{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:57:58Z","timestamp":1790618278527,"version":"4.1.0"},"reference-count":56,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To define the critical onset window and mechanisms of white matter lesions (WMLs) in cerebral small vessel disease based on spontaneously hypertensive rat (SHR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>SHRs and age\u2010matched Wistar\u2010Kyoto (WKY) rats were assessed from 20 to 36\u2009weeks of age. Systolic blood pressure, beam\u2010walking performance, and magnetic resonance imaging (MRI)\u2010based white matter changes were evaluated at 4\u2010week intervals. At each time point, randomly selected animals were euthanized for histological analysis. Gait performance and novel object recognition were further assessed at 36\u2009weeks of age. Additional histopathological, neurovascular, neuroinflammatory, transcriptomic, proteomic, and biochemical analyses were performed at the identified critical time point.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SHRs developed sustained hypertension and early small\u2010vessel morphological alterations from 20\u2009weeks, followed by corpus callosum demyelination at 28\u2009weeks and motor, gait, and non\u2010spatial memory deficits by 36\u2009weeks. MRI identified 28\u2009weeks as the onset of detectable white matter microstructural impairment, marked by reduced fractional anisotropy, axial diffusivity, and increased radial diffusivity. At this stage, histological and molecular analyses confirmed myelin disruption, altered mature oligodendrocyte (OL)\u2010 and oligodendrocyte precursor cell (OPC)\u2010associated marker profiles, microvascular rarefaction, blood\u2013brain barrier disruption, and inflammation in SHRs. Transcriptomic analysis highlighted cAMP pathway dysregulation, whereas proteomic analysis identified Pde10a as a significantly upregulated candidate protein. Suppression of downstream cAMP\/PKA\/CREB signaling was further supported by biochemical validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>WMLs emerge at 28\u2009weeks in SHRs and are accompanied by convergent neurovascular injury and inflammatory activation. Pde10a\u2010associated cAMP signaling may represent a candidate mechanism associated with hypertension\u2010related WML development in CSVD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71142","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:31:21Z","timestamp":1789111881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Temporal Mapping of\n                    <scp>CSVD<\/scp>\n                    \u2010Related White Matter Lesions and Concurrent Neurovascular Dysfunction in Spontaneously Hypertensive Rats"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2595-8684","authenticated-orcid":false,"given":"Jing","family":"Peng","sequence":"first","affiliation":[{"name":"Department of Neurology, Dongzhimen Hospital Beijing University of Chinese Medicine  Beijing China"},{"name":"Institute for Brain and Cognitive Disorders 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