# Understanding cellular architecture of the neurovascular unit and its function in the whole mouse brain

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $591,431

## Abstract

ABSTRACT
An intricate web of blood vessels in the mammalian brain provides essential oxygen and nutrients to power the
energy demands of the brain. The structure of the brain’s microvasculature provides the extraordinary surface
needed for a high level of energy exchange and clearance of metabolic wastes. Small vessel pathologies are
involved in cognitive decline associated with aging and many brain disorders. Mounting evidence supports the
idea that neuronal activity dynamically regulates diameter of small vessels to maintain energy homeostasis.
For example, when mice use their whiskers to sense the external environment, neural activity in corresponding
somatosensory areas increases and small vessels in the area dilate to increase blood perfusion. Cortical
interneurons, especially neuronal nitric oxide synthase (nNOS) expressing neurons, are the major cell type to
mediate such neurovascular coupling. Interestingly, emerging evidence suggests that 3D distribution and
function of small vessels, and their interaction with vasomotor neurons are heterogeneous in different brain
regions. Moreover, some brain regions are more susceptible than others to age related degeneration, which
can be linked to many neurological conditions with brain region specific symptoms such as Alzheimer's
disease. To understand the underlying neurovascular mechanisms affected in health and pathological
conditions, we propose to create a precise 3D map of micro vessels and cell types controlling vessel motility in
the entire mammalian brain using the mouse as a model. Furthermore, we aim to gain a comprehensive
understanding of neurovascular changes during aging. Towards this goal, we have created a synergistic
collaborative team with complementary skill sets to establish high-resolution whole mouse brain anatomical
maps of micro vessels and nNOS interneurons subtypes (Dr. Kim), to establish a web-visualization to widely
disseminate these maps (Dr. Cheng), and to study functional relationships involved in the regulation of
vasomotility from awake animals (Dr. Drew). The proposed work will establish reference maps that are needed
as a foundation for the further study of neurovascular architectures supporting normal cognitive function and
their changes in various neuropathologies.

## Key facts

- **NIH application ID:** 9919633
- **Project number:** 5R01NS108407-03
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Yongsoo Kim
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $591,431
- **Award type:** 5
- **Project period:** 2018-09-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9919633

## Citation

> US National Institutes of Health, RePORTER application 9919633, Understanding cellular architecture of the neurovascular unit and its function in the whole mouse brain (5R01NS108407-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9919633. Licensed CC0.

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