Neurocysticercosis (NCC), a parasitic tapeworm infection of the brain, is the major cause of acquired seizures worldwide, but the mediators responsible for seizures in NCC were previously unknown. Prema Robinson and colleagues, realising that Substance P is involved in inflammation, found Substance P in autopsies of the brains of patients who had the tapeworm infection. They did not find Substance P in uninfected brains.
Substance P is a neuropeptide (a small protein-like molecule involved in neuron-to-neuron communication.) It is produced by neurons, endothelial cells (the cells that line blood vessels) and cells involved in host defense. Discovered in the 1930s, it has long been recognised as a pain transmitter. However, in recent years, it has also been found to play a role in many other functions.
Body responds when parasite dies
"As long as the parasite is alive, nothing happens," said Robinson. However, once the worm dies, the body responds with chemicals that recruit immune system cells to the site of infection, causing inflammation. Her studies show that the cells that produce Substance P are found mainly in areas of inflammation near the dead worms.
Animals injected with Substance P alone or with extracts from the areas of inflammation (granulomas) near the worms in infected mice suffered severe seizures, she said. However, when the rodents received the drug that blocks the Substance P receptor, they did not have seizures.
In addition, mice that lacked the Substance P receptor did not have seizures even when injected with the extracts of granulomas from infected mice. Granuloma extracts from mice that lacked the cells that make Substance P did not induce seizures either.
These findings have implications for people, who often suffer seizures during treatment for the tapeworm infection. As the worms die, inflammatory cells rush to the scene and the seizures begin. There are medications known to block the receptor for Substance P. These medications may prove to be the most effective means of treating and preventing seizures in these patients.
(EurekAlert, February 2012)