# Hemorheological Factors in Cerebral Ischemia

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2021 · $608,107

## Abstract

Project Summary/Abstract
 This project (begun in 1984) continues its long-term goal to enhance understanding of stroke by novel
mechanistic investigations. Our principal interest is cerebral microhemorrhage, the pathological substrate of
cerebral microbleeds and the major hemorrhagic component of microvascular cerebral disease. The proposed
project will utilize a combination of novel animal models of cerebral microbleeds, new cell culture models of
microbleeds that address red blood cell (RBC)-endothelial interactions, and cutting edge analytic techniques.
Our objective is to identify mechanisms that broadly impact development of cerebral microbleeds as well as
those more specifically related to individual vascular risk factors for microbleeds, The project investigators are
a unique group of investigators with expertise in stroke neurology, vascular neurobiology, nephrology,
bioengineering, and biostatistics, all with capabilities relevant to animal and cell culture studies.
 We specifically propose the following aims:
Specific Aim 1: To determine mechanisms of cerebral microhemorrhage in vivo.
Specific Aim 2: To delineate paracellular mechanisms of RBC passage across brain microvascular
endothelium in vitro.
Specific Aim 3: To delineate transcellular mechanisms of RBC passage across brain microvascular
endothelium.
 The proposed studies are designed as a series of synergistic experiments that combine in vivo and in
vitro studies to provide novel insights into microvascular brain disease. We will use a combination of studies of
microvascular physiology and neuropathology to identify the vascular source of cerebral microbleeds and to
delineate those interactions between RBC and brain microvascular endothelium that immediately precede
establishment of cerebral microbleeds. The project is a direct extension of work we completed during the most
recent funding period of this grant and incorporate new animal models of cerebral microbleeds and novel
conceptual models describing microbleed pathogenesis. Our in vivo studies will address mechanisms of
aging, hypertension, and chronic kidney disease in microbleed development, along with the roles of microglia
and matrix metalloproteinase-9.
 This project directly addresses the highly prevalent problem of hemorrhagic microvascular disease of
the brain. Our work and that of others have shown the near-ubiquitous presence of microhemorrhagic
changes in aging human brain. Our multi-disciplinary team of investigators are uniquely capable of taking this
project to completion, directly testing our microbleed conceptual models in the expectation that robust insights
will emerge helping to transform the management of microvascular disorders of the brain which, along with
Alzheimer’s disease, represents the most common cause of neurological morbidity of aging.

## Key facts

- **NIH application ID:** 10145800
- **Project number:** 5R01NS020989-33
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** David Hastings Cribbs
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $608,107
- **Award type:** 5
- **Project period:** 1984-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145800

## Citation

> US National Institutes of Health, RePORTER application 10145800, Hemorheological Factors in Cerebral Ischemia (5R01NS020989-33). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10145800. Licensed CC0.

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