TY  - JOUR
AU  - Schreiber, Stefanie
AU  - Ulbrich, Philipp
AU  - Morton, Lorena
AU  - Garza, Alejandra P
AU  - Müller, Patrick
AU  - Neumann, Katja
AU  - Mattern, Hendrik
AU  - Dörner, Marc
AU  - Bernal, Jose
AU  - Vielhaber, Stefan
AU  - Meuth, Sven G
AU  - Dunay, Ildiko R
AU  - Dityatev, Alexander
AU  - Henneicke, Solveig
TI  - Immune system activation and cognitive impairment in arterial hypertension.
JO  - American journal of physiology / Cell physiology
VL  - 327
IS  - 6
SN  - 0363-6143
CY  - Bethesda, Md.
PB  - American Physiological Society
M1  - DZNE-2024-01389
SP  - C1577 - C1590
PY  - 2024
AB  - 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 prohypertensive stimuli induce mechanical stress and systemic inflammatory responses that shift peripheral and meningeal immune effector mechanisms toward a proinflammatory 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.
KW  - Humans
KW  - Hypertension: immunology
KW  - Hypertension: physiopathology
KW  - Cognitive Dysfunction: immunology
KW  - Cognitive Dysfunction: physiopathology
KW  - Animals
KW  - Blood-Brain Barrier: immunology
KW  - Brain: immunology
KW  - Brain: physiopathology
KW  - Brain: metabolism
KW  - Brain: pathology
KW  - Immune System: immunology
KW  - Immune System: physiopathology
KW  - Immune System: metabolism
KW  - Cognition: physiology
KW  - Inflammation: immunology
KW  - arterial hypertension (Other)
KW  - cerebral small vessel disease (Other)
KW  - cognitive impairment (Other)
KW  - cytokines (Other)
KW  - immune system (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39495252
DO  - DOI:10.1152/ajpcell.00219.2024
UR  - https://pub.dzne.de/record/273915
ER  -