Are Migraines A Neuroprotective Response to Oxidative Stress?

A new theory about migraine attacks being proposed is that they are an integrated mechanism by which the brain protects and repairs itself.

Previous research suggests that people who experience migraines have higher levels of oxidative stress. Jonathan Borkum, PhD, of the University of Maine, notes that migraine triggers — including stress, sleep disruption, noise, air pollution, and diet — can increase brain oxidative stress, an imbalance between the production of free radicals and the ability of the body to counteract their harmful effects.

“Oxidative stress is a useful signal of impending harm because a number of unfavorable conditions in the brain can give rise to it,”

said Dr. Borkum. Targeting oxidative stress might help prevent or preempt migraines.

Feedback Loops

Migraines affect approximately 14 percent of the world’s population, or 1.04 billion people. In the United States alone, migraine causes an estimated $36 billion annually in lost productivity, including 113 million lost work days.

In his article, Dr. Borkum looks at the components of a migraine attack individually. In the context of a known threat to the brain — an interruption in blood supply — each of the components is protective. These include strengthening antioxidant defences, lowering the production of oxidants, lowering energy requirements and, especially, releasing growth factors, through blood platelet activation and aggregation into the brain, which protect existing neurons and support the birth and development of new neurons.

Brain derived neurorophic factor (BDNF), calcitonin gene-related
peptide (CGRP), vascular endothelial growth factor (VEGF), and serotonin release have all been found to be stimulated in migraine.

“There are feedback loops between these components of a migraine attack that tie them together into an integrated system,” Dr. Borkum explained. “Thus, it seems likely that migraine attacks are not simply triggered by oxidative stress, they actively protect and repair the brain from it.”

Reducing Oxidative Stress

For years, the temptation has been to see a migraine attack — the pain, nausea, and sensitivity to light and sound — as the disorder. Usually, though, the symptoms of a disease, for example, fever, swelling, pain, or cough, are not the disease itself but rather part of the body’s defence against it.

“So, the theory here tells us that to truly solve migraines we must look beneath the attack to understand the brain’s underlying vulnerability, that is, what gives rise to the oxidative stress,” said Dr. Borkum.

The theory suggests new directions for finding preventive medications and lifestyles, ones that focus on reducing oxidative stress and increasing the release of growth factors. It also sheds light on neural housekeeping, or how the brain maintains and heals itself.

“The existence of an integrated system for protecting and repairing the brain could turn out to be quite useful—for example, we might one day be able to learn from this mechanism how to prevent neurodegenerative diseases,”

said Dr. Borkum.

Jonathan M. Borkum
The Migraine Attack as a Homeostatic, Neuroprotective Response to Brain Oxidative Stress: Preliminary Evidence for a Theory
Headache: The Journal of Head and Face Pain (2017). DOI: 10.1111/head.13214

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