Restricted accessReview articleFirst published online 2025-7
Bridging the gap: Canine in vitro models of the central nervous system as tools to study pathogenetic mechanisms in neurodegenerative disease and neuroinfectiology
The increasing implementation of the 3R principles of reduce, replace, and refine, as well as costs and ethical considerations associated with animal experiments, will lead to an incremental reduction in in vivo experimentation. To fill the gap between in vitro generated data and findings obtained following in vivo animal experiments, there is an urgent need for reliable and robust in vitro models with high comparability to the respective in vivo situation. This applies in particular for models of the central nervous system (CNS) due its unique anatomical and physiological characteristics with the resulting limited accessibility for diagnostic and therapeutic approaches and, simultaneously, the devastating consequences of CNS diseases. Sophisticated in vitro canine models will contribute to progression in veterinary medicine and are uniquely suited to study a broad range of human diseases, including monogenic hereditary illnesses, cancers, degenerative and inflammatory diseases, and epilepsy. In addition, notable neurotropic or pantropic pathogens such as rabies virus, canine distemper virus, canine herpesvirus, Toxoplasma sp., and tick-borne encephalitis, as well as previously unknown emerging pathogens, can be studied directly, providing much needed information about cell tropism, pathogen spread, and underlying mechanisms. This review summarizes established canine 2-dimensional and 3-dimensional in vitro models of the CNS including traditional monoculture and coculture systems as well as more advanced systems such as neurospheres, organoids, and organotypic brain slice cultures. The aim is to assess their suitability, current state, and potential applications, as well as challenges and limitations with special focus on neurodegenerative and neuroinfectious diseases.
AbugomaaAElbadawyMYamamotoH, et al. Establishment of a direct 2.5D organoid culture model using companion animal cancer tissues. Biomed Pharmacother. 2022;154:113597.
2.
AccardiMVHuangHAuthierS.Seizure liability assessments using the hippocampal tissue slice: comparison of non-clinical species. J Pharmacol Toxicol Methods. 2018;93:59–68.
3.
AcharyaPChoiNYShresthaS, et al. Brain organoids: a revolutionary tool for modeling neurological disorders and development of therapeutics. Biotechnol Bioeng. 2024;121:489–506.
4.
AclandGMAguirreGDRayJ, et al. Gene therapy restores vision in a canine model of childhood blindness. Nature Genetics. 2001;28:92–95.
5.
AfanasyevaTAVCorral-SerranoJCGarantoA, et al. A look into retinal organoids: methods, analytical techniques, and applications. Cell Mol Life Sci. 2021;78:6505–6532.
6.
AfecheSCde Piazza PimentelDFerroLF, et al. Pineal cells dissociation and culture: isolated pinealocytes, isolated astrocytes, and co-culture. Methods Mol Biol. 2022;2550:85–94.
7.
AguirreGDBaldwinVPearce-KellingS, et al. Congenital stationary night blindness in the dog: common mutation in the RPE65 gene indicates founder effect. Mol Vis. 1998;4:23.
8.
AlbanitoLReddyCEMustiAM.C-Jun is essential for the induction of Il-1β gene expression in in vitro activated Bergmann glial cells. Glia. 2011;59:1879–1890.
9.
AlcockJScottingPSottileV.Bergmann glia as putative stem cells of the mature cerebellum. Medical Hypotheses. 2007;69:341–345.
10.
AlcockJSottileV.Dynamic distribution and stem cell characteristics of Sox1-expressing cells in the cerebellar cortex. Cell Res. 2009;19:1324–1333.
11.
AllenCOpyrchalMAdercaI, et al. Oncolytic measles virus strains have significant antitumor activity against glioma stem cells. Gene Ther. 2013;20:444–449.
12.
AllenspachKZavrosYElbadawyM, et al. Leveraging the predictive power of 3D organoids in dogs to develop new treatments for man and man’s best friend. BMC Biol. 2023;21:297.
13.
AlvesLKhosraviMAvilaM, et al. SLAM- and nectin-4-independent noncytolytic spread of canine distemper virus in astrocytes. J Virol. 2015;89:5724–5733.
14.
AmosPJCagavi BozkulakEQyangY.Methods of cell purification: a critical juncture for laboratory research and translational science. Cells Tissues Organs. 2012;195:26–40.
15.
AnnearMJMowatFMOccelliLM, et al. A comprehensive study of the retinal phenotype of Rpe65-deficient dogs. Cells. 2021;10:115.
16.
AoZCaiHWuZ, et al. Tubular human brain organoids to model microglia-mediated neuroinflammation. Lab Chip. 2021;21:2751–2762.
17.
AriffIMThounaojamMCDasS, et al. Japanese encephalitis virus infection alters both neuronal and astrocytic differentiation of neural stem/progenitor cells. J Neuroimmune Pharmacol. 2013;8:664–676.
18.
ArnholdSWenischS.Adipose tissue derived mesenchymal stem cells for musculoskeletal repair in veterinary medicine. Am J Stem Cells. 2015;4:1–12.
19.
AssinckPDuncanGJHiltonBJ, et al. Cell transplantation therapy for spinal cord injury. Nat Neurosci. 2017;20:637–647.
20.
AugustyniakJBerteroACocciniT, et al. Organoids are promising tools for species-specific in vitro toxicological studies. J Appl Toxicol. 2019;39:1610–1622.
21.
AwadHSuntresZHeijmansJ, et al. Intracellular and extracellular expression of the major inducible 70kDa heat shock protein in experimental ischemia-reperfusion injury of the spinal cord. Exp Neurol. 2008;212:275–284.
22.
BaileyJPereiraS.Advances in neuroscience imply that harmful experiments in dogs are unethical. J Med Ethics. 2018;44:47–52.
BaneuxPMartinMAllenM, et al. Issues related to institutional animal care and use committees and clinical trials using privately owned animals. ILAR J. 2014;55:200–209.
25.
Barnabé-HeiderFGöritzCSabelströmH, et al. Origin of new glial cells in intact and injured adult spinal cord. Cell Stem Cell. 2010;7:470–482.
26.
BarnesKLKnowlesWDFerrarioCM.Angiotensin II and angiotensin (1-7) excite neurons in the canine medulla in vitro. Brain Res Bull. 1990;24:275–280.
27.
BarnesKLKnowlesWDFerrarioCM.Neuronal responses to angiotensin II in the in vitro slice from the canine medulla. Hypertension. 1988;11:680–684.
28.
BarrachinaLArshaghiTEO’BrienA, et al. Induced pluripotent stem cells in companion animals: how can we move the field forward?Front Vet Sci. 2023;10:1176772.
29.
BartonSAKentMHechtEE.Neuroanatomical asymmetry in the canine brain. Brain Struct Funct. 2023;228:1657–1669.
30.
BeckerKCanaABaumgärtnerW, et al. P75 neurotrophin receptor: a double-edged sword in pathology and regeneration of the central nervous system. Vet Pathol. 2018;55:786–801.
31.
BedosLWickhamHGabrielV, et al. Culture and characterization of canine and feline corneal epithelial organoids: a new tool for the study and treatment of corneal diseases. Front Vet Sci. 2022;9:1050467.
32.
BeinekeAPuffCSeehusenF, et al. Pathogenesis and immunopathology of systemic and nervous canine distemper. Vet Immunol Immunopathol. 2009;127:1–18.
33.
BellapiantaACetkovicABolzM, et al. Retinal organoids and retinal prostheses: an overview. Int J Mol Sci. 2022;23:2922.
34.
BeltranWA.The use of canine models of inherited retinal degeneration to test novel therapeutic approaches. Vet Ophthalmol. 2009;12:192–204.
35.
BerensMEBjotvedtGLevesqueDC, et al. Tumorigenic, invasive, karyotypic, and immunocytochemical characteristics of clonal cell lines derived from a spontaneous canine anaplastic astrocytoma. In Vitro Cell Dev Biol Anim. 1993;29a:310–318.
36.
BerensMEGieseAShapiroJR, et al. Allogeneic astrocytoma in immune competent dogs. Neoplasia. 1999;1:107–112.
37.
