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  1. Article ; Online: In Vitro Effects of Methylprednisolone over Oligodendroglial Cells: Foresight to Future Cell Therapies.

    Gómez-Pinedo, Ulises / Matías-Guiu, Jordi A / Ojeda-Hernandez, Denise / de la Fuente-Martin, Sarah / Kamal, Ola Mohamed-Fathy / Benito-Martin, Maria Soledad / Selma-Calvo, Belen / Montero-Escribano, Paloma / Matías-Guiu, Jorge

    Cells

    2023  Volume 12, Issue 11

    Abstract: The implantation of oligodendrocyte precursor cells may be a useful therapeutic strategy for targeting remyelination. However, it is yet to be established how these cells behave after implantation and whether they retain the capacity to proliferate or ... ...

    Abstract The implantation of oligodendrocyte precursor cells may be a useful therapeutic strategy for targeting remyelination. However, it is yet to be established how these cells behave after implantation and whether they retain the capacity to proliferate or differentiate into myelin-forming oligodendrocytes. One essential issue is the creation of administration protocols and determining which factors need to be well established. There is controversy around whether these cells may be implanted simultaneously with corticosteroid treatment, which is widely used in many clinical situations. This study assesses the influence of corticosteroids on the capacity for proliferation and differentiation and the survival of human oligodendroglioma cells. Our findings show that corticosteroids reduce the capacity of these cells to proliferate and to differentiate into oligodendrocytes and decrease cell survival. Thus, their effect does not favour remyelination; this is consistent with the results of studies with rodent cells. In conclusion, protocols for the administration of oligodendrocyte lineage cells with the aim of repopulating oligodendroglial niches or repairing demyelinated axons should not include corticosteroids, given the evidence that the effects of these drugs may undermine the objectives of cell transplantation.
    MeSH term(s) Humans ; Methylprednisolone/pharmacology ; Oligodendroglia ; Myelin Sheath ; Axons ; Cell Differentiation
    Chemical Substances Methylprednisolone (X4W7ZR7023)
    Language English
    Publishing date 2023-05-30
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells12111515
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Nose-to-Brain: The Next Step for Stem Cell and Biomaterial Therapy in Neurological Disorders.

    Villar-Gómez, Natalia / Ojeda-Hernandez, Doddy Denise / López-Muguruza, Eneritz / García-Flores, Silvia / Bonel-García, Natalia / Benito-Martín, María Soledad / Selma-Calvo, Belen / Canales-Aguirre, Alejandro Arturo / Mateos-Díaz, Juan Carlos / Montero-Escribano, Paloma / Matias-Guiu, Jordi A / Matías-Guiu, Jorge / Gómez-Pinedo, Ulises

    Cells

    2022  Volume 11, Issue 19

    Abstract: Neurological disorders are a leading cause of morbidity worldwide, giving rise to a growing need to develop treatments to revert their symptoms. This review highlights the great potential of recent advances in cell therapy for the treatment of ... ...

    Abstract Neurological disorders are a leading cause of morbidity worldwide, giving rise to a growing need to develop treatments to revert their symptoms. This review highlights the great potential of recent advances in cell therapy for the treatment of neurological disorders. Through the administration of pluripotent or stem cells, this novel therapy may promote neuroprotection, neuroplasticity, and neuroregeneration in lesion areas. The review also addresses the administration of these therapeutic molecules by the intranasal route, a promising, non-conventional route that allows for direct access to the central nervous system without crossing the blood-brain barrier, avoiding potential adverse reactions and enabling the administration of large quantities of therapeutic molecules to the brain. Finally, we focus on the need to use biomaterials, which play an important role as nutrient carriers, scaffolds, and immune modulators in the administration of non-autologous cells. Little research has been conducted into the integration of biomaterials alongside intranasally administered cell therapy, a highly promising approach for the treatment of neurological disorders.
    MeSH term(s) Administration, Intranasal ; Biocompatible Materials/therapeutic use ; Brain ; Humans ; Nervous System Diseases/therapy ; Stem Cells
    Chemical Substances Biocompatible Materials
    Language English
    Publishing date 2022-10-01
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2661518-6
    ISSN 2073-4409 ; 2073-4409
    ISSN (online) 2073-4409
    ISSN 2073-4409
    DOI 10.3390/cells11193095
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2.

    Sanclemente-Alaman, Inmaculada / Moreno-Jiménez, Lidia / Benito-Martín, María Soledad / Canales-Aguirre, Alejandro / Matías-Guiu, Jordi A / Matías-Guiu, Jorge / Gómez-Pinedo, Ulises

    Frontiers in immunology

    2020  Volume 11, Page(s) 2163

    Abstract: Introduction: The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic ... ...

