| Autor: |
Schreiber S; Department of Neurology, University Hospital Magdeburg, Magdeburg, Germany., Arndt P; Department of Neurology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany., Morton L; Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, Germany., Garza AP; Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, Germany., Müller P; Cardiology & Angiology, University Hospital Magdeburg, Magdeburg, Germany., Neumann K; Neurology, University Hospital Magdeburg, Magdeburg, Germany., Mattern H; Biomedical Magnetic Resonance, Faculty of Natural Sciences, Otto-von-Guericke University Magdeburg, Magdeburg, Germany., Dörner M; Department of Consultation-Liaison-Psychiatry and Psychosomatic Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland., Bernal J; Institute of Cognitive Neurology and Dementia Research (IKND), Otto-von-Guericke University Magdeburg, Magdeburg, Germany., Vielhaber S; Neurology, University Hospital Magdeburg, Magdeburg, Germany., Meuth SG; Neurology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany., Dunay IR; Institute of Inflammation and Neurodegeneration, Otto von Guericke University Magdeburg, Magdeburg, Germany., Dityatev A; German Center for Neurodegenerative Diseases, Germany., Henneicke S; Neurology, University Hospital Magdeburg, Magdeburg, Germany. |
| Abstrakt: |
Chronic arterial hypertension disrupts the integrity of the cerebral microvasculature, doubling the risk of age-related dementia. Despite sufficient antihypertensive therapy, in still a significant proportion of individuals blood pressure lowering alone does not preserve cognitive health. Accumulating evidence highlights the role of inflammatory mechanisms in the pathogenesis of hypertension. In this review, we introduce a temporal framework to explore how early immune system activation and interactions at neurovascular-immune interfaces pave the way to cognitive impairment. The overall paradigm suggests that pro-hypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms towards a pro-inflammatory state. Neurovascular-immune interfaces in the brain include a dysfunctional blood-brain barrier, crossed by peripheral immune cells; the perivascular space, in which macrophages respond to cerebrospinal fluid- and blood-derived immune regulators; and the meningeal immune reservoir, particularly T cells. Immune responses at these interfaces bridge peripheral and neurovascular unit inflammation, directly contributing to impaired brain perfusion, clearance of toxic metabolites and synaptic function. We propose that deep immunophenotyping in biofluids together with advanced neuroimaging could aid in the translational determination of sequential immune and brain endotypes specific to arterial hypertension. This could close knowledge gaps on how and when immune system activation transits into neurovascular dysfunction and cognitive impairment. In the future, targeting specific immune mechanisms could prevent and halt hypertension disease progression before clinical symptoms arise, addressing the need for new interventions against one of the leading threats to cognitive health. |
