title: Spontaneous white matter lesion in brain of stroke-prone renovascular hypertensive rats: a study from MRI, pathology and behavior.
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.
authors.affiliation: Department 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.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Medicine and Therapeutics, Chinese University of Hongkong, Hongkong, China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Lan
authors.affiliation: Department 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.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department 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.
authors.forename: Xiaotan
authors.initials: X
authors.lastname: Ji
authors.affiliation: Department 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.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department 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.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department 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.
authors.forename: Ruxun
authors.initials: R
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, China. sunjian@sysucc.org.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000473:pathology / Q000648:ultrastructure; D049109:Cell Proliferation; D059345:Cerebral Small Vessel Diseases / Q000235:genetics / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D003071:Cognition / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D008279:Magnetic Resonance Imaging; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009186:Myelin Sheath / Q000473:pathology; D009412:Nerve Fibers / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000235:genetics* / Q000473:pathology*; D066127:White Matter / Q000473:pathology*
keywords: Animal model; Cognition; Small vessel disease; Stroke-prone renovascular hypertensive rats (RHRSP); White matter lesion (WML)