A migraine is an episodic, intense and debilitating headache characterized by severe pain on one or both sides of the head, which is often accompanied by nausea or vomiting.The condition is very common, affecting 1 in 4 women and 1 in 12 men (that is, between 12-28% of the population), but its cause remains unknown. One theory is that migraines are caused by rapid constriction and dilation of the blood vessels in the brain. Another hypothesis is that migraine is caused by cortical spreading depression (CSD), a wave of nerve cell inhibition that propagates itself across neural tissue; CSD has also been implicated in stroke and other types of brain trauma.
A new study by researchers form the Department of Neurosurgery at the University of Rochester Medical Center in New York, published online in Nature Neuroscience, shows that the damage to neural tissue that occurs during a migraine episode is exactly the same as the damage that occurs in a transient ischaemic attack, a minor stroke in which blood flow to parts of the brain is temporarily interrupted. The study povides evidence that migraines act like transient mini-strokes – they starve parts of the brain of oxygen, leading eventually to damage of those parts.
Maiken Nedergaard and her colleagues induced CSD in mice, and used a combination of state-of-the-art imaging techniques to observe, at cellular resolution, the metabolic and structural changes that occur in neurons during the migraines. They found that CSD is associated with depleted levels of oxygen (hypoxia) in brain tissue. This hypoxia can occur even though there is no decrease in blood supply. This seemingly paradoxical situation arises because, during CSD, the consumption of oxygen exceeds the rate at which the gas can be supplied. It appears that the cells closest to capillaries consume the available oxygen, at the expense of cells further away.
It was also found that the wave of CSD caused a change in the structure of neurons in the affected areas of the brain. Strains of transgenic mice expressing yellow or green fluorescent protein were created, and two-photon fluorescence microscopy was then used to image the intact exposed brains of live the animals.
Looking at neurons in layer 2 of the cerebral cortex, the researchers found that, as the CSD wave front passed over the cells, neuronal cell bodies increased in volume, and the cells lost many of their dendritic spines. Cell bodies increased by almost 40%, but returned to their pre-CSD volume within 10 minutes. (Watch a film clip of this process here.) The breakdown in the structure of the dendritic trees occurred within seconds of the wave reaching the cells, but was also temporary. In some cases, it was very severe – 4 out of 10 mice lost an average of almost 80% of dendritic spines in cortical layer 2 cells.
In about 25% of migraine sufferers, the headache is preceded by visual disturbances called the aura. Nedergaard suggests that the aura could be a warning that some parts of the brain are being starved of oxygen. Treatment of migraine has usually focused to alleviating pain – sufferers often take non-steroidal anti-inflammatories such as aspirin or paracetomol – and it is estimated that less than 20% of migraine sufferers who need preventative treatment actually receive it. The new findings suggest that those who suffer from migraines should try to prevent their headaches altogether, to minimize the possibility of brain damage. In some people, migraines can be brought on by various triggers, such as bright lights or loud noises, physical or emotional stress, and various drugs, including alcohol and caffiene. Migraines could be prevented by avoiding those triggers – at least in people who know what those triggers are.
Takano, T., et al. (2007). Cortical spreading depression causes and coincides with tissue hypoxia. Nat. Neurosci. doi: 10.1038/nn1902. [Abstract]