    Abstract Introduction: The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions.
    Development: We reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus' action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids.
    Conclusion: Given the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.
    MeSH term(s) Animals ; Betacoronavirus ; COVID-19 ; Cell Line, Tumor ; Central Nervous System Infections/complications ; Central Nervous System Infections/immunology ; Central Nervous System Infections/virology ; Coronavirus Infections/complications ; Coronavirus Infections/immunology ; Coronavirus Infections/virology ; Cricetinae ; Disease Models, Animal ; HEK293 Cells ; Humans ; Mice ; Organoids ; Pandemics ; Pneumonia, Viral/complications ; Pneumonia, Viral/immunology ; Pneumonia, Viral/virology ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-08-28
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.02163
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Sera from Patients with NMOSD Reduce the Differentiation Capacity of Precursor Cells in the Central Nervous System.

    Gómez-Pinedo, Ulises / García-Ávila, Yolanda / Gallego-Villarejo, Lucía / Matías-Guiu, Jordi A / Benito-Martín, María Soledad / Esteban-García, Noelia / Sanclemente-Alamán, Inmaculada / Pytel, Vanesa / Moreno-Jiménez, Lidia / Sancho-Bielsa, Francisco / Vidorreta-Ballesteros, Lucía / Montero-Escribano, Paloma / Matías-Guiu, Jorge

    International journal of molecular sciences

    2021  Volume 22, Issue 10

    Abstract: Introduction: AQP4 (aquaporin-4)-immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination ...

    Abstract Introduction: AQP4 (aquaporin-4)-immunoglobulin G (IgG)-mediated neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease that affects the central nervous system, particularly the spinal cord and optic nerve; remyelination capacity in neuromyelitis optica is yet to be determined, as is the role of AQP4-IgG in cell differentiation.
    Material and methods: We included three groups-a group of patients with AQP4-IgG-positive neuromyelitis optica, a healthy group, and a sham group. We analyzed differentiation capacity in cultures of neurospheres from the subventricular zone of mice by adding serum at two different times: early and advanced stages of differentiation. We also analyzed differentiation into different cell lines.
    Results and conclusions: The effect of sera from patients with NMOSD on precursor cells differs according to the degree of differentiation, and probably affects oligodendrocyte progenitor cells from NG2 cells to a lesser extent than cells from the subventricular zone; however, the resulting oligodendrocytes may be compromised in terms of maturation and possibly limited in their ability to generate myelin. Furthermore, these cells decrease in number with age. It is very unlikely that the use of drugs favoring the migration and differentiation of oligodendrocyte progenitor cells in multiple sclerosis would be effective in the context of neuromyelitis optica, but cell therapy with oligodendrocyte progenitor cells seems to be a potential alternative.
    MeSH term(s) Animals ; Aquaporin 4/immunology ; Autoantibodies/blood ; Autoantibodies/immunology ; Case-Control Studies ; Cell Differentiation ; Central Nervous System/immunology ; Central Nervous System/pathology ; Cerebellum/immunology ; Cerebellum/pathology ; Female ; Humans ; Immunoglobulin G/immunology ; Male ; Mice, Inbred BALB C ; Middle Aged ; Neuromyelitis Optica/blood ; Neuromyelitis Optica/immunology ; Neuromyelitis Optica/pathology ; Oligodendrocyte Precursor Cells/immunology ; Oligodendrocyte Precursor Cells/pathology ; Mice
    Chemical Substances AQP4 protein, human ; Aquaporin 4 ; Autoantibodies ; Immunoglobulin G
    Language English
    Publishing date 2021-05-14
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22105192
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: The Integration of Cell Therapy and Biomaterials as Treatment Strategies for Remyelination.

    López-Muguruza, Eneritz / Villar-Gómez, Natalia / Matias-Guiu, Jordi A / Selma-Calvo, Belen / Moreno-Jiménez, Lidia / Sancho-Bielsa, Francisco / Lopez-Carbonero, Juan / Benito-Martín, María Soledad / García-Flores, Silvia / Bonel-García, Natalia / Kamal, Ola Mohamed-Fathy / Ojeda-Hernández, Denise / Matías-Guiu, Jorge / Gómez-Pinedo, Ulises

    Life (Basel, Switzerland)

    2022  Volume 12, Issue 4

    Abstract: Multiple sclerosis (MS) is a chronic degenerative autoimmune disease of the central nervous system that causes inflammation, demyelinating lesions, and axonal damage and is associated with a high rate of early-onset disability. Disease-modifying ... ...

