The brain depends on a constant supply of oxygen. This is why a
stroke can have fatal consequences. Whether caused by cerebral
hemorrhage or a blocked artery, the oxygen deficit triggers a rapid loss
of nerve cells.
Stroke is, therefore, one of the most common causes of
death, and even if the patient survives, paralysis, speech difficulties
or other disabilities may remain depending on which part of the brain
‘A signaling pathway that acts upon the calcium concentration in astrocytes may be a potential starting point for treating stroke in humans.’
The damaged area can even expand to some extent. This is due to
"spreading depolarizations", which can occur minutes after a stroke and
may recur over the following days. They start at the infarct core and
engulf the surrounding tissue like an avalanche. These electrical
discharges put the cells under severe stress.
Researchers at the German Center for Neurodegenerative
Diseases (DZNE) have investigated the mechanisms of these "spreading
depolarizations" in mice, and found that brain cells termed astrocytes
potentiate the fatal discharges.
The study highlights potential
counter-measures: a signaling pathway that acts upon the calcium
concentration in astrocytes may be a potential starting point for
treating stroke in humans. Dr. Cordula Rakers and Prof. Gabor Petzold
report on these findings in "The Journal of Clinical Investigation
depolarizations radiate into the healthy tissue. Each wave can increase
the volume of the brain affected by stroke," says Petzold.
"Incidentally, these depolarizations do not occur only in stroke but
also in other severe brain injuries. A therapy might therefore be
relevant for many neurological diseases."
Favorable opportunities for treatment might arise from the fact
that the discharges spread over several days. Petzold notes, "Each wave
is potentially harmful. However, the damage occurs gradually as there is
a cumulative effect. Treatment could therefore have a positive impact,
even if it is given days after the stroke. The time window for treating
spreading depolarizations might therefore be larger than in established
therapies against stroke."
Harmful interaction between nerve cells and astrocytes
DZNE researchers have now discovered how various events and cell
types interact during spreading depolarizations, thereby intensifying
the discharge. Cells known as astrocytes play a key role. These cells
form a dense network with the brain's nerve cells and are involved in
various metabolic processes.
"When nerve cells depolarize, they release large quantities of the
neurotransmitter glutamate. Glutamate then diffuses to other cells, in
particular to neighboring astrocytes," explains Petzold. "This was known
before. However, we have now been able to show what follows this event.
The glutamate causes calcium levels in the astrocytes to soar. As a
result, the astrocytes release glutamate as well. This in turn can act
on nerve cells. A vicious circle emerges that potentiates the spreading
depolarizations. This process is amplified by the astrocytes."
The neuroscientists were also able to show that certain drugs can
interrupt this chain of events. Ultimately, these drugs reduce the
abnormally elevated calcium levels in astrocytes. "At present, there is
no established treatment that directly affects spreading
depolarizations. Our results show that it is possible to reduce the
frequency and severity of these discharges by modulating the astrocytes'
calcium metabolism. In theory, this could also be possible in humans.
This could lead to a new approach to treating stroke," says Petzold.