Frontier: Receptors, growth factor may keep astrocytes in line

by Tom Valeo

January, 2009

Astrocytes nourish, protect and repair neurons, but after a traumatic brain injury or a stroke these humble servants turn into saboteurs, unleashing a toxic cascade that compounds the original damage. Researchers presented two possible ways of preventing this cascade.

Experiments by David Meaney, a professor of bioengineering at the University of Pennsylvania, suggest that the damage results from waves of calcium that astrocytes release in order to communicate with one another.

Normally these waves prod astrocytes to release glutamate, the most abundant excitatory neurotransmitter in the brain. Using two-photon imaging to monitor brain activity in a mouse as it received mild blows to the exposed cortex, Meaney determined that the trauma caused ATP, a molecule vital to energy metabolism within cells, to disrupt purinergic receptors on the astrocytes.

These receptors lost their ability to control the release of calcium, which quickly reached toxic levels. “We found that purinergic receptors are key in controlling this chemical activation,” Meaney said. “These receptors could be a new therapeutic target.”

One way to prevent the toxic cascade from causing dangerous swelling of the brain could be to administer erythropoietin (EPO), a major blood cell growth factor, according to Eli Gunnarson of the Karolinska Institute in Stockholm.

The excess glutamate released in the brain after injury from trauma, stroke or disease disrupts the water channel aquaporin-4 on astrocytes, allowing toxic amounts of water to flood them, Gunnarson said.

She and her colleagues demonstrated that administering EPO to mice prevented excess water uptake by astrocytes.

“The animals that received treatment with EPO were found to have significantly fewer neurological symptoms than animals that received only a salt solution,” Gunnarson said. “Our results suggest a potential new way to treat brain injuries that are accompanied by brain edema (swelling) or other disturbances in brain water balance.”