# Glial regulation of neurovascular coupling in CNS disorders

> **NIH NIH R01** · OREGON HEALTH & SCIENCE UNIVERSITY · 2020 · $336,875

## Abstract

PROJECT SUMMARY
Increased neuronal activity in the central nervous system (CNS) elicits corresponding increases in local
cerebral blood flow. This response, termed neurovascular coupling, is lost or attenuated in several CNS
disorders, including stroke, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), multiple sclerosis
(MS), and traumatic brain injury (TBI). The resulting decrease in blood glucose and oxygen available to actively
firing and recovering neurons is likely to exacerbate neuronal damage and contribute to neurological
deterioration. Therefore, a key goal of therapeutic management in these conditions includes restoration of
blood flow. However, the mechanisms underlying the attenuation of neurovascular coupling in disease are
unknown, complicating the development of effective therapeutics for use in the clinic. We have previously
demonstrated that astrocytes are necessary intermediates that convey signals from metabolically active
neurons to microvascular capillaries but not arterioles. Of relevance to this proposal, astrocytes are also
exquisitely sensitive to changes in their environment and become reactive in response to CNS insults. This
response encompasses drastic changes in astrocyte morphology and gene expression patterns, but the
consequence of these changes on neurovascular coupling remain undefined. We hypothesize that aberrant
signals from reactive astrocytes are responsible for the attenuation of neurovascular coupling in injury or
disease. Our preliminary data support this hypothesis: after an experimental model of stroke wherein astrocyte
reactivity is induced, activity-dependent dilation is significantly attenuated at capillaries, the vascular
compartment regulated by astrocytes. Therefore, our goal is to determine the mechanism(s) by which reactive
astrocytes might suppress capillary dilation. Specifically, we will test the hypothesis that neurovascular
coupling is suppressed selectively at capillaries but not arterioles following stroke (Aim 1), determine whether
activity-evoked responses of reactive astrocytes are selectively altered in astrocyte endfeet terminating on
capillaries but not on arterioles (Aim 2), and identify the signaling pathways responsible for the suppression of
activity-evoked capillary dilation (Aim 3).

## Key facts

- **NIH application ID:** 9902567
- **Project number:** 5R01NS110690-02
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Anusha Mishra
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $336,875
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9902567

## Citation

> US National Institutes of Health, RePORTER application 9902567, Glial regulation of neurovascular coupling in CNS disorders (5R01NS110690-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9902567. Licensed CC0.

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