Large and numerous "puffs" of glutamate into the brain could help explain the onset of migraine with aura - and potentially be involved in a wide range of neurological diseases, including strokes and traumatic brain injuries.
This was stated in a study conducted by a team of researchers led by Prof. Daniela Pietrobon of the University of Padua and by prof.
KC
Brennan of the University of Utah.
It is now clear that migraine is a brain disease, but the brain dysfunctions that cause it remain largely mysterious.
The study, conducted in laboratory mice, found that an abnormal increase in glutamate in the extracellular space - the area between brain cells - can trigger tsunami-like depolarization waves that spread through the brain causing migraines and other nervous system disorders. .
"These mice - says Pietrobon - show an increased susceptibility to" cortical spreading depolarization (Csd) ", a wave of depolarization that arises spontaneously in the brain of migraine sufferers and gives rise to the so-called migraine aura. We have shown that in the brains of these mice c 'it is a slowed and ineffective removal of glutamate during brain activity, and that this defect is responsible for the increased susceptibility to Csd ".
Brennan implemented a new technique that allows to optically measure the glutamate that is released during the brain activity of an awake mouse and collaborated with Pietrobon to study glutamate changes during brain activity in migraine model mice in which removal of glutamate at the excitatory synapses is slowed down.
He found that in the cerebral cortex of mutated mice there are occasionally "puffs" of glutamate, that is localized increases in glutamate, which are not present in wild non-mutated mice.
The study then showed that the onset of Csd is preceded by a flurry of these glutamate puffs.
By inhibiting the glutamate puffs, the onset of Csd is also inhibited.
The 'puffs' could therefore play a key role
"We have no direct evidence that these glutamate puffs are present in the human cerebral cortex - observes Pietrobon -. But there are data in migraine patients who show a high level of glutamate in the cerebrospinal fluid compared to healthy controls. Blocking the release of glutamate by inhibiting locally the calcium channels of the neuronal synaptic terminals have blocked the puffs and also the onset of Csd in migraine model mice, but a systemic treatment with these blockers in humans is unthinkable as it would block the physiological synaptic transmission of the brain. It seems the best strategy to go to inhibit specific glutamate receptors or to increase the speed and effectiveness of removing the released glutamate ".
(HANDLE).