BettsDHTobiasIC.Canine pluripotent stem cells: are they ready for clinical applications?Front Vet Sci. 2015;2:41.
38.
BleckerDElashryMIHeimannM, et al. New insights into the neural differentiation potential of canine adipose tissue-derived mesenchymal stem cells. Anat Histol Embryol. 2017;46:304–315.
39.
BochMHuberLLammC.Domestic dogs as a comparative model for social neuroscience: advances and challenges. Neurosci Biobehav Rev. 2024;162:105700.
40.
BockPBeinekeATechangamsuwanS, et al. Differential expression of HNK-1 and p75(NTR) in adult canine Schwann cells and olfactory ensheathing cells in situ but not in vitro. J Comp Neurol. 2007;505:572–585.
41.
BockPSpitzbarthIHaistV, et al. Spatio-temporal development of axonopathy in canine intervertebral disc disease as a translational large animal model for nonexperimental spinal cord injury. Brain Pathol. 2013;23:82–99.
42.
BotteronCZurbriggenAGriotC, et al. Canine distemper virus-immune complexes induce bystander degeneration of oligodendrocytes. Acta Neuropathol. 1992;83:402–407.
43.
BoudreauCEYorkDHigginsRJ, et al. Molecular signalling pathways in canine gliomas. Vet Comp Oncol. 2017;15:133–150.
44.
BranscomeHKhatkarPAl SharifS, et al. Retroviral infection of human neurospheres and use of stem Cell EVs to repair cellular damage. Scientific Reports. 2022;12:2019.
45.
BrewerGJTorricelliJR.Isolation and culture of adult neurons and neurospheres. Nature Protocols. 2007;2:1490–1498.
46.
BürgeTGriotCVandeveldeM, et al. Antiviral antibodies stimulate production of reactive oxygen species in cultured canine brain cells infected with canine distemper virus. J Virol. 1989;63:2790–2797.
47.
Buzoianu-AnguianoVTorres-LlacsaMDoncel-PérezE.Role of aldynoglia cells in neuroinflammatory and neuroimmune responses after spinal cord injury. Cells. 2021;10:2783.
48.
CakirBKiralFRParkIH.Advanced in vitro models: microglia in action. Neuron. 2022;110:3444–3457.
CartiauxBDeviersADelmasC, et al. Evaluation of in vitro intrinsic radiosensitivity and characterization of five canine high-grade glioma cell lines. Front Vet Sci. 2023;10:1253074.
CashaSYuWRFehlingsMG.FAS deficiency reduces apoptosis, spares axons and improves function after spinal cord injury. Exp Neurol. 2005;196:390–400.
53.
CekanovaMRathoreK.Animal models and therapeutic molecular targets of cancer: utility and limitations. Drug Des Devel Ther. 2014;8:1911–1921.
54.
ChandrasekaranAThomsenBBAgerholmJS, et al. Neural derivates of canine induced pluripotent stem cells-like cells from a mild cognitive impairment dog. Front Vet Sci. 2021;8:725386.
ChenYBalasubramaniyanVPengJ, et al. Isolation and culture of rat and mouse oligodendrocyte precursor cells. Nat Protoc. 2007;2:1044–1051.
57.
ChenYTTanKAPangLY, et al. The class I PI3K/Akt pathway is critical for cancer cell survival in dogs and offers an opportunity for therapeutic intervention. BMC Vet Res. 2012;8:73.
58.
ChenZYZhangY.Animal models of Alzheimer’s disease: applications, evaluation, and perspectives. Zool Res. 2022;43:1026–1040.
59.
ChhibberTBagchiSLahootiB, et al. CNS organoids: an innovative tool for neurological disease modeling and drug neurotoxicity screening. Drug Discov Today. 2020;25:456–465.
60.
ChowLJohnsonVReganD, et al. Safety and immune regulatory properties of canine induced pluripotent stem cell-derived mesenchymal stem cells. Stem Cell Res. 2017;25:221–232.
61.
ChowLMcGrathSde Arruda SaldanhaC, et al. Generation of neural progenitor cells from canine induced pluripotent stem cells and preliminary safety test in dogs with spontaneous spinal cord injuries. Front Vet Sci. 2020;7:575938.
62.
ChuahMIAuC.Cultures of ensheathing cells from neonatal rat olfactory bulbs. Brain Res. 1993;601:213–220.
63.
ChungCSFujitaNKawaharaN, et al. A comparison of neurosphere differentiation potential of canine bone marrow-derived mesenchymal stem cells and adipose-derived mesenchymal stem cells. J Vet Med Sci. 2013;75:879–886.
64.
ChungDJWongAHayashiK, et al. Effect of hypoxia on generation of neurospheres from adipose tissue-derived canine mesenchymal stromal cells. Vet J. 2014;199:123–130.
65.
Cislo-PakulukASmieszekAKucharczykN, et al. Intra-vitreal administration of microvesicles derived from human adipose-derived multipotent stromal cells improves retinal functionality in dogs with retinal degeneration. J Clin Med. 2019;8:510.
66.
Cisneros CastilloLROanceaA-DStülleinC, et al. Evaluation of consistency in spheroid invasion assays. Sci Rep. 2016;6:28375.
67.
CoatesJRWiningerFA.Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. 2010;40:929–950.
68.
ContardoMDe GioiaRGagliardiD, et al. Targeting PTB for Glia-to-neuron reprogramming In Vitro and In Vivo for therapeutic development in neurological diseases. Biomedicines. 2022;10:399.
69.
CroftCLFutchHSMooreBD, et al. Organotypic brain slice cultures to model neurodegenerative proteinopathies. Mol Neurodegener. 2019;14:45.
70.
da HoraCCSchweigerMWWurdingerT, et al. Patient-derived glioma models: from patients to dish to animals. Cells. 2019;8:1177.
71.
da Silva SiqueiraLMajoloFda SilvaAPB, et al. Neurospheres: a potential in vitro model for the study of central nervous system disorders. Mol Biol Rep. 2021;48:3649–3663.
72.
DaliREstrada-MezaJLangletF.Tanycyte, the neuron whisperer. Physiol Behav. 2023;263:114108.
73.
DasSBasuA.Japanese encephalitis virus infects neural progenitor cells and decreases their proliferation. J Neurochem. 2008;106:1624–1636.
de Lima CavalcantiTYVLimaMCBargi-SouzaP, et al. Zika virus infection alters the circadian clock expression in human neuronal monolayer and neurosphere cultures. Cell Mol Neurobiol. 2023;44:10.
76.
DebinskiWDickinsonPRossmeislJH, et al. New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors. PLoS ONE. 2013;8:e77719.
77.
DedoniSSchermaMCamoglioC, et al. An overall view of the most common experimental models for multiple sclerosis. Neurobiol Dis. 2023;184:106230.
78.
DeweyCWDaviesESXieH, et al. Canine cognitive dysfunction: pathophysiology, diagnosis, and treatment. Vet Clin North Am Small Anim Pract. 2019;49:477–499.
79.
DíazLZambranoEFloresME, et al. Ethical considerations in animal research: the principle of 3R’s. Rev Invest Clin. 2020;73:199–209.
80.
DionneKRGalvinJMSchittoneSA, et al. Type I interferon signaling limits reoviral tropism within the brain and prevents lethal systemic infection. J Neurovirol. 2011;17:314–326.
81.
DromardCGuillonHRigauV, et al. Adult human spinal cord harbors neural precursor cells that generate neurons and glial cells in vitro. J Neurosci Res. 2008;86:1916–1926.
82.
DuncanTLoweADaltonMA, et al. Isolation and expansion of adult canine hippocampal neural precursors. J Vis Exp. 2016;29:54953.
83.
DuvalKGroverHHanLH, et al. Modeling physiological events in 2Dvs. 3D cell culture. Physiology (Bethesda).2017;32:266–277.
84.
EdamakantiCRMohanVOpalP.Reactive Bergmann glia play a central role in spinocerebellar ataxia inflammation via the JNK pathway. J Neuroinflammation. 2023;20:126.
85.
