# Brain Vascular Heterogeneity

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $287,823

## Abstract

Project Summary
 In a variety of neurological conditions brain abnormalities have been observed in specific
brain areas using MRI and immunohistological methods. These include patients suffering from
stroke, small vessel disease, multiple sclerosis and infectious diseases, such as cerebral
malaria (CM). Many neurological conditions contain an underlying vascular component.
Brain vascular pathologies appear to differ according to vessel size and specific brain area the
vessels reside in, including differences in vessels residing in gray matter (GM) versus white
matter (WM). These differing pathologies are especially clear in CM: hemorrhagic punctae in
WM but not in GM. Little is known of exactly what these differences are, the underlying causes
of these vascular differences in GM versus WM and how these differences could relate to
divergent neuropathological responses.
 We hypothesize that, cerebral microvessels derived from various GM and WM brain
regions, exhibit differing properties, including different expression of transporters, receptors,
junctional molecules and cell adhesion molecules. These differences are due to differences in
the metabolic and functional needs of the direct physiological environment of these cerebral
microvessel, including presence of astrocyte-neuronal versus pericyte-oligodendrocytes. These
differences may be responsible for the varying inflammatory- and hemorrhagic- responses to
stimuli, such as microbial stimulation, oxygen deprivation in stroke, or responses to
therapeutics.
 In this proposal we intend to study the underlying differences of the brain’s vasculature
using a comprehensive approach using human brain samples of different brain areas in
combination with in-vitro BBB modeling. We propose to compare A) the global expression
differences of the brain micro-vasculature. Thereafter, distinctive vascular markers that are
specific for certain brain areas will be selected and their expression confirmed in different brain
areas. B) Functional responses of brain endothelium will be tested using in vitro BBB models that
have properties reflecting these vascular differences, e.g. WM and GM brain endothelium.
 We anticipate that this proposal will lead to clarification of vascular differences in the
different brain areas and will offer an explanation for differing pathologies observed in
neurological conditions. A better understanding of the vascular heterogeneity may lead to future
development of novel targeted therapeutics.

## Key facts

- **NIH application ID:** 10128613
- **Project number:** 1R21NS114461-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** CARLOS A PARDO-VILLAMIZAR
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $287,823
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10128613

## Citation

> US National Institutes of Health, RePORTER application 10128613, Brain Vascular Heterogeneity (1R21NS114461-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10128613. Licensed CC0.

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