{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:29:37Z","timestamp":1791815377439,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T00:00:00Z","timestamp":1444176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"German Research Foundation within the framework of the Munich Cluster for Systems Neurology (EXC 1010 SyNergy)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), the most common inherited small\u2010vessel disease, is associated with vascular aggregation of mutant Notch3 protein, dysfunction of cerebral vessels, and dementia. Pericytes, perivascular cells involved in microvascular function, express Notch3. Therefore, we hypothesize that these cells may play a role in the pathogenesis of CADASIL.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Two\u2010, 7\u2010, and 12\u2010month\u2010old CADASIL mutant mice (TgNotch3\n                      <jats:sup>R169C<\/jats:sup>\n                      ) and wild\u2010type controls were examined regarding Notch3 aggregation in pericytes, the coverage of cerebral vessels by pericytes, pericyte numbers, capillary density, blood\u2013brain barrier (BBB) integrity, astrocytic end\u2010feet, and the expression of astrocytic gap junction and endothelial adherens junction protein using immunostaining and Western blot analysis. In addition, we examined cerebrovascular CO\n                      <jats:sub>2<\/jats:sub>\n                      reactivity using laser Doppler fluxmetry and in vivo microscopy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      With increasing age, mutated Notch3 aggregated around pericytes and smooth muscle cells. Notch3 aggregation caused significant reduction of pericyte number and coverage of capillaries by pericyte processes (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.01). These changes were associated with detachment of astrocytic end\u2010feet from cerebral microvessels, leakage of plasma proteins, reduction in expression of endothelial adherens junction protein, and reduced microvascular reactivity to CO\n                      <jats:sub>2<\/jats:sub>\n                      . Smooth muscle cells were not affected by Notch3 accumulation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our results show that pericytes are the first cells affected by Notch3 aggregation in CADASIL mice. Pericyte pathology causes opening of the BBB and microvascular dysfunction. Therefore, protecting pericytes may represent a novel therapeutic strategy for vascular dementia. Ann Neurol 2015;78:887\u2013900<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.24512","type":"journal-article","created":{"date-parts":[[2015,8,27]],"date-time":"2015-08-27T19:48:51Z","timestamp":1440704931000},"page":"887-900","source":"Crossref","is-referenced-by-count":161,"title":["Pericytes are involved in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy"],"prefix":"10.1002","volume":"78","author":[{"given":"Mitrajit","family":"Ghosh","sequence":"first","affiliation":[{"name":"Institute for Stroke and Dementia Research University of Munich Medical Center, Ludwig Maximilian University  Munich"},{"name":"Experimental Neurosurgery, Department of Neurosurgery Rechts der Isar Hospital, Technical University Munich  Munich"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilde","family":"Balbi","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research University of Munich Medical Center, Ludwig Maximilian University  Munich"},{"name":"Graduate School of Systemic Neurosciences Ludwig Maximilian University  Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farida","family":"Hellal","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research University of Munich Medical Center, Ludwig Maximilian University  Munich"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Dichgans","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research University of Munich Medical Center, Ludwig Maximilian University  Munich"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Lindauer","sequence":"additional","affiliation":[{"name":"Experimental Neurosurgery, Department of Neurosurgery Rechts der Isar Hospital, Technical University Munich  Munich"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich"},{"name":"Translational Neurosurgery and Neurobiology, Department of Neurosurgery Medical Faculty, RWTH Aachen University Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Plesnila","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research University of Munich Medical Center, Ludwig Maximilian University  Munich"},{"name":"Munich Cluster for Systems Neurology (SyNergy)  Munich"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,10,7]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"1729","article-title":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy: a positron emission tomography study in two affected family members","volume":"26","author":"Chabriat H","year":"1995","journal-title":"Stroke"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410440506"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(09)70127-9"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/383707a0"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI39733"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000245091.28429.6a"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.09.013"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182749f39"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.09.043"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2946"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/bpa.12004"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09522"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2011.07.001"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1011321108"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13165"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.01.003"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2011.01290.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.3109\/01913123.2011.620220"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/neu.2009.1114"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2006.07.016"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-10-32"},{"key":"e_1_2_8_23_1","first-page":"909","article-title":"Pericytes. 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