EdamuraKKuriyamaKKatoK, et al. Proliferation capacity, neuronal differentiation potency and microstructures after the differentiation of canine bone marrow stromal cells into neurons. J Vet Med Sci. 2012;74:923–927.
86.
EirakuMTakataNIshibashiH, et al. Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature. 2011;472:51–56.
87.
EisemannTCostaBStrelauJ, et al. An advanced glioma cell invasion assay based on organotypic brain slice cultures. BMC Cancer. 2018;18:103.
88.
EmplMTMackeSWinterhalterP, et al. The growth of the canine glioblastoma cell line D-GBM and the canine histiocytic sarcoma cell line DH82 is inhibited by the resveratrol oligomers hopeaphenol and r2-viniferin. Vet Comp Oncol. 2014;12:149–159.
89.
EnsingerEMBoekhoffTMCarlsonR, et al. Regional topographical differences of canine microglial immunophenotype and function in the healthy spinal cord. J Neuroimmunol. 2010;227:144–152.
90.
EugèneECluzeaudFCifuentes-DiazC, et al. An organotypic brain slice preparation from adult patients with temporal lobe epilepsy. J Neurosci Methods. 2014;235:234–244.
91.
FanWChristianKMSongH, et al. Applications of brain organoids for infectious diseases. J Mol Biol. 2022;434:167243.
92.
FeiZQXiongJYChenL, et al. Differentiation of human bone marrow precursor cells into neuronal-like cells after transplantation into canine spinal cord organotypic slice cultures. Chin Med J (Engl). 2012;125:4049–4054.
93.
Fernández-FloresFGarcía-VerdugoJMMartín -IbáñezR, et al. Characterization of the canine rostral ventricular-subventricular zone: morphological, immunohistochemical, ultrastructural, and neurosphere assay studies. J Comp Neurol. 2018;526:721–741.
94.
FerrenMLalandeAIampietroM, et al. Early permissiveness of central nervous system cells to measles virus infection is determined by hyperfusogenicity and interferon pressure. Viruses. 2023;15:229.
95.
FinstererJAuerH.Neurotoxocarosis. Rev Inst Med Trop Sao Paulo. 2007;49:279–287.
96.
FluehmannGDoherrMGJaggyA.Canine neurological diseases in a referral hospital population between 1989;and 2000 in Switzerland. J Small Anim Pract. 2006;47:582–587.
97.
FordALGoodsallALHickeyWF, et al. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic Differences Defined and Direct Ex Vivo Antigen Presentation to Myelin Basic Protein-reactive CD4+ T Cells Compared. J Immunol. 1995;154:4309–4321.
98.
FortunaPRJBielefeldt-OhmannHOvchinnikovDA, et al. Cortical neurons derived from equine induced pluripotent stem cells are susceptible to neurotropic flavivirus infection and replication: an in vitro model for equine neuropathic diseases. Stem Cells Dev. 2018;27:704–715.
99.
FriedlGHoferMAuberB, et al. Borna disease virus multiplication in mouse organotypic slice cultures is site-specifically inhibited by gamma interferon but not by interleukin-12. J Virol. 2004;78:1212–1218.
100.
GadauS.Setting up of primary cultures from fetal dog brain: an alternative method in line with the 3Rs principles. Austin Biology. 2016;1:1–5.
101.
GaubBMBerryMHHoltAE, et al. Restoration of visual function by expression of a light-gated mammalian ion channel in retinal ganglion cells or ON-bipolar cells. Proc Natl Acad Sci U S A. 2014;111:E5574–E5583.
102.
GeniniSBeltranWASteinVM, et al. Isolation and ex vivo characterization of the immunophenotype and function of microglia/macrophage populations in normal dog retina. Adv Exp Med Biol. 2014;801:339–345.
103.
GhoreishianMRezaeiMBeniBH, et al. Facial nerve repair with Gore-Tex tube and adipose-derived stem cells: an animal study in dogs. J Oral Maxillofac Surg. 2013;71:577–587.
104.
GitlinJDD’AmorePA.Culture of retinal capillary cells using selective growth media. Microvasc Res. 1983;26:74–80.
105.
GnanadesikanGEHareBSnyder-MacklerN, et al. Breed differences in dog cognition associated with brain-expressed genes and neurological functions. Integr Comp Biol. 2020;60:976–990.
106.
Gómez-FloresAIChávez-LópezJJVillatoro-ChacónDM.Caracterización de enfermedades neurológicas en caninos: Universidad de San Carlos de Guatemala, año 2017. Revista MVZ Córdoba. 2021;26:e2047.
107.
GonçalvesNJNBressanFFRoballoKCS, et al. Generation of LIF-independent induced pluripotent stem cells from canine fetal fibroblasts. Theriogenology. 2017;92:75–82.
108.
GraberHUMüllerCFVandeveldeM, et al. Restricted infection with canine distemper virus leads to down-regulation of myelin gene transcription in cultured oligodendrocytes. Acta Neuropathol. 1995;90:312–318.
109.
GrabiecUHohmannTHammerN, et al. Organotypic hippocampal slice cultures as a model to study neuroprotection and invasiveness of tumor cells. J Vis Exp. 2017;126:55359.
110.
GuS-MThompsonDASrikumariCRS, et al. Mutations in RPE65 cause autosomal recessive childhood–onset severe retinal dystrophy. Nature Genetics. 1997;17:194–197.
111.
HansmannFJungwirthNZhangN, et al. Beneficial and detrimental impact of transplanted canine adipose-derived stem cells in a virus-induced demyelinating mouse model. Vet Immunol Immunopathol. 2018;202:130–140.
112.
HardeboJEOwmanCH.Characterization of the in vitro uptake of monoamines into brain microvessels. Acta Physiologica Scandinavica. 1980;108:223–229.
113.
HatoyaSToriiRKondoY, et al. Isolation and characterization of embryonic stem-like cells from canine blastocysts. Mol Reprod Dev. 2006;73:298–305.
114.
HattenME.Embryonic cerebellar astroglia in vitro. Brain Res. 1984;13:309–313.
115.
HatzCFKuenzliEFunkM.Rabies: relevance, prevention, and management in travel medicine. Infect Dis Clin North Am. 2012;26:739–753.
116.
HayakawaHHayashita-KinohHNihiraT, et al. The isolation of neural stem cells from the olfactory bulb of Parkinson’s disease model. Neurosci Res. 2007;57:393–398.
117.
HayesBFagerlieSRRamakrishnanA, et al. Derivation, characterization, and in vitro differentiation of canine embryonic stem cells. Stem Cells. 2008;26:465–473.
118.
HechtEESmaersJBDunnWD, et al. Significant neuroanatomical variation among domestic dog breeds. J Neurosci. 2019;39:7748–7758.
119.
HeimrichBFrotscherM.Slice cultures as a model to study entorhinal-hippocampal interaction. Hippocampus. 1993;3 Spec No:11–17.
120.
HiramatsuSMorizaneAKikuchiT, et al. Cryopreservation of induced pluripotent stem cell-derived dopaminergic neurospheres for clinical application. J Parkinsons Dis. 2022;12:871–884.
121.
HoffmanKLDuncanID.Canine oligodendrocytes undergo morphological changes in response to basic fibroblast growth factor (bFGF) in vitro. Glia. 1995;14:33–42.
122.
HogbergHTBresslerJChristianKM, et al. Toward a 3D model of human brain development for studying gene/environment interactions. Stem Cell Res Ther. 2013;4:S4.
123.
HopkinsAMDeSimoneEChwalekK, et al. 3D in vitro modeling of the central nervous system. Prog Neurobiol. 2015;125:1–25.
124.
HülsmeyerV-IFischerAMandigersPJJ, et al. International veterinary epilepsy Task Force’s current understanding of idiopathic epilepsy of genetic or suspected genetic origin in purebred dogs. BMC Vet Res. 2015;11:175.
125.
HumpelC.Organotypic brain slice cultures: a review. Neuroscience. 2015;305:86–98.
126.
HumpelC.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.
127.
HurtKJFiskumGRosenthalRE, et al. The role of L-type voltage dependent calcium channels in stimulated [3H]norepinephrine release from canine hippocampal slices following global cerebral ischemia and reperfusion. Brain Res. 1995;673:226–232.
