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Updated: Apr 3, 2026
A Versatile Murine Model of Subcortical White Matter Stroke for the Study of Axonal Degeneration and White Matter Neurobiology
Published on: March 17, 2016
Spontaneous white matter lesion in brain of stroke-prone renovascular hypertensive rats: a study from MRI, pathology
Yuhua Fan1, Linfang Lan2, Lu Zheng3
1Department of Neurology, First Affiliated Hospital Sun Yat-Sen University, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department National Key Discipline, Guangzhou, 510080, China. fansusan@126.com.
Abstract:
Hypertension is considered one of the most important controllable risk factors for white matter lesion (WML). Our previous work found that stroke-prone renovascular hypertensive rats (RHRSP) displayed a high rate of WML. This study aimed to investigate the WML in RHRSP from MRI, pathology and behavior. RHRSP model was established by two-kidney, two-clipmethod and kept for 20 weeks. WML was decteted by magnetic resonance imaging (MRI) and loyez staining. Cognition was tested by morris water maze (MWM). Vascular changes were observed by HE staining on brain and carotid sections. Ultrastucture of blood brain barrier (BBB) were observed by transmission electron microscope. Immunofluorescence was used to detect albumin leakage and cell proliferation. T(2)-weighted MRI scans of RHRSP displayed diffuse, confluent white-matter hyperintensities. Pathological examination of the same rat showed marked vacuoles, disappearence of myelin and nerve fibers in white matter, supporting the neuroimaging findings. Spatial learning and memory impairment were observed in RHRSP. The small arteries in brain exhibited fibrinoid necrosis, hyalinosis and vascular remodeling. BBB disruption and plasma albumin leakage into vascular wall was observed in RHRSP. Increased cell proliferation in subventricular zone was seen in RHRSP. RHRSP demonstrated spontaneous WML and cognitive impairment. Hypertensive small vessel lesions and BBB disruption might paly causative factors for the onset and development of WML. The characteristic features of WML in RHRSP suggested it a valid animal model for WML.
Insights
Hypertension causes white matter lesions (WML). Stroke-prone hypertensive rats developed WML, cognitive deficits, and blood-brain barrier issues, validating them as a WML model.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Pathology
Background:
- Hypertension is a key controllable risk factor for white matter lesions (WML).
- Stroke-prone renovascular hypertensive rats (RHRSP) previously showed a high incidence of WML.
Purpose of the Study:
- To investigate white matter lesions (WML) in RHRSP using MRI, pathology, and behavioral analysis.
- To evaluate RHRSP as a model for studying WML.
Main Methods:
- Established the RHRSP model (two-kidney, two-clip) and observed for 20 weeks.
- Utilized MRI, Lóye staining, HE staining, transmission electron microscopy, and immunofluorescence.
- Assessed cognitive function using the Morris Water Maze (MWM).
Main Results:
- MRI revealed diffuse white matter hyperintensities in RHRSP.
- Pathology confirmed myelin and nerve fiber loss, supporting MRI findings.
- RHRSP exhibited cognitive impairment, vascular damage (necrotic small arteries), blood-brain barrier disruption, and increased cell proliferation.
Conclusions:
- RHRSP spontaneously develop WML and cognitive impairment.
- Hypertensive small vessel disease and blood-brain barrier disruption are potential causes of WML.
- RHRSP serve as a valid animal model for studying WML.
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