# Resilient versus fragile aspects of blood flow in the mammalian brain

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $813,686

## Abstract

Principal Investigator (Last, first, middle): KLEINFELD, DAVID
 We propose to advance our understanding of the key factors involved in the distribution of blood within the
brain. Our focus begins with the relation of flow dynamics to the topology of the underlying angioachitecture. In
cortex, a highly interconnected network of surface vessels and a network of subsurface vasculature were
shown to be effective in distributing blood and in providing a robust immunity to occlusions. In contrast, the
penetrating arterioles that shuttle blood from the cortical surface to the underlying microvessels were shown to
be a bottleneck to the supply of blood within the brain and a locus for cognitive decline after a microstroke. We
will determine if other brain areas follow the same vascular plan or rather have a different set of design rules.
Our initial emphasis is on hippocampus, given the great sensitivity of hippocampal neurons to ischemia.
 While the topology of the vasculature is fixed, the diameter and thus the resistance to flow of individual can
change. First, the diameter of brain blood vessels changes with vasomotion at a frequency of 0.1 Hz. It is not
known if this slow signal phase-locks to vasomotion in a distant region or in the contralateral hemisphere that is
also activated by a common stimulus. We will determine the effects of awake sensory stimulation on
vasomotion along pathways over large regions of cortex. The finding of activity induced correlation of
vasomotion should have implications as a basis for the functional connectivity derived by bold oxygenation
level dependent (BOLD) functional magnetic resonant imaging (fMRI). A second aspect of neurovascular
signaling concerns changes in diameter in arterioles and potentially microvascular capillaries in response to
modulators released by stimulus-induced neural activity. The mechanism by which neural activity leads to both
vasoconstriction and to vasodilation is a puzzle. We will determine the competitive nature of vasoactive
signaling by concomitant measure of extrasynaptic modulator concentration and activation of specific neuronal
subtypes in terms of their affects on changing blood flow through vasoconstriction or vasodilation.
 We note that all of the proposed experiments make use of a broad range of technologies, ranging from
behavior to physiology to probes to imaging, and thus provide a fertile test bed for scientific discovery as well
as a means to train the next generation of neuroscientists as generalists.

## Key facts

- **NIH application ID:** 9830083
- **Project number:** 5R35NS097265-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Kleinfeld
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $813,686
- **Award type:** 5
- **Project period:** 2016-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9830083

## Citation

> US National Institutes of Health, RePORTER application 9830083, Resilient versus fragile aspects of blood flow in the mammalian brain (5R35NS097265-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9830083. Licensed CC0.

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