128.
HuuskonenJSuuronenTMiettinenR, et al. A refined in vitro model to study inflammatory responses in organotypic membrane culture of postnatal rat hippocampal slices. J Neuroinflammation. 2005;2:25.
129.
HytönenMKLohiH.Canine models of human rare disorders. Rare Dis. 2016;4:e1241362.
130.
ImbschweilerISeehusenFPeckCT, et al. Increased p75 neurotrophin receptor expression in the canine distemper virus model of multiple sclerosis identifies aldynoglial Schwann cells that emerge in response to axonal damage. Glia. 2012;60:358–371.
131.
ItoDIbanezCOgawaH, et al. Comparison of cell populations derived from canine olfactory bulb and olfactory mucosal cultures. Am J Vet Res. 2006;67:1050–1056.
132.
JaggyACouteurR.Atlas and Textbook of Small Animal Neurology: An Illustrated Text. Hanover: Schluetersche; 2010.
133.
JangSChoH-HChoY-B, et al. Functional neural differentiation of human adipose tissue-derived stem cells using bFGF and forskolin. BMC Cell Bio. 2010;11:25.
134.
JefferyNDLakatosAFranklinRJ.Autologous olfactory glial cell transplantation is reliable and safe in naturally occurring canine spinal cord injury. J Neurotrauma. 2005;22:1282–1293.
135.
JensenJBParmarM.Strengths and limitations of the neurosphere culture system. Mol Neurobiol. 2006;34:153–161.
136.
JohanssonCBMommaSClarkeDL, et al. Identification of a neural stem cell in the adult mammalian central nervous system. Cell. 1999;96:25–34.
137.
JohnsonGRKoestnerAKindigO, et al. Effects of a pathogenic canine herpesvirus on canine brain cell cultures and cerebellar explants. Acta Neuropathol. 1970;15:97–113.
138.
JosupeitRBenderSKernS, et al. Pediatric and adult high-grade glioma stem cell culture models are permissive to lytic infection with parvovirus H-1. Viruses. 2016;8:138.
139.
JungwirthNSalinas TejedorLJinW, et al. Mesenchymal stem cells form 3D clusters following intraventricular transplantation. J Mol Neurosci. 2018;65:60–73.
140.
KaidCGoulartECaires-JúniorLC, et al. Zika virus selectively kills aggressive human embryonal CNS tumor cells in vitro and in vivo. Cancer Res. 2018;78:3363–3374.
141.
KamishinaHCheesemanJAClemmonsRM.Nestin-positive spheres derived from canine bone marrow stromal cells generate cells with early neuronal and glial phenotypic characteristics. In Vitro Cell Dev Biol Anim. 2008;44:140–144.
142.
KaurGDufourJM.Cell lines: valuable tools or useless artifacts. Spermatogenesis. 2012;2:1–5.
143.
KeglerKSpitzbarthIImbschweilerI, et al. Contribution of Schwann cells to remyelination in a naturally occurring canine model of CNS neuroinflammation. PLoS ONE. 2015;10:e0133916.
144.
KhairullahARKurniawanSCHasibA, et al. Tracking lethal threat: in-depth review of rabies. Open Vet J. 2023;13:1385–1399.
145.
KijasJWCideciyanAVAlemanTS, et al. Naturally occurring rhodopsin mutation in the dog causes retinal dysfunction and degeneration mimicking human dominant retinitis pigmentosa. Proc Natl Acad Sci U S A. 2002;99:6328–6333.
146.
KijasJWMillerBJPearce-KellingSE, et al. Canine models of ocular disease: outcross breedings define a dominant disorder present in the English mastiff and bull mastiff dog breeds. J Hered. 2003;94:27–30.
147.
KimHKimEParkM, et al. Organotypic hippocampal slice culture from the adult mouse brain: a versatile tool for translational neuropsychopharmacology. Prog Neuropsychopharmacol Biol Psychiatry. 2013;41:36–43.
148.
KimMHwangSUYoonJD, et al. Optimized approaches for the induction of putative canine induced pluripotent stem cells from old fibroblasts using synthetic RNAs. Animals (Basel). 2020;10:1848.
149.
KimWKSonYSLimJH, et al. Neural stem/progenitor cells from adult canine cervical spinal cord have the potential to differentiate into neural lineage cells. BMC Vet Res. 2023;19:193.
150.
KimuraKTsukamotoMTanakaM, et al. Efficient reprogramming of canine peripheral blood mononuclear cells into induced pluripotent stem cells. Stem Cells Dev. 2021;30:79–90.
151.
KimuraKTsukamotoMYoshidaT, et al. Canine induced pluripotent stem cell maintenance under feeder-free and chemically-defined conditions. Mol Reprod Dev. 2021;88:395–404.
152.
KoehlerJSandeyMPrasadN, et al. Differential expression of miRNAs in hypoxia (“HypoxamiRs”) in three canine high-grade glioma cell lines. Front Vet Sci. 2020;7:104.
153.
KohSThomasRTsaiS, et al. Growth requirements and chromosomal instability of induced pluripotent stem cells generated from adult canine fibroblasts. Stem Cells Dev. 2012;22:951–963.
154.
KordeDSHumpelC.A combination of heavy metals and intracellular pathway modulators induces Alzheimer disease-like pathologies in organotypic brain slices. Biomolecules. 2024;14:165.
155.
KovácsKKisAPogány KollerÁD, et al. Differential effects of oxytocin on social sensitivity in two distinct breeds of dogs (Canis familiaris). Psychoneuroendocrinology. 2016;74:212–220.
156.
KrudewigCDeschlUWewetzerK.Purification and in vitro characterization of adult canine olfactory ensheathing cells. Cell Tissue Res. 2006;326:687–696.
157.
KuriharaYSuzukiTSakaueM, et al. Valproic acid, a histone deacetylase inhibitor, decreases proliferation of and induces specific neurogenic differentiation of canine adipose tissue-derived stem cells. J Vet Med Sci. 2014;76:15–23.
158.
KuwamuraMHattoriRYamateJ, et al. Neuronal ceroid-lipofuscinosis and hydrocephalus in a chihuahua. J Small Anim Pract. 2003;44:227–230.
159.
Kuzma-HuntAGShahVDiMarcoS, et al. Opening the “Black Box” underlying barriers to the use of canine induced pluripotent stem cells: a narrative review. Stem Cells Dev. 2023;32:271–291.
160.
KyöstiläKCizinauskasSSeppäläEH, et al. A SEL1L mutation links a canine progressive early-onset cerebellar ataxia to the endoplasmic reticulum-associated protein degradation (ERAD) machinery. PLoS Genet. 2012;8:e1002759.
161.
LaiSRCastelloSARobinsonAC, et al. In vitro anti-tubulin effects of mebendazole and fenbendazole on canine glioma cells. Vet Comp Oncol. 2017;15:1445–1454.
162.
LaksonoBMTranDNKondovaI, et al. Comparable infection level and tropism of measles virus and canine distemper virus in organotypic brain slice cultures obtained from natural host species. Viruses. 2021;13:1582.
163.
LancasterMARennerMMartinCA, et al. Cerebral organoids model human brain development and microcephaly. Nature. 2013;501:373–379.
164.
LangmannT.Microglia activation in retinal degeneration. J Leukoc Biol. 2007;81:1345–1351.
165.
LeeASXuDPlewsJR, et al. Preclinical derivation and imaging of autologously transplanted canine induced pluripotent stem cells*. J Biol Chem. 2011;286:32697–32704.
166.
LeeJKotliarovaSKotliarovY, et al. Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines. Cancer Cell. 2006;9:391–403.
167.
LemppCSpitzbarthIPuffC, et al. New aspects of the pathogenesis of canine distemper leukoencephalitis. Viruses. 2014;6:2571–2601.
168.
LewchalermwongP.The occurrence of neurological disorders in companion animals during 2012–2013, Bangkok, Thailand. In: The 40th Congress of the World Small Animal Veterinary Association; May2015; Bangkok, Thailand.
169.