    Abstract Multiple sclerosis (MS) is a chronic degenerative autoimmune disease of the central nervous system that causes inflammation, demyelinating lesions, and axonal damage and is associated with a high rate of early-onset disability. Disease-modifying therapies are used to mitigate the inflammatory process in MS but do not promote regeneration or remyelination; cell therapy may play an important role in these processes, modulating inflammation and promoting the repopulation of oligodendrocytes, which are responsible for myelin repair. The development of genetic engineering has led to the emergence of stable, biocompatible biomaterials that may promote a favorable environment for exogenous cells. This review summarizes the available evidence about the effects of transplantation of different types of stem cells reported in studies with several animal models of MS and clinical trials in human patients. We also address the advantages of combining cell therapy with biomaterials.
    Language English
    Publishing date 2022-03-24
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life12040474
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome.

    Díez-Cirarda, Maria / Yus-Fuertes, Miguel / Sanchez-Sanchez, Rafael / Gonzalez-Rosa, Javier J / Gonzalez-Escamilla, Gabriel / Gil-Martínez, Lidia / Delgado-Alonso, Cristina / Gil-Moreno, Maria Jose / Valles-Salgado, Maria / Cano-Cano, Fatima / Ojeda-Hernandez, Denise / Gomez-Ruiz, Natividad / Oliver-Mas, Silvia / Benito-Martín, María Soledad / Jorquera, Manuela / de la Fuente, Sarah / Polidura, Carmen / Selma-Calvo, Belén / Arrazola, Juan /
    Matias-Guiu, Jorge / Gomez-Pinedo, Ulises / Matias-Guiu, Jordi A

    EBioMedicine

    2023  Volume 94, Page(s) 104711

    Abstract: Background: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in ... ...

    Abstract Background: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition.
    Methods: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls.
    Findings: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase.
    Interpretation: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase.
    Funding: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund "A way to make Europe" (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund "A way to make Europe") (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).
    MeSH term(s) Humans ; SARS-CoV-2 ; COVID-19/pathology ; Brain/diagnostic imaging ; Brain/pathology ; Hippocampus/pathology ; Atrophy ; Syndrome ; Biomarkers
    Chemical Substances Biomarkers
    Language English
    Publishing date 2023-07-13
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2851331-9
    ISSN 2352-3964
    ISSN (online) 2352-3964
    DOI 10.1016/j.ebiom.2023.104711
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  7. Article ; Online: Vitamin D increases remyelination by promoting oligodendrocyte lineage differentiation.

    Gomez-Pinedo, Ulises / Cuevas, Jesús Adriel / Benito-Martín, María Soledad / Moreno-Jiménez, Lidia / Esteban-Garcia, Noelia / Torre-Fuentes, Laura / Matías-Guiu, Jordi A / Pytel, Vanesa / Montero, Paloma / Matías-Guiu, Jorge

    Brain and behavior

    2019  Volume 10, Issue 1, Page(s) e01498

    Abstract: Introduction: Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in ... ...

    Abstract Introduction: Several experimental studies have suggested the potential remyelinating effects of vitamin D (VitD) supplements regardless of the presence of VitD deficiency. This study aims to analyze neurogenesis in a model of toxic demyelination in order to evaluate the effects of VitD on demyelination and remyelination.
    Material and methods: We used 24 male Wistar rats that had received surgical lesions to the corpus callosum and were injected with lysolecithin. Rats were divided into three groups: Group 1 included eight rats with lesions to the corpus callosum but not lysolecithin injections (sham group), group 2 included eight rats with lesions to the corpus callosum that were injected with lysolecithin (lysolecithin group), and group 3 included eight rats with lesions that were injected with lysolecithin and received VitD (VitD group). We analyzed neurogenesis both in the subventricular zone and at the lesion site.
    Results: Administration of VitD promotes the proliferation and differentiation of neural stem cells in the subventricular zone and the migration of these cells to the lesion site in the corpus callosum; these cells subsequently differentiate into oligodendrocyte lineage cells and produce myelin basic protein. This phenomenon was not caused by microglial activation, which was less marked in rats receiving VitD. Megalin expression did not increase at the lesion site, which suggests that VitD is internalized by other mechanisms.
    Conclusion: Our results support the hypothesis that regardless of the presence of VitD deficiency, treatment with VitD may contribute to remyelination by promoting the proliferation of oligodendrocyte precursor cells.
    MeSH term(s) Animals ; Cell Differentiation/drug effects ; Cell Differentiation/physiology ; Cell Lineage/drug effects ; Male ; Multiple Sclerosis/therapy ; Neural Stem Cells/physiology ; Oligodendroglia/physiology ; Rats ; Rats, Wistar ; Remyelination/drug effects ; Remyelination/physiology ; Treatment Outcome ; Vitamin D/metabolism ; Vitamin D/pharmacology ; Vitamins/metabolism ; Vitamins/pharmacology
    Chemical Substances Vitamins ; Vitamin D (1406-16-2)
    Language English
    Publishing date 2019-12-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2623587-0
    ISSN 2162-3279 ; 2162-3279
    ISSN (online) 2162-3279
    ISSN 2162-3279
    DOI 10.1002/brb3.1498
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  8. Article ; Online: Intranasal Administration of Undifferentiated Oligodendrocyte Lineage Cells as a Potential Approach to Deliver Oligodendrocyte Precursor Cells into Brain.

