Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain
Diverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervou...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Cellular Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1125109/full |
| _version_ | 1797871441637539840 |
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| author | Héctor Hernández-Parra Héctor Hernández-Parra Octavio Daniel Reyes-Hernández Gabriela Figueroa-González Manuel González-Del Carmen Maykel González-Torres Sheila I. Peña-Corona Benjamín Florán Hernán Cortés Gerardo Leyva-Gómez |
| author_facet | Héctor Hernández-Parra Héctor Hernández-Parra Octavio Daniel Reyes-Hernández Gabriela Figueroa-González Manuel González-Del Carmen Maykel González-Torres Sheila I. Peña-Corona Benjamín Florán Hernán Cortés Gerardo Leyva-Gómez |
| author_sort | Héctor Hernández-Parra |
| collection | DOAJ |
| description | Diverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervous System (CNS). This mini-review discusses the main proposed mechanisms by which SARS-CoV-2 interacts with the blood-brain barrier (BBB) and its involvement in the passage of drugs into the CNS. We performed a search in PubMed with the terms “COVID-19” or “SARS-CoV-2” and “blood-brain barrier injury” or “brain injury” from the year 2019 to 2022. We found proposed evidence that SARS-CoV-2 infects neurovascular cells and increases BBB permeability by increasing the expression of matrix metalloproteinase-9 that degrades type IV collagen in the basement membrane and through activating RhoA, which induces restructuring of the cytoskeleton and alters the integrity of the barrier. The breakdown of the BBB triggers a severe inflammatory response, causing the cytokine storm (release of IL-1β, IL-6, TNF-α, etc.) characteristic of the severe phase of COVID-19, which includes the recruitment of macrophages and lymphocytes and the activation of astrocytes and microglia. We conclude that the increased permeability of the BBB would allow the passage of drugs that would not reach the brain in a normal physiological state, thus enhancing certain drugs’ beneficial or adverse effects. We hope this article will encourage research on the impact of drugs on patients with COVID-19 and recovered patients with sequelae, focusing mainly on possible dose adjustments and changes in pharmacokinetic parameters. |
| first_indexed | 2024-04-10T00:44:07Z |
| format | Article |
| id | doaj.art-91883d3d107c4b19975ce6057c9d6606 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-10T00:44:07Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-91883d3d107c4b19975ce6057c9d66062023-03-14T04:31:37ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-03-011710.3389/fncel.2023.11251091125109Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brainHéctor Hernández-Parra0Héctor Hernández-Parra1Octavio Daniel Reyes-Hernández2Gabriela Figueroa-González3Manuel González-Del Carmen4Maykel González-Torres5Sheila I. Peña-Corona6Benjamín Florán7Hernán Cortés8Gerardo Leyva-Gómez9Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, MexicoDepartamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, MexicoLaboratorio de Biología Molecular del Cáncer, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México, MexicoLaboratorio de Farmacogenética, UMIEZ, Facultad de Estudios Superiores Zaragoza, Universidad Nacional Autónoma de México, Ciudad de México, MexicoFacultad de Medicina, Universidad Veracruzana, Heroica Veracruz, MexicoConacyt and Laboratorio de Biotecnología, Instituto Nacional de Rehabilitación “Luís Guillermo Ibarra”, Ciudad de Mexico, MexicoDepartamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, MexicoDepartamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico City, MexicoLaboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, MexicoDepartamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, MexicoDiverse neurological symptoms have been reported in patients with SARS-CoV-2 disease (COVID-19), including stroke, ataxia, meningitis, encephalitis, and cognitive impairment. These alterations can cause serious sequelae or death and are associated with the entry of SARS-CoV-2 into the Central Nervous System (CNS). This mini-review discusses the main proposed mechanisms by which SARS-CoV-2 interacts with the blood-brain barrier (BBB) and its involvement in the passage of drugs into the CNS. We performed a search in PubMed with the terms “COVID-19” or “SARS-CoV-2” and “blood-brain barrier injury” or “brain injury” from the year 2019 to 2022. We found proposed evidence that SARS-CoV-2 infects neurovascular cells and increases BBB permeability by increasing the expression of matrix metalloproteinase-9 that degrades type IV collagen in the basement membrane and through activating RhoA, which induces restructuring of the cytoskeleton and alters the integrity of the barrier. The breakdown of the BBB triggers a severe inflammatory response, causing the cytokine storm (release of IL-1β, IL-6, TNF-α, etc.) characteristic of the severe phase of COVID-19, which includes the recruitment of macrophages and lymphocytes and the activation of astrocytes and microglia. We conclude that the increased permeability of the BBB would allow the passage of drugs that would not reach the brain in a normal physiological state, thus enhancing certain drugs’ beneficial or adverse effects. We hope this article will encourage research on the impact of drugs on patients with COVID-19 and recovered patients with sequelae, focusing mainly on possible dose adjustments and changes in pharmacokinetic parameters.https://www.frontiersin.org/articles/10.3389/fncel.2023.1125109/fullblood-brain barrierdrug permeationcentral nervous systemCOVID-19immune response |
| spellingShingle | Héctor Hernández-Parra Héctor Hernández-Parra Octavio Daniel Reyes-Hernández Gabriela Figueroa-González Manuel González-Del Carmen Maykel González-Torres Sheila I. Peña-Corona Benjamín Florán Hernán Cortés Gerardo Leyva-Gómez Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain Frontiers in Cellular Neuroscience blood-brain barrier drug permeation central nervous system COVID-19 immune response |
| title | Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain |
| title_full | Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain |
| title_fullStr | Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain |
| title_full_unstemmed | Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain |
| title_short | Alteration of the blood-brain barrier by COVID-19 and its implication in the permeation of drugs into the brain |
| title_sort | alteration of the blood brain barrier by covid 19 and its implication in the permeation of drugs into the brain |
| topic | blood-brain barrier drug permeation central nervous system COVID-19 immune response |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1125109/full |
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