中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 638-642.doi: 10.4103/1673-5374.295313

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

啮齿动物的皮质下缺血性白质损伤建模:未满足转化研究突破的需求

  

  • 出版日期:2021-04-15 发布日期:2020-12-21

Modeling subcortical ischemic white matter injury in rodents: unmet need for a breakthrough in translational research

Yuexian Cui1, 2, 4, Xuelian Jin1, 2, 5, Jun Young Choi1, 2, 3, *, Byung Gon Kim1, 2, 3, *   

  1. 1 Department of Brain Science, Ajou University School of Medicine, Suwon, Korea;  2 Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, Korea; 3 Department of Neurology, Ajou University School of Medicine, Suwon, Korea;  4 Department of Neurology, Yanbian University Hospital, Yanji, Jilin Province, China;  5 Department of Nephrology, Suqian First Hospital, Suqian, Jiangsu Province, China
  • Online:2021-04-15 Published:2020-12-21
  • Contact: Jun Young Choi, MD, PhD, taz312@gmail.com; Byung Gon Kim, MD, PhD, kimbg@ajou.ac.kr.
  • Supported by:
    This work was supported by the National Research Foundation of Korea (NRF) grants funded by the Korea government (MSIT; Ministry of Science and ICT) (NRF-2018M3A9E8023853 (to JYC), NRF-2018R1C1B6006145 (to JYC), NRF-2018R1A2A1A05020292 (to BGK) and NRF-2019R1A5A2026045 (to JYC and BGK).

摘要: https://orcid.org/0000-0003-2233-9569 (Byung Gon Kim)

Abstract: 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. 

Key words: animal model, axonal degeneration, demyelination, hypertension, ischemia, oligodendrocytes, subcortical ischemic white matter injury, vascular cognitive impairment, white matter hyperintensities