# Cerebral microvascular lesions and vascular and neuronal networks

> **NIH NIH RF1** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $50,000

## Abstract

Focal microvascular lesions – such as microinfarcts and microhemorrhages – are frequently observed in the
brains of older individuals and are strongly associated with cognitive impairment and dementia. Yet, the
underlying pathophysiological mechanisms and structural and functional consequences of these lesions are
poorly understood. This proposal aims to unravel the mechanisms underlying microvascular lesion formation
and their impact on local and remote vascular and neuronal networks, in the context of cerebral amyloid
angiopathy (CAA). CAA is one of the most common age-related cerebral small vessel diseases, characterized
by the accumulation of amyloid β in small cortical arterioles. It has been suggested that vascular amyloid
deposition involves a self-reinforcing cycle of vascular smooth muscle cell degeneration and impaired
perivascular clearance of solutes (including amyloid) from the brain, which eventually results in the formation
of microinfarcts and microhemorrhages. Although CAA has traditionally been considered a local disease
resulting in focal lesions from individually affected cortical vessels, recent preliminary observations suggest
profound alterations in surrounding vascular and neuronal networks, with more remote brain tissue injury as a
result. The proposed research will address these network-wide effects of local vascular amyloid accumulation,
by combining advanced neuroimaging and histopathology techniques in ex vivo human brains with cutting-
edge optical imaging tools in living mice. The proposal builds on the applicants’ international leadership in
CAA, their strong background in post-mortem MRI and state-of-the-art histopathology techniques, and
pioneering work in two-photon microscopy of mouse models with CAA. Combined with the world-class
resources and international collaborations with experts in the field to perform advanced image processing, the
proposed set of experiments will likely yield much needed answers regarding the mechanisms involved in
cerebral small vessel disease. Novel insights resulting from this project may also yield promising new targets to
prevent vascular cognitive impairment and dementia in the elderly.

## Key facts

- **NIH application ID:** 10241673
- **Project number:** 3RF1NS110054-01S1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Brian J Bacskai
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,000
- **Award type:** 3
- **Project period:** 2018-09-30 → 2021-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241673

## Citation

> US National Institutes of Health, RePORTER application 10241673, Cerebral microvascular lesions and vascular and neuronal networks (3RF1NS110054-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10241673. Licensed CC0.

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