# Cortical Spreading Depression in the Origins of the Migraine Attack

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $331,406

## Abstract

PROJECT SUMMARY/ABSTRACT
Migraine affects 12% of the world population, and is one of the leading causes of disability worldide. Yet
surprisingly little is known about the basic features of this disease. One of the major questions in migraine is
how its quintessential feature, the migraine attack, is generated. For approximately a third of migraineurs, the
pain of the attack is preceded by an aura, typically a sensory hallucination. Unlike the attack, the aura is
physiologially measurable, in humans and in animal model systems, because its physiological correlate is a
massive depolarization called cortical spreading depression (CSD). By understanding how CSD is generated,
we can understand how the attack begins. Our three aims address the origins of the migraine attack from
different angles. The first aim builds on our work showing that CSD, like the aura, has a predilection for
sensory cortex. We ask why this predilection exists, with the expectation that understanding the mechanisms
will yield insights as to how the aura, and thus the attack, are generated. We use a combination of imaging,
electrophysiology and transporter expression analysis to examine the reuptake of extracellular potassium and
glutamate, with the hypothesis that barrel cortex may exhibit a relative deficiency in reuptake compared to
other regions. The second aim tests the hypothesis that failure or saturation of astrocytic reuptake mechanisms
underlies CSD ignition. Our preliminary data on CSD propagation shows astrocyte activation well in advance of
the wave, and suggests a failure of potassium reuptake at the advancing wavefront. We will genetically ablate
key astrocyte mediators of potassium reuptake as the cortex is brought to CSD threshold in vivo, in order to
test the role of the astrocyte, and determine which mechanism is most important. The third aim asks how CSD,
a massive depolarization, is generated in an ostensibly intact brain. Here our preliminary data on sensory
cortex susceptibility is particularly important, as it allows us to constrain potentially open-ended experiments.
We will systematically test triggers of aura in awake behaving animals while we record from sensory cortex
using two photon microscopy.

## Key facts

- **NIH application ID:** 9939700
- **Project number:** 5R01NS102978-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Kevin Christopher Brennan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $331,406
- **Award type:** 5
- **Project period:** 2017-08-15 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939700

## Citation

> US National Institutes of Health, RePORTER application 9939700, Cortical Spreading Depression in the Origins of the Migraine Attack (5R01NS102978-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9939700. Licensed CC0.

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