    Gómez-Pinedo, Ulises / Matías-Guiu, Jordi A / Benito-Martín, María Soledad / Moreno-Jiménez, Lidia / Sanclemente-Alamán, Inmaculada / Selma-Calvo, Belen / Pérez-Suarez, Sara / Sancho-Bielsa, Francisco / Canales-Aguirre, Alejandro / Mateos-Díaz, Juan Carlos / Hernández-Sapiéns, Mercedes A / Reza-Zaldívar, Edwin E / Ojeda-Hernández, Doddy Denise / Vidorreta-Ballesteros, Lucía / Montero-Escribano, Paloma / Matías-Guiu, Jorge

    International journal of molecular sciences

    2021  Volume 22, Issue 19

    Abstract: Oligodendrocyte precursor cell (OPC) migration is a mechanism involved in remyelination; these cells migrate from niches in the adult CNS. However, age and disease reduce the pool of OPCs; as a result, the remyelination capacity of the CNS decreases over ...

    Abstract Oligodendrocyte precursor cell (OPC) migration is a mechanism involved in remyelination; these cells migrate from niches in the adult CNS. However, age and disease reduce the pool of OPCs; as a result, the remyelination capacity of the CNS decreases over time. Several experimental studies have introduced OPCs to the brain via direct injection or intrathecal administration. In this study, we used the nose-to brain pathway to deliver oligodendrocyte lineage cells (human oligodendroglioma (HOG) cells), which behave similarly to OPCs in vitro. To this end, we administered GFP-labelled HOG cells intranasally to experimental animals, which were subsequently euthanised at 30 or 60 days. Our results show that the intranasal route is a viable route to the CNS and that HOG cells administered intranasally migrate preferentially to niches of OPCs (clusters created during embryonic development and adult life). Our study provides evidence, albeit limited, that HOG cells either form clusters or adhere to clusters of OPCs in the brains of experimental animals.
    MeSH term(s) Administration, Intranasal ; Animals ; Brain/cytology ; Brain/physiology ; Cell Differentiation ; Cells, Cultured ; Demyelinating Diseases/therapy ; Humans ; Oligodendrocyte Precursor Cells/cytology ; Oligodendroglioma/chemistry ; Remyelination ; Stem Cells/cytology
    Language English
    Publishing date 2021-10-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms221910738
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  9. Article ; Online: Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2

    Sanclemente-Alaman, Inmaculada / Moreno-Jiménez, Lidia / Benito-Martín, María Soledad / Canales-Aguirre, Alejandro / Matías-Guiu, Jordi A. / Matías-Guiu, Jorge / Gómez-Pinedo, Ulises

    Frontiers in Immunology

    2020  Volume 11

    Keywords covid19
    Publisher Frontiers Media SA
    Publishing country ch
    Document type Article ; Online
    ZDB-ID 2606827-8
    ISSN 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2020.02163
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  10. Article: Experimental Models for the Study of Central Nervous System Infection by SARS-CoV-2

    Sanclemente-Alaman, Inmaculada / Moreno-Jiménez, Lidia / Benito-Martín, María Soledad / Canales-Aguirre, Alejandro / Matías-Guiu, Jordi A / Matías-Guiu, Jorge / Gómez-Pinedo, Ulises

    Front Immunol

    Abstract: Introduction: The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic ... ...

    Abstract Introduction: The response to the SARS-CoV-2 coronavirus epidemic requires increased research efforts to expand our knowledge of the disease. Questions related to infection rates and mechanisms, the possibility of reinfection, and potential therapeutic approaches require us not only to use the experimental models previously employed for the SARS-CoV and MERS-CoV coronaviruses but also to generate new models to respond to urgent questions. Development: We reviewed the different experimental models used in the study of central nervous system (CNS) involvement in COVID-19 both in different cell lines that have enabled identification of the virus' action mechanisms and in animal models (mice, rats, hamsters, ferrets, and primates) inoculated with the virus. Specifically, we reviewed models used to assess the presence and effects of SARS-CoV-2 on the CNS, including neural cell lines, animal models such as mouse hepatitis virus CoV (especially the 59 strain), and the use of brain organoids. Conclusion: Given the clear need to increase our understanding of SARS-CoV-2, as well as its potential effects on the CNS, we must endeavor to obtain new information with cellular or animal models, with an appropriate resemblance between models and human patients.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #776209
    Database COVID19

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