Cargando…
Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research
Subcortical ischemic white matter injury (SIWMI), pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging, is a common cause of cognitive decline in elderly. Despite its high prevalence, it remains unknown how various components of the white matter dege...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wolters Kluwer - Medknow
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067929/ https://www.ncbi.nlm.nih.gov/pubmed/33063714 http://dx.doi.org/10.4103/1673-5374.295313 |
_version_ | 1783682917612912640 |
---|---|
author | Cui, Yuexian Jin, Xuelian Choi, Jun Young Kim, Byung Gon |
author_facet | Cui, Yuexian Jin, Xuelian Choi, Jun Young Kim, Byung Gon |
author_sort | Cui, Yuexian |
collection | PubMed |
description | Subcortical ischemic white matter injury (SIWMI), pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging, is a common cause of cognitive decline in elderly. Despite its high prevalence, it remains unknown how various components of the white matter degenerate in response to chronic ischemia. This incomplete knowledge is in part due to a lack of adequate animal model. The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components. The SIWMI animal models are categorized into 1) chemically induced SIWMI models, 2) vascular occlusive SIWMI models, and 3) SIWMI models with comorbid vascular risk factors. Chemically induced models display consistent lesions in predetermined areas of the white matter, but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities. Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified. When combined with comorbid vascular risk factors (specifically hypertension), however, they can produce progressive and definitive white matter lesions including diffuse rarefaction, demyelination, loss of oligodendrocytes, and glial activation, which are by far the closest to those found in human white matter hyperintensities lesions. However, considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models. In the meantime, in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury. Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities. |
format | Online Article Text |
id | pubmed-8067929 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Wolters Kluwer - Medknow |
record_format | MEDLINE/PubMed |
spelling | pubmed-80679292021-04-27 Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research Cui, Yuexian Jin, Xuelian Choi, Jun Young Kim, Byung Gon Neural Regen Res Review Subcortical ischemic white matter injury (SIWMI), pathological correlate of white matter hyperintensities or leukoaraiosis on magnetic resonance imaging, is a common cause of cognitive decline in elderly. Despite its high prevalence, it remains unknown how various components of the white matter degenerate in response to chronic ischemia. This incomplete knowledge is in part due to a lack of adequate animal model. The current review introduces various SIWMI animal models and aims to scrutinize their advantages and disadvantages primarily in regard to the pathological manifestations of white matter components. The SIWMI animal models are categorized into 1) chemically induced SIWMI models, 2) vascular occlusive SIWMI models, and 3) SIWMI models with comorbid vascular risk factors. Chemically induced models display consistent lesions in predetermined areas of the white matter, but the abrupt evolution of lesions does not appropriately reflect the progressive pathological processes in human white matter hyperintensities. Vascular occlusive SIWMI models often do not exhibit white matter lesions that are sufficiently unequivocal to be quantified. When combined with comorbid vascular risk factors (specifically hypertension), however, they can produce progressive and definitive white matter lesions including diffuse rarefaction, demyelination, loss of oligodendrocytes, and glial activation, which are by far the closest to those found in human white matter hyperintensities lesions. However, considerable surgical mortality and unpredictable natural deaths during a follow-up period would necessitate further refinements in these models. In the meantime, in vitro SIWMI models that recapitulate myelinated white matter track may be utilized to study molecular mechanisms of the ischemic white matter injury. Appropriate in vivo and in vitro SIWMI models will contribute in a complementary manner to making a breakthrough in developing effective treatment to prevent progression of white matter hyperintensities. Wolters Kluwer - Medknow 2020-10-09 /pmc/articles/PMC8067929/ /pubmed/33063714 http://dx.doi.org/10.4103/1673-5374.295313 Text en Copyright: © 2021 Neural Regeneration Research https://creativecommons.org/licenses/by-nc-sa/4.0/This is an open access journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms. |
spellingShingle | Review Cui, Yuexian Jin, Xuelian Choi, Jun Young Kim, Byung Gon Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
title | Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
title_full | Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
title_fullStr | Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
title_full_unstemmed | Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
title_short | Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
title_sort | modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067929/ https://www.ncbi.nlm.nih.gov/pubmed/33063714 http://dx.doi.org/10.4103/1673-5374.295313 |
work_keys_str_mv | AT cuiyuexian modelingsubcorticalischemicwhitematterinjuryinrodentsunmetneedforabreakthroughintranslationalresearch AT jinxuelian modelingsubcorticalischemicwhitematterinjuryinrodentsunmetneedforabreakthroughintranslationalresearch AT choijunyoung modelingsubcorticalischemicwhitematterinjuryinrodentsunmetneedforabreakthroughintranslationalresearch AT kimbyunggon modelingsubcorticalischemicwhitematterinjuryinrodentsunmetneedforabreakthroughintranslationalresearch |