A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease.

Renz, Patricia; Schoeberlein, Andreina; Haesler, Valérie; Maragkou, Theoni; Surbek, Daniel; Brosius Lutz, Amanda (2022). A Novel Murine Multi-Hit Model of Perinatal Acute Diffuse White Matter Injury Recapitulates Major Features of Human Disease. Biomedicines, 10(11) MDPI 10.3390/biomedicines10112810

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Gynaecology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pränatale Medizin

UniBE Contributor:

Renz, Patricia Verena; Schoeberlein, Andreina; Haesler, Valérie; Surbek, Daniel and Brosius Lutz, Amanda

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2227-9059

Publisher:

MDPI

Language:

English

Submitter:

Pubmed Import

Date Deposited:

16 Nov 2022 09:10

Last Modified:

05 Dec 2022 16:28

Publisher DOI:

10.3390/biomedicines10112810

PubMed ID:

36359331

Uncontrolled Keywords:

diffuse injury gliosis mouse model myelination failure perinatal brain injury two-hit model white matter injury

BORIS DOI:

10.48350/174766

URI:

https://boris.unibe.ch/id/eprint/174766

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