- ORCID
- Humpel, C.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2015-10
- Volume
- 305
- Pages
- 86-98
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC4699268
- OpenAlex
- W1112818150
- Cited by
- 480
- References
- 4
- Citations by year
- 2026: 38 · 2025: 54 · 2024: 46 · 2023: 56 · 2022: 50 · 2021: 50 · 2020: 52 · 2019: 37 · 2018: 40 · 2017: 41 · 2016: 14 · 2015: 2
- FWCI
- 3.84
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Neuroscience (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Austrian Science Fund (P24734-B24)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- organotypic brain slice culture, membrane technology, donor age, culture media, cholinergic neurons, Alzheimer's disease, neurodegeneration model, nigrostriatal dopaminergic neurons, Parkinson's disease, blood-brain barrier, cerebral vasculature
- MeSH terms
- Animals, Brain, Organ Culture Techniques, Dopaminergic Neurons, Cholinergic Neurons, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review