LiAWallingJKotliarovY, et al. Genomic changes and gene expression profiles reveal that established glioma cell lines are poorly representative of primary human gliomas. Mol Cancer Res. 2008;6:21–30.
170.
LiangSZhouJYuX, et al. Neuronal conversion from glia to replenish the lost neurons. Neural Regen Res. 2024;19:1446–1453.
171.
LimJHBoozerLMarianiCL, et al. Generation and characterization of neurospheres from canine adipose tissue-derived stromal cells. Cell Reprogram. 2010;12:417–425.
172.
LimJHByeonYERyuHH, et al. Transplantation of canine umbilical cord blood-derived mesenchymal stem cells in experimentally induced spinal cord injured dogs. J Vet Sci. 2007;8:275–282.
173.
LimJHKohSOlbyNJ, et al. Isolation and characterization of neural progenitor cells from adult canine brains. Am J Vet Res. 2012;73:1963–1968.
174.
LimJHKohSThomasR, et al. Evaluation of gene expression and DNA copy number profiles of adipose tissue-derived stromal cells and consecutive neurosphere-like cells generated from dogs with naturally occurring spinal cord injury. Am J Vet Res. 2017;78:371–380.
175.
LiuRMengXYuX, et al. From 2D to 3D co-culture systems: a review of co-culture models to study the neural cells interaction. Int J Mol Sci. 2022;23:13116.
176.
LossiLAlasiaSSalioC, et al. Cell death and proliferation in acute slices and organotypic cultures of mammalian CNS. Prog Neurobiol. 2009;88:221–245.
177.
LovettMCCoatesJRShuY, et al. Quantitative assessment of hsp70, IL-1β and TNF-α in the spinal cord of dogs with E40K SOD1-associated degenerative myelopathy. Vet J. 2014;200:312–317.
178.
LoweADaltonMSidhuK, et al. Neurogenesis and precursor cell differences in the dorsal and ventral adult canine hippocampus. Neurosci Lett. 2015;593:107–113.
179.
LuoJSuhrSTChangEA, et al. Generation of leukemia inhibitory factor and basic fibroblast growth factor-dependent induced pluripotent stem cells from canine adult somatic cells. Stem Cells Dev. 2011;20:1669–1678.
180.
LuttyGAMathewsMKMergesC, et al. Adenosine stimulates canine retinal microvascular endothelial cell migration and tube formation. Curr Eye Res. 1998;17:594–607.
181.
LuttyGAMergesCGrebeR, et al. Canine retinal angioblasts are multipotent. Exp Eye Res. 2006;83:183–193.
182.
LvWMZhaoYYangG, et al. Role of Ras, ERK, and Akt in glucocorticoid-induced differentiation of embryonic rat somatotropes in vitro. Mol Cell Biochem. 2014;391:67–75.
183.
MadeaB.Importance of supravitality in forensic medicine. Forensic Sci Int. 1994;69:221–241.
184.
MaqsoodMIMatinMMBahramiAR, et al. Immortality of cell lines: challenges and advantages of establishment. Cell Biol Int. 2013;37:1038–1045.
185.
MarksteinerJHumpelC.Beta-amyloid expression, release and extracellular deposition in aged rat brain slices. Mol Psychiatry. 2008;13:939–952.
186.
MatternKMBlancas-VelázquezASNgoMT, et al. The ISL LIM-homeobox 2 transcription factor is negatively regulated by circadian adrenergic signaling to repress the expression of Aanat in pinealocytes of the rat pineal gland. J Pineal Res. 2023;75:e12905.
187.
MattottiMAlvarezZOrtegaJA, et al. Inducing functional radial glia-like progenitors from cortical astrocyte cultures using micropatterned PMMA. Biomaterials. 2012;33:1759–1770.
188.
Medina-RodríguezEMArenzanaFJBribiánA, et al. Protocol to isolate a large amount of functional oligodendrocyte precursor cells from the cerebral cortex of adult mice and humans. PLoS ONE. 2013;8:e81620.
189.
MeletisKBarnabé-HeiderFCarlénM, et al. Spinal cord injury reveals multilineage differentiation of ependymal cells. PLoS Biol. 2008;6:e182.
190.
MenonDVBhaskarSSheshadriP, et al. Positioning canine induced pluripotent stem cells (iPSCs) in the reprogramming landscape of naïve or primed state in comparison to mouse and human iPSCs. Life Sci. 2021;264:118701.
191.
MenonDVPatelDJoshiCG, et al. The road less travelled: the efficacy of canine pluripotent stem cells. Exp Cell Res. 2019;377:94–102.
192.
MewesAFrankeHSingerD.Organotypic brain slice cultures of adult transgenic P301S mice—a model for tauopathy studies. PLoS ONE. 2012;7:e45017.
193.
MilwardEALundbergCGGeB, et al. Isolation and transplantation of multipotential populations of epidermal growth factor-responsive, neural progenitor cells from the canine brain. J Neurosci Res. 1997;50:862–871.
194.
MondalTDasKSinghP, et al. Thin films of functionalized carbon nanotubes support long-term maintenance and cardio-neuronal differentiation of canine induced pluripotent stem cells. Nanomedicine. 2022;40:102487.
195.
MooreSA.The spinal ependymal layer in health and disease. Vet Pathol. 2016;53:746–753.
196.
MooreSAOglesbeeMJ.Spinal cord ependymal responses to naturally occurring traumatic spinal cord injury in dogs. Vet Pathol. 2015;52:1108–1117.
NakanoREdamuraKNakayamaT, et al. Differentiation of canine bone marrow stromal cells into voltage- and glutamate-responsive neuron-like cells by basic fibroblast growth factor. J Vet Med Sci. 2015;77:27–35.
199.
NardoneRHöllerYTaylorAC, et al. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis. Zoology (Jena). 2016;119:64–73.
200.
NascimentoJMGouvêa-JunqueiraDZuccoliGS, et al. Zika virus strains and dengue virus induce distinct proteomic changes in neural stem cells and neurospheres. Mol Neurobiol. 2022;59:5549–5563.
Nieto-SampedroM.Central nervous system lesions that can and those that cannot be repaired with the help of olfactory bulb ensheathing cell transplants. Neurochem Res. 2003;28:1659–1676.
203.
NikolakopoulouPRautiRVoulgarisD, et al. Recent progress in translational engineered in vitro models of the central nervous system. Brain. 2020;143:3181–3213.
204.
NikonovSDolgovaNSudharsanR, et al. Photochemical restoration of light sensitivity in the degenerated canine retina. Pharmaceutics. 2022;14:2711.
205.
NishimuraTHatoyaSKanegiR, et al. Generation of functional platelets from canine induced pluripotent stem cells. Stem Cells Dev. 2013;22:2026–2035.
206.
NoguchiSInoueMIchikawaT, et al. The NRG3/ERBB4 signaling cascade as a novel therapeutic target for canine glioma. Exp Cell Res. 2021;400:112504.
207.
OhnishiTMatsumuraHIzumotoS, et al. A novel model of glioma cell invasion using organotypic brain slice culture. Cancer Res. 1998;58:2935–2940.
208.
OlbyNJda CostaRCLevineJM, et al. Prognostic factors in canine acute intervertebral disc disease. Front Vet Sci. 2020;7:596059.
209.
OmarMBockPKreutzerR, et al. Defining the morphological phenotype: 2’,3’-cyclic nucleotide 3’-phosphodiesterase (CNPase) is a novel marker for in situ detection of canine but not rat olfactory ensheathing cells. Cell Tissue Res. 2011;344:391–405.
210.
OmarMHansmannFKreutzerR, et al. Cell type- and isotype-specific expression and regulation of β-tubulins in primary olfactory ensheathing cells and Schwann cells in vitro. Neurochem Res. 2013;38:981–988.
211.
Orlando D’cundiEA. In Vitro Susceptibility Of Glial Cells Obtained From The Adult Canine Brain For Different Strains Of Canine Distemper Virus. Hannover: Tierärztliche Hochschule; 2009.
212.
