Brain Damage Newsroom

Is It Just a Headache? Study Links Migraine to Brain Damage in Mice

Migraine headaches are a source of disabling pain for millions of people. Now, a study in mice suggests that these headaches may be linked to tiny areas of stroke-like brain damage. The findings suggest that treatment to prevent migraines may also prevent longer-term cognitive problems. The study, led by Takahiro Takano, Ph.D, and Maiken Nedergaard, M.D., Ph.D., of the University of Rochester Medical Center in New York, focused on a phenomenon called cortical spreading depression (CSD), which occurs in migraines as well as stroke and traumatic brain injury. In CSD, a slow-moving wave of potassium ions causes large numbers of neurons to signal at once, followed by a period when normal neuronal activity in that area is halted.

Drs. Takano and Nedergaard investigated the effects of CSD in the brain using mice. They injected a drug to trigger CSD and watched the effects using a technique called two-photon microscopic imaging. They also used microelectrodes to measure the amount of oxygen in the tissues while the wave of CSD passed through the brain. The study was funded in part by the National Institute of Neurological Disorders and Stroke (NINDS) and appeared in the June 2007 issue of Nature Neuroscience.

The researchers found that CSD caused a short-term drop in oxygen levels and obvious swelling in the neurons. It also caused a temporary loss of dendritic spines, which are tiny projections on neurons that form junctions (synapses) with other neurons. These changes are signs of hypoxia – a state where neurons have too little oxygen to function normally. Hypoxia usually results from reduced blood flow in part of the brain and is what causes brain damage in strokes and transient ischemic attacks (TIAs). In the new study, however, the researchers saw signs of hypoxia even though the amount of blood flow in the brain temporarily increased.

“It is critical for the brain to keep normal levels of potassium,” Dr. Nedergaard explains. It takes a great deal of energy to reduce CSD-related potassium levels in the brain. Producing this energy requires oxygen. Dr. Nedergaard believes the brain’s attempts to reduce excess potassium and halt CSD prompt the temporarily increased blood flow associated with CSD. Unfortunately, however, the study showed that neurons close to the tiny blood vessels in the brain used up most of the increased oxygen. This caused small pockets of hypoxia in brain tissue that was farther away from the blood vessels. The hypoxia lasted for more than two minutes.

“Our study puts forth a new concept: that hypoxia can occur even without reduced blood flow when there is a high energy demand,” Dr. Nedergaard says. The researchers also investigated whether they could decrease the hypoxia associated with CSD by increasing the percentage of oxygen in the air around the mice. They found that 100 percent oxygen shortened the duration of CSD, while decreasing the concentration of oxygen prolonged the duration. Very low oxygen even triggered spontaneous waves of CSD in some mice.