# Whole Genome RNA Sequencing (RNAseq) of Blood from Patients with Lacunar Stroke

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $564,925

## Abstract

Abstract
 Lacunar strokes are small infarctions of deep penetrator end arteries that supply deep areas of brain
including the basal ganglia, internal capsule, thalamus and pons. The “cause” of lacunar strokes has been
controversial. C Miller Fisher was the first to suggest that hypertension was one cause, noting lipohyalinosis
(inflammation, fibrinoid necrosis of vessel wall) in smaller penetrating arteries (<200um) occurred only in
hypertensives. He also showed, however, that larger lacunar strokes were often associated with
microatheroma associated narrowing of larger penetrating arteries. This pathology is now thought to be the
most common and associated with lipid abnormalities and diabetes. Moreover, some lacunar strokes are now
thought to be associated with intracranial atherosclerosis of the parent artery at the origin of the penetrators.
Though lacunar strokes were not traditionally associated with large vessel extracranial atherosclerosis or
cardioembolism, there are now a number of cases where lacunar strokes have been associated with large
vessel atherosclerosis or cardiac causes. Indeed, in our own recent study we showed that as many as ~50% of
small deep infarcts (>15mm in size) were predicted to be due to large vessel atherosclerosis or to
cardioembolic disease. It is crucial to identify the correct causes of lacunar strokes because treatments differ:
drugs for hypertension vs drugs for lipid abnormalities, surgery for large vessel carotid disease, anticoagulants
for cardioembolic disease, and anti-platelet agents for lacunar strokes associated with hypertension or
abnormal lipids or diabetes. The biology of lacunar strokes has been studied very little, and there are no
accepted biomarkers for lacunar stroke or its causes. Our group, however, has begun to provide novel insights
into how the immune and clotting profiles in peripheral blood differ in lacunar strokes compared to large vessel
and cardioembolic strokes. We have shown that the immune response in large vessel and cardioembolic
cortical strokes is mainly associated with neutrophil genes, whereas the immune response in lacunar stroke
associated with hypertension /lipids/ diabetes is associated with inflammatory monocyte-related genes.
However, since the preliminary studies were performed on whole blood, there is a great need to study
individual immune cell types in these different causes of ischemic stroke. Therefore, in this study we will isolate
neutrophils and monocytes in patients with lacunar stroke compared to large vessel and cardioembolic stroke.
We will perform RNA sequencing on those cells in the following aims which allows us to measure expression
levels of >250,000 alternatively spliced transcripts which are derived from the ~20,000 coding genes.
 Specific Aim #1. Use RNAseq to demonstrate that alternatively spliced transcript level expression
profiles in monocytes, neutrophils and whole blood differ for subcortical lacunar strokes associated with
hypertension, a...

## Key facts

- **NIH application ID:** 10168660
- **Project number:** 5R01NS101718-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** FRANK R SHARP
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $564,925
- **Award type:** 5
- **Project period:** 2017-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168660

## Citation

> US National Institutes of Health, RePORTER application 10168660, Whole Genome RNA Sequencing (RNAseq) of Blood from Patients with Lacunar Stroke (5R01NS101718-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10168660. Licensed CC0.

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