OrlandoEAImbschweilerIGerhauserI, et al. In vitro characterization and preferential infection by canine distemper virus of glial precursors with Schwann cell characteristics from adult canine brain. Neuropathol Appl Neurobiol. 2008;34:621–637.
213.
PaganiIOttoboniLPodiniP, et al. Heparin protects human neural progenitor cells from zika virus-induced cell death while preserving their differentiation into mature neuroglial cells. J Virol. 2022;96:e0112222.
214.
ParatiEABezAPontiD, et al. Neural stem cells. Biological Features and Therapeutic Potential in Parkinson’s Disease. J Neurosurg Sci. 2003;47:8–17.
215.
PartridgeBRossmeislJH.Companion animal models of neurological disease. J Neurosci Methods. 2020;331:108484.
216.
Pearce-KellingSMitchellWJSummersBA, et al. Growth of canine distemper virus in cultured astrocytes: relationship to in vivo persistence and disease. Microb Pathog. 1990;8:71–82.
217.
Pearce-KellingSMitchellWJSummersBA, et al. Virulent and attenuated canine distemper virus infects multiple dog brain cell types in vitro. Glia. 1991;4:408–416.
218.
PennesiMENeuringerMCourtneyRJ.Animal models of age related macular degeneration. Mol Aspects Med. 2012;33:487–509.
219.
PenningLCvan den BoomR.Companion animal organoid technology to advance veterinary regenerative medicine. Front Vet Sci. 2023;10:1032835.
220.
Petersen-JonesSM. Animal models of human retinal dystrophies. Eye (Lond). 1998;12(pt 3b):566–570.
PfenningerCVSteinhoffCHertwigF, et al. Prospectively isolated CD133/CD24-positive ependymal cells from the adult spinal cord and lateral ventricle wall differ in their long-term in vitro self-renewal and in vivo gene expression. Glia. 2011;59:68–81.
223.
PluchinoSZanottiLDeleidiM, et al. Neural stem cells and their use as therapeutic tool in neurological disorders. Brain Res Brain Res Rev. 2005;48:211–219.
224.
PreatoAPinheiroERosenstockT, et al. The relevance of astrocytic cell culture models for neuroinflammation in neurodegeneration research. Neuroglia. 2024;5:27–49.
225.
PrinzMErnyDHagemeyerN.Ontogeny and homeostasis of CNS myeloid cells. Nat Immunol. 2017;18:385–392.
226.
PriyathilakaTTLaakerCJHerbathM, et al. Modeling infectious diseases of the central nervous system with human brain organoids. Transl Res. 2022;250:18–35.
227.
Prpar MihevcSKokondoska GrgichVKopitarAN, et al. Neural differentiation of canine mesenchymal stem cells/multipotent mesenchymal stromal cells. BMC Vet Res. 2020;16:282.
228.
Prpar MihevcSMajdičG. Canine cognitive dysfunction and Alzheimer’s disease—two facets of the same disease?Front Neurosci. 2019;13:604.
229.
PuglieseMGangitanoCCeccarigliaS, et al. Canine cognitive dysfunction and the cerebellum: acetylcholinesterase reduction, neuronal and glial changes. Brain Res. 2007;1139:85–94.
230.
QiGTangHHuJ, et al. Potential role of tanycyte-derived neurogenesis in Alzheimer’s disease. Neural Regen Res. 2024;20:1599–1612.
231.
QianXJacobFSongMM, et al. Generation of human brain region–specific organoids using a miniaturized spinning bioreactor. Nature Protocols. 2018;13:565–580.
232.
QianXNguyen HaNSong MingxiM, et al. Brain-region-specific organoids using mini-bioreactors for modeling ZIKV exposure. Cell. 2016;165:1238–1254.
233.
QuadrosAPatelNCrescentiniR, et al. Increased TNFα production and Cox-2 activity in organotypic brain slice cultures from APPsw transgenic mice. Neurosci Lett. 2003;353:66–68.
234.
RainovNGKochSSena-EstevesM, et al. Characterization of a canine glioma cell line as related to established experimental brain tumor models. J Neuropathol Exp Neurol. 2000;59:607–613.
235.
RajaWKNevesEBurkeC, et al. Patient-derived three-dimensional cortical neurospheres to model Parkinson’s disease. PLoS ONE. 2022;17:e0277532.
236.
RaviVMJosephKWurmJ, et al. Human organotypic brain slice culture: a novel framework for environmental research in neuro-oncology. Life Sci Alliance. 2019;2:e201900305.
237.
ReichenbachABringmannA.New functions of Müller cells. Glia. 2013;61:651–678.
238.
RichterMPiwockaOMusielakM, et al. From donor to the lab: a fascinating journey of primary cell lines. Front Cell Dev Biol. 2021;9:711381.
239.
RobertsTMcGreevyPValenzuelaM.Human induced rotation and reorganization of the brain of domestic dogs. PLoS ONE. 2010;5:e11946.
RoloffFZiegeSBaumgärtnerW, et al. Schwann cell-free adult canine olfactory ensheathing cell preparations from olfactory bulb and mucosa display differential migratory and neurite growth-promoting properties in vitro. BMC Neurosci. 2013;14:141.
242.
RoszekKMakowskaNCzarneckaJ, et al. Canine adipose-derived stem cells: purinergic characterization and neurogenic potential for therapeutic applications. J Cell Biochem. 2017;118:58–65.
243.
RouleauNMuruganNJKaplanDL.Functional bioengineered models of the central nervous system. Nat Rev Bioeng. 2023;1:252–270.
244.
RupleAMacLeanESnyder-MacklerN, et al. Dog models of aging. Annu Rev Anim Biosci. 2022;10:419–439.
245.
RyuHHLimJHByeonYE, et al. Functional recovery and neural differentiation after transplantation of allogenic adipose-derived stem cells in a canine model of acute spinal cord injury. J Vet Sci. 2009;10:273–284.
246.
SagoKTamaharaSTomihariM, et al. In vitro differentiation of canine celiac adipose tissue-derived stromal cells into neuronal cells. J Vet Med Sci. 2008;70:353–357.
247.
SalihSNizamudeenZADe MeloN, et al. Sox-positive cell population in the adult cerebellum increases upon tissue degeneration. Exp Neurol. 2022;348:113950.
248.
Salinas TejedorLBernerGJacobsenK, et al. Mesenchymal stem cells do not exert direct beneficial effects on CNS remyelination in the absence of the peripheral immune system. Brain Behav Immun. 2015;50:155–165.
249.
SalminVVKomlevaYKKuvachevaNV, et al. Differential roles of environmental enrichment in Alzheimer’s type of neurodegeneration and physiological aging. Front Aging Neurosci. 2017;9:245.
250.
SantosSIPde OliveiraVCPieriNCG, et al. Isolation and characterization of neural stem cells from fetal canine spinal cord. Neurosci Lett. 2021;765:136293.
251.
SchneiderMRAdlerHBraunJ, et al. Canine embryo-derived stem cells–toward clinically relevant animal models for evaluating efficacy and safety of cell therapies. Stem Cells. 2007;25:1850–1851.
252.
SchneiderMRWolfEBraunJ, et al. Canine embryo-derived stem cells and models for human diseases. Hum Mol Genet. 2008;17:R42–R47.
253.
SchneiderMRWolfEBraunJ, et al. Canine embryonic stem cells: state of the art. Theriogenology. 2010;74:492–497.
254.
SchnichelsSKieblerTHurstJ, et al. Retinal organ cultures as alternative research models. Altern Lab Anim. 2019;47:19–29.
255.
SchobesbergerMZurbriggenASummerfieldA, et al. Oligodendroglial degeneration in distemper: apoptosis or necrosis?Acta Neuropathol. 1999;97:279–287.
256.
SchommerJSchragMNackenoffA, et al. Method for organotypic tissue culture in the aged animal. Methodsx. 2017;4:166–171.
257.
SchrockMSZalenskiAATallmanMM, et al. Establishment and characterization of two novel patient-derived lines from canine high-grade glioma. Vet Comp Oncol. 2023;21:492–502.
258.
SeehusenFBaumgärtnerW.Axonal pathology and loss precede demyelination and accompany chronic lesions in a spontaneously occurring animal model of multiple sclerosis. Brain Pathol. 2010;20:551–559.
