In Murine Model, Migraine Causes TIA-Like Brain Damage

ROCHESTER, N.Y., May 2 -- An induced mouse migraine, or migraine-like event, may cause brain damage as well as a bad murine headache, suggest researchers here.

In a mouse, an induced migraine may trigger the equivalent of a human transient ischemic attack, Takahiro Takano, Ph.D., of the University of Rochester, and colleagues, reported online in Nature Neuroscience.

"We're saying that migraines may be causing brain damage, and that the focus should be on prevention, which will stop not only the pain but also minimize potential damage," the authors said in a statement.

Migraines -- despite their skull-splitting, incapacitating pain -- are usually thought to be relatively benign, Dr. Takano added. Yet "in mice, the damage from these episodes looks exactly like the damage that occurs to the brain from repeated TIAs."

Novel imaging techniques, used to view a phenomenon called cortical spreading depression in the brains of mice, also revealed tiny areas of tissue that were starved of oxygen.

Cortical spreading depression is wave of cellular depolarization that has been linked both to migraines and to neuronal injury after stroke and head trauma, Dr. Takano and colleagues said.

Clinicians have known for a long time that a migraine can leave its victim functionally impaired from the pain, they added. And recently researchers have shown that repeated migraines worsen a person's cognitive abilities.

"But actually doing damage to the brain -- that is a surprise," Dr. Takano said.

The clinical implication of the study is that simply treating the pain is not enough, according to co-author Maiken Nedergaard, M.D., Ph.D., also of Rochester.

Using a technique called two-photon imaging, the researchers were able to see what happens to the brains of living mice as a wave of cortical spreading depression passes through.

Surprisingly, blood flow to the brain actually increased during the cortical spreading depression event, they found. The brain's arteries expanded by 50% to bring more oxygen to the tissues.

But while tissue close to blood vessels was getting oxygen, tiny areas further away were starved and hypoxic. In these areas, neurons swelled and began to disintegrate, shedding up to 75% of the dendritic spines that make up the synapses.

In contrast, astrocytes were not affected, they found.

The damage to the neurons was comparable to what happens when blood flow to the brain is completely cut off, as in cardiac arrest, Dr. Takano and colleagues said.

The clinical manifestation of the hypoxia, Dr. Takano and colleagues suggested, might be the aura, which includes visual defects or black spots, that is part of many migraines.

"If so, the severity of metabolic stress associated with migraine aura is comparable to that associated with transient ischemic attacks," they said. "And the striking distortion of dendritic structures may be linked to long-term changes of synapses and cortical networks in those suffering from repeated migraine attacks."

Some studies have shown that patients who get auras with their migraines are at increased risk for vascular problems such as a heart attack or stroke, according to Deborah Friedman, M.D., also of the University of Rochester, but not involved in the study.

Dr. Friedman, a member of the board of directors of the American Headache Society, called for more effort to prevent migraines.

"It's astounding just how many migraine sufferers do not see a doctor and are not on a medication to prevent a recurrence," Dr. Friedman said in a statement. "Doctors and patients need to be diligent and rigorous about using preventive medications for migraine."