{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T05:55:08Z","timestamp":1775282108679,"version":"3.50.1"},"reference-count":56,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"10_suppl_1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2010,10]]},"abstract":"<jats:p>\n            Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) syndrome is the most common monogenic inherited form of small vessel disease, characterized by frequent migraine attacks with aura, recurrent strokes and progressive white matter degeneration. Early vascular cognitive impairment progresses into frank dementia of subcortical type later in life. Linked to mutations in the\n            <jats:italic>NOTCH3<\/jats:italic>\n            gene, CADASIL vasculopathy is associated with accumulation of granular osmiophilic material and NOTCH3 extracellular domain around small caliber arteries and arterioles, and eventual loss of vascular smooth muscle cells. Cerebral blood flow dysregulation has been hypothesized as a major mechanism, largely based on evidence from hemodynamic studies in CADASIL patients. Although animal models expressing CADASIL mutations reproduced the pathology and cerebrovascular dysfunction, the phenotypic spectrum has been quite heterogeneous, possibly due to the choice of genetic constructs and obvious species differences between mouse and man. Nevertheless, these experimental models provide new opportunities to explore the molecular and physiological mechanisms of CADASIL, and address the fundamental question of whether CADASIL phenotype represents loss of NOTCH3 function or gain of a novel and pathological function. Here, I provide an overview of existing animal models of CADASIL and the pathophysiological insights gained from these models.\n          <\/jats:p>","DOI":"10.1161\/strokeaha.110.595207","type":"journal-article","created":{"date-parts":[[2010,9,27]],"date-time":"2010-09-27T23:23:07Z","timestamp":1285629787000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["CADASIL"],"prefix":"10.1161","volume":"41","author":[{"given":"Cenk","family":"Ayata","sequence":"first","affiliation":[{"name":"From the Neurovascular Research Laboratory, Department of Radiology, and Stroke Service and Neuroscience Intensive Care Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Mass."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/383707a0"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng0393-256"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70127-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000048162.16852.88"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.109.568402"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000265221.05610.70"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000257968.24015.bf"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.57.6.1066"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000245091.28429.6a"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn364"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000032620.91848.1c"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/strokeaha.108.528299"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2004.tb00078.x"},{"key":"e_1_3_2_14_2","first-page":"1268","volume":"22","year":"2001","unstructured":"Bruening R, Dichgans M, Berchtenbreiter C, Yousry T, Seelos KC, Wu RH, Mayer M, Brix G, Reiser M. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: decrease in regional cerebral blood volume in hyperintense subcortical lesions inversely correlates with disability and cognitive performance. 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The archetypal r90c cadasil-notch3 mutation retains notch3 function in vivo. 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