259.
SeehusenFOrlandoEAWewetzerK, et al. Vimentin-positive astrocytes in canine distemper: a target for canine distemper virus especially in chronic demyelinating lesions?Acta Neuropathol. 2007;114:597–608.
260.
SeryoginaESKamyninaAVKoroevDO, et al. RAGE induces physiological activation of NADPH oxidase in neurons and astrocytes and neuroprotection. FEBS J. 2024;291:1944–1957.
261.
SgubinDWakimotoHKanaiR, et al. Oncolytic herpes simplex virus counteracts the hypoxia-induced modulation of glioblastoma stem-like cells. Stem Cells Transl Med. 2012;1:322–332.
262.
ShaLMillerSMSzurszewskiJH.Morphology and electrophysiology of neurons in dog paraventricular nucleus: in vitro study. Brain Res. 2004;1010:95–107.
263.
ShimadaHNakadaAHashimotoY, et al. Generation of canine-induced pluripotent stem cells by retroviral transduction and chemical inhibitors. Mol Reprod Dev. 2009;77:2.
264.
Silva-PedrosaRSalgadoAJFerreiraPE.Revolutionizing disease modeling: the emergence of organoids in cellular systems. Cells. 2023;12:930.
265.
SingethanKHiltenspergerGKendlS, et al. N-(3-Cyanophenyl)-2-phenylacetamide, an effective inhibitor of morbillivirus-induced membrane fusion with low cytotoxicity. J Gen Virol. 2010;91:2762–2772.
266.
SiracusaRFuscoRCuzzocreaS.Astrocytes: role and functions in brain pathologies. Front Pharmacol. 2019;10:1114.
267.
SmirnovaLHartungT.The promise and potential of brain organoids. Adv Healthc Mater. 2024;21:e2302745.
268.
SmithPMLakatosABarnettSC, et al. Cryopreserved cells isolated from the adult canine olfactory bulb are capable of extensive remyelination following transplantation into the adult rat CNS. Exp Neurol. 2002;176:402–406.
269.
SneddonLUHalseyLGBuryNR.Considering aspects of the 3Rs principles within experimental animal biology. J Exp Biol. 2017;220:3007–3016.
SoniNTripathiAMukherjeeS, et al. Bone marrow-derived extracellular vesicles modulate the abundance of infiltrating immune cells in the brain and exert an antiviral effect against the Japanese encephalitis virus. FASEB Bioadv. 2022;4:798–815.
272.
SottileVLiMScottingPJ.Stem cell marker expression in the Bergmann glia population of the adult mouse brain. Brain Res. 2006;1099:8–17.
273.
SpitzbarthIBockPHaistV, et al. Prominent microglial activation in the early proinflammatory immune response in naturally occurring canine spinal cord injury. J Neuropathol Exp Neurol. 2011;70:703–714.
274.
SpitzbarthILemppCKeglerK, et al. Immunohistochemical and transcriptome analyses indicate complex breakdown of axonal transport mechanisms in canine distemper leukoencephalitis. Brain Behav. 2016;6:e00472.
275.
SpitzbarthIMooreSASteinVM, et al. Current insights into the pathology of canine intervertebral disc extrusion-induced spinal cord injury. Front Vet Sci. 2020;7:595796.
276.
StarkeyMPScaseTJMellershCS, et al. Dogs really are man’s best friend–canine genomics has applications in veterinary and human medicine! Brief Funct Genomic Proteomic. 2005;4:112–128.
277.
StavridisSIDehghaniFKorfHW, et al. Characterisation of transverse slice culture preparations of postnatal rat spinal cord: preservation of defined neuronal populations. Histochem Cell Biol. 2005;123:377–392.
278.
SteinVMCzubMHansenR, et al. Characterization of canine microglial cells isolated ex vivo. Vet Immunol Immunopathol. 2004;99:73–85.
279.
SteinVMCzubMSchreinerN, et al. Microglial cell activation in demyelinating canine distemper lesions. J Neuroimmunol. 2004;153:122–131.
280.
StoicaGLunguGMartini-StoicaH, et al. Identification of cancer stem cells in dog glioblastoma. Vet Pathol. 2009;46:391–406.
281.
StoppiniLBuchsPAMullerD.A simple method for organotypic cultures of nervous tissue. J Neurosci Methods. 1991;37:173–182.
282.
StoryBDMillerMEBradburyAM, et al. Canine models of inherited musculoskeletal and neurodegenerative diseases. Front Vet Sci. 2020;7:80.
283.
SummersBAAppelMJ.Aspects of canine distemper virus and measles virus encephalomyelitis. Neuropathol Appl Neurobiol. 1994;20:525–534.
284.
SunXYJuXCLiY, et al. Generation of vascularized brain organoids to study neurovascular interactions. eLife. 2022;11:e76707.
285.
SwinglerMDonadoniMBellizziA, et al. IPSC-derived three-dimensional brain organoid models and neurotropic viral infections. J Neurovirol. 2023;29:121–134.
286.
TakahashiKYamanakaS.Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006;126:663–676.
287.
TamakiSJJacobsYDohseM, et al. Neuroprotection of host cells by human central nervous system stem cells in a mouse model of infantile neuronal ceroid lipofuscinosis. Cell Stem Cell. 2009;5:310–319.
288.
TechangamsuwanSHaasLRohnK, et al. Distinct cell tropism of canine distemper virus strains to adult olfactory ensheathing cells and Schwann cells in vitro. Virus Res. 2009;144:195–201.
289.
TechangamsuwanSImbschweilerIKreutzerR, et al. Similar behaviour and primate-like properties of adult canine Schwann cells and olfactory ensheathing cells in long-term culture. Brain Res. 2008;1240:31–38.
290.
TechangamsuwanSKreutzerRKreutzerM, et al. Transfection of adult canine Schwann cells and olfactory ensheathing cells at early and late passage with human TERT differentially affects growth factor responsiveness and in vitro growth. J Neurosci Methods. 2009;176:112–120.
291.
TsukamotoMNishimuraTYodoeK, et al. Generation of footprint-free canine induced pluripotent stem cells using auto-erasable sendai virus vector. Stem Cells Dev. 2018;27:1577–1586.
292.
UrsavasSDariciHKaraozE.Olfactory ensheathing cells: unique glial cells promising for treatments of spinal cord injury. J Neurosci Res. 2021;99:1579–1597.
293.
VaagsAKRosic-KablarSGartleyCJ, et al. Derivation and characterization of canine embryonic stem cell lines with in vitro and in vivo differentiation potential. Stem Cells. 2009;27:329–340.
294.
ValenzuelaMJDeanSKSachdevP, et al. Neural precursors from canine skin: a new direction for testing autologous cell replacement in the brain. Stem Cells Dev. 2008;17:1087–1094.
295.
VandeveldeMZurbriggenA.Demyelination in canine distemper virus infection: a review. Acta Neuropathol. 2005;109:56–68.
296.
VandeveldeMZurbriggenADumasM, et al. Canine distemper virus does not infect oligodendrocytes in vitro. J Neurol Sci. 1985;69:133–137.
297.
VandeveldeMZurbriggenAHigginsRJ, et al. Spread and distribution of viral antigen in nervous canine distemper. Acta Neuropathol. 1985;67:211–218.
298.
van NiekerkEAKawaguchiRMarquesdeFreriaC, et al. Methods for culturing adult CNS neurons reveal a CNS conditioning effect. Cell Rep Methods. 2022;2:100255.
299.
VerwerRWBakerREBoitenEF, et al. Post-mortem brain tissue cultures from elderly control subjects and patients with a neurodegenerative disease. Exp Gerontol. 2003;38:167–172.
300.
VinokurovAYDreminVVPiavchenkoGA, et al. Assessment of mitochondrial membrane potential and NADH redox state in acute brain slices. Methods Mol Biol. 2021;2276:193–202.
301.
WalczakPAPerez-EstebanPBassettDC, et al. Modelling the central nervous system: tissue engineering of the cellular microenvironment. Emerg Top Life Sci. 2021;5:507–517.
