PhD Scientific Days 2025

Budapest, 7-9 July 2025

Poster Session III. - R: Neurosciences

Role of Brain Vascular Senescence in Age-related Cerebromicrovascular Dysfunction and Vascular Cognitive Impairment

Name of the presenter

Csík Boglárka

Institute/workplace of the presenter

Institute of Preventive Medicine and Public Health

Authors

Boglárka Csík1,2,3,4, Ádám Nyúl-Tóth1,3,4, Roland Patai3,4, Rafał Gulej3,4, Siva Sai Chandragiri3,4, Raghavendra Yelahanka Nagaraja3,4, Stefano Tarantini1,3,4, Santny Shanmugarama3,4, Anna Csiszár3,4, Zoltan Ungvári1,3,4

1: Institute of Preventive Medicine and Public Health, Faculty of Medicine, Semmelweis University, Budapest, Hungary
2: Health Sciences Program, Doctoral College, Semmelweis University, Budapest, Hungary.
3: Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, OUHSC, Oklahoma City, OK, USA
4: Oklahoma Center for Geroscience and Healthy Brain Aging, OUHSC, Oklahoma City, OK, USA

Text of the abstract

Background: With advanced age, cerebromicrovascular (CMV) dysfunctions—such as blood-brain-barrier (BBB) disruption, microvascular rarefaction and impaired neurovascular coupling (NVC)—contribute to the development of vascular cognitive impairment (VCID) and even Alzheimer's disease (AD). Our previous research established a link between vascular senescence-induced CMV dysfunction and cognitive decline in accelerated aging models.
Aims: The objective of this study was to determine the timeline of age-related accumulation of senescent endothelial cells and their role in neurovascular dysfunction, microvascular rarefaction, BBB disruption, and cognitive decline.
Methods and Material: Transgenic p16-3MR mice were treated with senolytic therapy, allowing for the selective elimination of senescent cells. The p16-3MR model enables both the detection and depletion of senescent cells using Ganciclovir. Mice underwent multiple anatomical and functional assessments, including NVC measurements via laser speckle flowmetry, microvascular density evaluation and BBB permeability analysis using two-photon microscopy as well as spatial learning and memory performance assessment using the radial arm water maze.
Results: Aging led to increased microvascular endothelial cell senescence, which was associated with impaired NVC responses, microvascular rarefaction, and BBB disruption. These changes correlated with cognitive decline in aged mice. Senolytic treatment in 18–19-month-old mice significantly reduced endothelial senescence, restored NVC responses, partially improved BBB integrity, and enhanced cognitive function.
Conclusion: Our findings demonstrate that targeting senescent endothelial cells can restore key neurovascular functions and improve cognitive outcomes in aging. Importantly, these results highlight the therapeutic potential of senolytic strategies in preventing or delaying cerebrovascular aging, which could have implications for early intervention in VCID.
Funding: AHA916225, AHA834339, RF1AG072295, R01AG055395, R01AG068295; R01AG070915, K01AG073614, R01NS100782, P30AG050911, P20GM125528