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@ARTICLE{Arndt:285728,
      author       = {Arndt, Philipp and Morton, Lorena and Briese, Michael and
                      Lämmlin, Naomi and Mattern, Hendrik and Hasanuzzaman, Md
                      and Westhues, Melina Julia and Khoshneviszadeh, Mahsima and
                      Appenzeller, Silke and Gündel, Daniel and Toussaint, Magali
                      and Brust, Peter and Kniess, Torsten and Oelschlegel, Anja
                      and Goldschmidt, Jürgen and Meuth, Sven and Müller,
                      Patrick and Braun-Dullaeus, Rüdiger and Debska-Vielhaber,
                      Grazyna and Vielhaber, Stefan and Becker, Axel and Dityatev,
                      Alexander and Henneicke, Solveig and Sendtner, Michael and
                      Dunay, Ildiko and Schreiber, Stefanie},
      title        = {{V}ascular and {N}eural {T}ranscriptomics {R}eveal
                      {S}tage-{D}ependent {P}athways to {I}nflammation and
                      {C}ognitive {D}ysfunction in a {R}at {M}odel of
                      {H}ypertension.},
      journal      = {Journal of the American Heart Association},
      volume       = {15},
      number       = {6},
      issn         = {2047-9980},
      address      = {New York, NY},
      publisher    = {Association},
      reportid     = {DZNE-2026-00285},
      pages        = {e040710},
      year         = {2026},
      abstract     = {Chronic arterial hypertension causes cerebral microvascular
                      dysfunction and increases dementia risk in aging. However,
                      cognitive health preservation by therapeutic blood pressure
                      lowering alone is limited and depends on disease duration,
                      the degree of irreversible tissue damage, and whether
                      microvascular function can be restored. This study aimed to
                      understand molecular and cellular temporospatial mechanisms
                      of disease in the course of hypertension.We investigated the
                      effects of initial, early chronic and late chronic
                      hypertension in the frontal brain of spontaneously
                      hypertensive stroke-prone rats by applying behavioral tests,
                      histopathology, immunofluorescence, fluorescence-activated
                      cell sorting, microvascular/neural tissue RNA sequencing,
                      and 18F-fluorodeoxyglucose positron emission tomography
                      imaging.Chronic hypertension caused behavioral deficits
                      associated with frontal cortex function. Our results
                      highlight stage-dependent responses to continuous
                      microvascular stress and wounding by hypertension. Early
                      chronic responses included a fast recruitment of activated
                      microglia to the blood vessels, immigration of peripheral
                      immune cells, blood-brain barrier breakdown and an
                      energy-demanding hypermetabolic state. Vascular adaptation
                      mechanisms were observed in later stages and included
                      angiogenesis and upregulation of cellular adhesion molecules
                      and extracellular matrix. Among the top upregulated genes in
                      blood vessels, we identified Igfbp-5, which attenuates
                      protective insulin-like growth factor 1 signaling.Our study
                      provides new insight into mechanisms underlying hypertensive
                      pathobiology and highlights its stage-dependent nature. This
                      groundwork will be helpful for basic and clinical research
                      to identify stage-dependent markers in the human disease
                      course, investigate stage-dependent interventions besides
                      blood pressure lowering, and better understand the
                      relationship between poor vascular health and
                      neurodegenerative diseases.},
      keywords     = {Animals / Hypertension: genetics / Hypertension:
                      complications / Hypertension: metabolism / Hypertension:
                      physiopathology / Disease Models, Animal / Rats, Inbred SHR
                      / Transcriptome / Rats / Cognitive Dysfunction: genetics /
                      Cognitive Dysfunction: metabolism / Cognitive Dysfunction:
                      etiology / Cognitive Dysfunction: physiopathology / Male /
                      Frontal Lobe: metabolism / Frontal Lobe: blood supply /
                      Inflammation: genetics / Inflammation: metabolism /
                      Behavior, Animal / Microglia: metabolism / Blood-Brain
                      Barrier: metabolism / Blood Pressure / 18F‐FDG PET (Other)
                      / RNA sequencing (Other) / SHRSP (Other) / cerebral
                      small‐vessel disease (Other) / hypertension (Other)},
      cin          = {AG Schreiber / AG Dityatev},
      ddc          = {610},
      cid          = {I:(DE-2719)1310010 / I:(DE-2719)1310007},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 351 -
                      Brain Function (POF4-351)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-351},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41294147},
      doi          = {10.1161/JAHA.125.040710},
      url          = {https://pub.dzne.de/record/285728},
}