A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease
The selection of an appropriate animal model is key to the production of results with optimal relevance to human disease. Particularly in the case of perinatal brain injury, a dearth of affected human neonatal tissue available for research purposes increases the reliance on animal models for insight...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2810 |
| _version_ | 1797469027676717056 |
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| author | Patricia Renz Andreina Schoeberlein Valérie Haesler Theoni Maragkou Daniel Surbek Amanda Brosius Lutz |
| author_facet | Patricia Renz Andreina Schoeberlein Valérie Haesler Theoni Maragkou Daniel Surbek Amanda Brosius Lutz |
| author_sort | Patricia Renz |
| collection | DOAJ |
| description | The selection of an appropriate animal model is key to the production of results with optimal relevance to human disease. Particularly in the case of perinatal brain injury, a dearth of affected human neonatal tissue available for research purposes increases the reliance on animal models for insight into disease mechanisms. Improvements in obstetric and neonatal care in the past 20 years have caused the pathologic hallmarks of perinatal white matter injury (WMI) to evolve away from cystic necrotic lesions and toward diffuse regions of reactive gliosis and persistent myelin disruption. Therefore, updated animal models are needed that recapitulate the key features of contemporary disease. Here, we report a murine model of acute diffuse perinatal WMI induced through a two-hit inflammatory–hypoxic injury paradigm. Consistent with diffuse human perinatal white matter injury (dWMI), our model did not show the formation of cystic lesions. Corresponding to cellular outcomes of dWMI, our injury protocol produced reactive microgliosis and astrogliosis, disrupted oligodendrocyte maturation, and disrupted myelination.. Functionally, we observed sensorimotor and cognitive deficits in affected mice. In conclusion, we report a novel murine model of dWMI that induces a pattern of brain injury mirroring multiple key aspects of the contemporary human clinical disease scenario. |
| first_indexed | 2024-03-09T19:15:37Z |
| format | Article |
| id | doaj.art-dc9d4a1bf057461dbcc9ab49eb524ed9 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T19:15:37Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-dc9d4a1bf057461dbcc9ab49eb524ed92023-11-24T03:51:05ZengMDPI AGBiomedicines2227-90592022-11-011011281010.3390/biomedicines10112810A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human DiseasePatricia Renz0Andreina Schoeberlein1Valérie Haesler2Theoni Maragkou3Daniel Surbek4Amanda Brosius Lutz5Department for BioMedical Research, University of Bern and Switzerland, 3010 Bern, SwitzerlandDepartment for BioMedical Research, University of Bern and Switzerland, 3010 Bern, SwitzerlandDepartment for BioMedical Research, University of Bern and Switzerland, 3010 Bern, SwitzerlandInstitute of Pathology, University of Bern, 3010 Bern, SwitzerlandDepartment for BioMedical Research, University of Bern and Switzerland, 3010 Bern, SwitzerlandDepartment for BioMedical Research, University of Bern and Switzerland, 3010 Bern, SwitzerlandThe selection of an appropriate animal model is key to the production of results with optimal relevance to human disease. Particularly in the case of perinatal brain injury, a dearth of affected human neonatal tissue available for research purposes increases the reliance on animal models for insight into disease mechanisms. Improvements in obstetric and neonatal care in the past 20 years have caused the pathologic hallmarks of perinatal white matter injury (WMI) to evolve away from cystic necrotic lesions and toward diffuse regions of reactive gliosis and persistent myelin disruption. Therefore, updated animal models are needed that recapitulate the key features of contemporary disease. Here, we report a murine model of acute diffuse perinatal WMI induced through a two-hit inflammatory–hypoxic injury paradigm. Consistent with diffuse human perinatal white matter injury (dWMI), our model did not show the formation of cystic lesions. Corresponding to cellular outcomes of dWMI, our injury protocol produced reactive microgliosis and astrogliosis, disrupted oligodendrocyte maturation, and disrupted myelination.. Functionally, we observed sensorimotor and cognitive deficits in affected mice. In conclusion, we report a novel murine model of dWMI that induces a pattern of brain injury mirroring multiple key aspects of the contemporary human clinical disease scenario.https://www.mdpi.com/2227-9059/10/11/2810perinatal brain injurydiffuse injurywhite matter injurymouse modelgliosismyelination failure |
| spellingShingle | Patricia Renz Andreina Schoeberlein Valérie Haesler Theoni Maragkou Daniel Surbek Amanda Brosius Lutz A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease Biomedicines perinatal brain injury diffuse injury white matter injury mouse model gliosis myelination failure |
| title | A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease |
| title_full | A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease |
| title_fullStr | A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease |
| title_full_unstemmed | A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease |
| title_short | A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease |
| title_sort | novel murine multi hit model of perinatal acute diffuse white matter injury recapitulates major features of human disease |
| topic | perinatal brain injury diffuse injury white matter injury mouse model gliosis myelination failure |
| url | https://www.mdpi.com/2227-9059/10/11/2810 |
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