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000285728 1001_ $$0P:(DE-2719)9000797$$aArndt, Philipp$$b0$$eFirst author
000285728 245__ $$aVascular and Neural Transcriptomics Reveal Stage-Dependent Pathways to Inflammation and Cognitive Dysfunction in a Rat Model of Hypertension.
000285728 260__ $$aNew York, NY$$bAssociation$$c2026
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000285728 520__ $$aChronic 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.
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000285728 650_7 $$2Other$$a18F‐FDG PET
000285728 650_7 $$2Other$$aRNA sequencing
000285728 650_7 $$2Other$$aSHRSP
000285728 650_7 $$2Other$$acerebral small‐vessel disease
000285728 650_7 $$2Other$$ahypertension
000285728 650_2 $$2MeSH$$aAnimals
000285728 650_2 $$2MeSH$$aHypertension: genetics
000285728 650_2 $$2MeSH$$aHypertension: complications
000285728 650_2 $$2MeSH$$aHypertension: metabolism
000285728 650_2 $$2MeSH$$aHypertension: physiopathology
000285728 650_2 $$2MeSH$$aDisease Models, Animal
000285728 650_2 $$2MeSH$$aRats, Inbred SHR
000285728 650_2 $$2MeSH$$aTranscriptome
000285728 650_2 $$2MeSH$$aRats
000285728 650_2 $$2MeSH$$aCognitive Dysfunction: genetics
000285728 650_2 $$2MeSH$$aCognitive Dysfunction: metabolism
000285728 650_2 $$2MeSH$$aCognitive Dysfunction: etiology
000285728 650_2 $$2MeSH$$aCognitive Dysfunction: physiopathology
000285728 650_2 $$2MeSH$$aMale
000285728 650_2 $$2MeSH$$aFrontal Lobe: metabolism
000285728 650_2 $$2MeSH$$aFrontal Lobe: blood supply
000285728 650_2 $$2MeSH$$aInflammation: genetics
000285728 650_2 $$2MeSH$$aInflammation: metabolism
000285728 650_2 $$2MeSH$$aBehavior, Animal
000285728 650_2 $$2MeSH$$aMicroglia: metabolism
000285728 650_2 $$2MeSH$$aBlood-Brain Barrier: metabolism
000285728 650_2 $$2MeSH$$aBlood Pressure
000285728 7001_ $$00000-0002-3957-3848$$aMorton, Lorena$$b1
000285728 7001_ $$00000-0001-7137-8260$$aBriese, Michael$$b2
000285728 7001_ $$00009-0003-2096-4640$$aLämmlin, Naomi$$b3
000285728 7001_ $$0P:(DE-2719)9002178$$aMattern, Hendrik$$b4
000285728 7001_ $$0P:(DE-HGF)0$$aHasanuzzaman, Md$$b5
000285728 7001_ $$0P:(DE-2719)9001696$$aWesthues, Melina Julia$$b6
000285728 7001_ $$0P:(DE-2719)2814351$$aKhoshneviszadeh, Mahsima$$b7
000285728 7001_ $$00000-0002-5472-8692$$aAppenzeller, Silke$$b8
000285728 7001_ $$00000-0001-9743-2325$$aGündel, Daniel$$b9
000285728 7001_ $$00000-0002-1136-3857$$aToussaint, Magali$$b10
000285728 7001_ $$00000-0001-5555-7058$$aBrust, Peter$$b11
000285728 7001_ $$00000-0002-4107-3455$$aKniess, Torsten$$b12
000285728 7001_ $$0P:(DE-2719)2811208$$aOelschlegel, Anja$$b13
000285728 7001_ $$aGoldschmidt, Jürgen$$b14
000285728 7001_ $$00000-0003-2571-3501$$aMeuth, Sven$$b15
000285728 7001_ $$0P:(DE-2719)2811487$$aMüller, Patrick$$b16$$udzne
000285728 7001_ $$00000-0003-3888-6532$$aBraun-Dullaeus, Rüdiger$$b17
000285728 7001_ $$0P:(DE-2719)9000903$$aDebska-Vielhaber, Grazyna$$b18
000285728 7001_ $$0P:(DE-2719)2000035$$aVielhaber, Stefan$$b19$$udzne
000285728 7001_ $$aBecker, Axel$$b20
000285728 7001_ $$0P:(DE-2719)2810577$$aDityatev, Alexander$$b21
000285728 7001_ $$0P:(DE-2719)2813348$$aHenneicke, Solveig$$b22
000285728 7001_ $$00000-0002-4737-2974$$aSendtner, Michael$$b23
000285728 7001_ $$00000-0002-9900-8605$$aDunay, Ildiko$$b24
000285728 7001_ $$0P:(DE-2719)2812631$$aSchreiber, Stefanie$$b25$$eLast author
000285728 773__ $$0PERI:(DE-600)2653953-6$$a10.1161/JAHA.125.040710$$gVol. 15, no. 6, p. e040710$$n6$$pe040710$$tJournal of the American Heart Association$$v15$$x2047-9980$$y2026
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