302.
WaltonRMParmentierTWolfeJH.Postnatal neural precursor cell regions in the rostral subventricular zone, hippocampal subgranular zone and cerebellum of the dog (Canis lupus familiaris). Histochem Cell Biol. 2013;139:415–429.
303.
WaltonRMWolfeJH.Abnormalities in neural progenitor cells in a dog model of lysosomal storage disease. J Neuropathol Exp Neurol. 2007;66:760–769.
304.
WangDYanBRajapakshaWR, et al. The expression of voltage-gated ca2+ channels in pituicytes and the up-regulation of L-type ca2+ channels during water deprivation. J Neuroendocrinol. 2009;21:858–866.
305.
WangLLZhangCL.In vivo glia-to-neuron conversion: pitfalls and solutions. Dev Neurobiol. 2022;82:367–374.
306.
WatanabeFSchoefflerAFairSR, et al. Generation of neurosphere-derived organoid-like-aggregates (NEDAS) from neural stem cells. Curr Protoc. 2021;1:e15.
307.
WeilM-TSchulz-ËberlinGMukherjeeC, et al. Isolation and culture of oligodendrocytes. In: LyonsDAKegelL, eds. Oligodendrocytes: Methods and Protocols. New York: Springer; 2019:79–95.
308.
WelschJCLionnetCTerzianC, et al. Organotypic brain cultures: a framework for studying CNS infection by neurotropic viruses and screening antiviral drugs. Bio Protoc. 2017;7:e2605.
309.
WerlingLLJacocksHM3rdRosenthalRE, et al. Dopamine release from canine striatum following global cerebral ischemia/reperfusion. Brain Res. 1993;606:99–105.
310.
WewetzerKGrotheCClausP.In vitro expression and regulation of ciliary neurotrophic factor and its alpha receptor subunit in neonatal rat olfactory ensheathing cells. Neurosci Lett. 2001;306:165–168.
311.
WewetzerKRadtkeCKocsisJ, et al. Species-specific control of cellular proliferation and the impact of large animal models for the use of olfactory ensheathing cells and Schwann cells in spinal cord repair. Exp Neurol. 2011;229:80–87.
312.
WewetzerKVerdúEAngelovDN, et al. Olfactory ensheathing glia and Schwann cells: two of a kind?Cell Tissue Res. 2002;309:337–345.
313.
WhitworthDJOvchinnikovDAWolvetangEJ.Generation and characterization of LIF-dependent canine induced pluripotent stem cells from adult dermal fibroblasts. Stem Cells Dev. 2012;21:2288–2297.
314.
WiikACRopstadEOEkestenB, et al. Progressive retinal atrophy in Shetland sheepdog is associated with a mutation in the CNGA1 gene. Anim Genet. 2015;46:515–521.
315.
WilcoxJTLaiJKSempleE, et al. Synaptically-competent neurons derived from canine embryonic stem cells by lineage selection with EGF and Noggin. Plos One. 2011;6:e19768.
316.
WilhelmiESchöderUHBenabdallahA, et al. Organotypic brain-slice cultures from adult rats: approaches for a prolonged culture time. Altern Lab Anim. 2002;30:275–283.
317.
WinklerPAOccelliLMPetersen-JonesSM.Large animal models of inherited retinal degenerations: a review. Cells. 2020;9:882.
318.
Wyss-FluehmannGZurbriggenAVandeveldeM, et al. Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein. Acta Neuropathol. 2010;119:617–630.
319.
XiangZHrabetovaSMoskowitzSI, et al. Long-term maintenance of mature hippocampal slices in vitro. J Neurosci Methods. 2000;98:145–154.
320.
XueYJCuiSSGuoDC, et al. Development of a method for the isolation and culture of astrocytes from the canine cerebral cortex. J Neurosci Methods. 2022;370:109476.
321.
YamadaKWatanabeM.Cytodifferentiation of Bergmann glia and its relationship with Purkinje cells. Anat Sci Int. 2002;77:94–108.
322.
YasumuraYTeshimaTNagashimaT, et al. Immortalized canine adipose-derived mesenchymal stem cells as a novel candidate cell source for mesenchymal stem cell therapy. Int J Mol Sci. 2023;24:2250.
323.
YorkDHigginsRJLeCouteurRA, et al. TP53 mutations in canine brain tumors. Vet Pathol. 2012;49:796–801.
324.
YoshiiK.Epidemiology and pathological mechanisms of tick-borne encephalitis. J Vet Med Sci. 2019;81:343–347.
325.
YoshimatsuSEdamuraKYoshiiY, et al. Non-viral derivation of a transgene-free induced pluripotent stem cell line from a male beagle dog. Stem Cell Res. 2021;53:102375.
326.
YuJMBunnellBAKangS-K.Neural differentiation of human adipose tissue-derived stem cells. In: GimbleJMBunnellBA, eds. Adipose-derived Stem Cells: Methods and Protocols. Totowa, NJ: Humana Press; 2011:219–231.
327.
ZhangHDuYQiL, et al. Targeting GBM with an oncolytic picornavirus SVV-001 alone and in combination with fractionated radiation in a novel panel of orthotopic PDX models. J Transl Med. 2023;21:444.
328.
ZhangWJiangJXuZ, et al. Microglia-containing human brain organoids for the study of brain development and pathology. Mol Psychiatry. 2023;28:96–107.
329.
ZhangXWangWJinZB.Retinal organoids as models for development and diseases. Cell Regen. 2021;10:33.
330.
ZhaoJRenY.Multiple receptors involved in invasion and neuropathogenicity of canine distemper virus: a review. Viruses. 2022;14:1520.
331.
ZhengHHFuPFChenHY, et al. Pseudorabies virus: from pathogenesis to prevention strategies. Viruses. 2022;14:1638.
332.
ZhengWKlammerAMNaciriJN, et al. Patterns of herpes simplex virus 1 infection in neural progenitor cells. J Virol. 2020;94:e00994.
333.
ZhongHYuHSunJ, et al. Isolation of microglia from retinas of chronic ocular hypertensive rats. Open Life Sci. 2021;16:992–1001.
334.
ZhuFShiQJiangYH, et al. Impaired synaptic function and hyperexcitability of the pyramidal neurons in the prefrontal cortex of autism-associated Shank3 mutant dogs. Mol Autism. 2024;15:9.
335.
ZhuLMiarkaLBaenaP, et al. Protocol to generate murine organotypic brain cultures for drug screening and evaluation of anti-metastatic efficacy. STAR Protoc. 2023;4:102194.
336.
ZiegeSBaumgartnerWWewetzerK.Toward defining the regenerative potential of olfactory mucosa: establishment of Schwann cell-free adult canine olfactory ensheathing cell preparations suitable for transplantation. Cell Transplant. 2013;22:355–367.
337.
ZurbriggenADumasMVandeveldeM.Neurons in dissociated canine brain cell cultures. Zentralbl Veterinarmed A. 1987;34:673–678.
338.
ZurbriggenAGraberHUWagnerA, et al. Canine distemper virus persistence in the nervous system is associated with noncytolytic selective virus spread. J Virol. 1995;69:1678–1686.
ZurbriggenAVandeveldeMBeranekCF, et al. Morphological and immunocytochemical characterisation of mixed glial cell cultures derived from neonatal canine brain. Res Vet Sci. 1984;36:270–275.
341.
ZurbriggenAVandeveldeMBolloE.Demyelinating, non-demyelinating and attenuated canine distemper virus strains induce oligodendroglial cytolysis in vitro. J Neurol Sci. 1987;79:33–41.
342.
ZurbriggenAVandeveldeMDumasM, et al. Oligodendroglial pathology in canine distemper virus infection in vitro. Acta Neuropathol. 1987;74:366–373.
343.
ZurbriggenAVandeveldeMSteckA, et al. Myelin-associated glycoprotein is produced before myelin basic protein in cultured oligodendrocytes. J Neuroimmunol. 1984;6:41–49.
344.
ZurbriggenAYamawakiMVandeveldeM.Restricted canine distemper virus infection of oligodendrocytes. Lab Invest. 1993;68:277–284.
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