Researchers at the University of Iowa and the Veterans Affairs Iowa City Health Care System have uncovered a brain pathway that shuts down seizures.
The multidisciplinary team of scientists pieced together information from clinical observations made in the first half of the 20th century with knowledge from modern genetics and molecular biology to show that an acid-activated ion channel in the brain reacts to a drop in pH (increased acid) in a way that shuts down seizure activity.
The link between low pH in the brain and seizure termination was first hinted at nearly 80 years ago when clinical experiments showed that breathing carbon dioxide, which makes brain tissue more acidic, helps stop epileptic seizures. Subsequent studies in the 1950s found that seizures themselves reduce brain pH. However, it was the modern discovery of an acid-activated ion channel (ASIC1a) in the brain that provided the key to the UI discovery, which is reported in Nature Neuroscience Advance Online Publication on June 8.
"We found that ASIC1a does not seem to play a role in how a seizure starts, but as the seizure continues and the pH is reduced, ASIC1a appears to play a role in stopping additional seizure activity," said Adam Ziemann, a student in the Medical Scientist Training Program at the UI and co-lead author of the study.
Specifically, the study shows that mice without the ASIC1a gene have more severe and longer seizures than mice with the gene. In addition, chemically blocking ASIC1a increases the severity and duration of seizures in mice with the gene. Conversely, increasing the expression of ASIC1a in mice protects the animals from severe seizures.
The team also showed that reducing the pH in slices of brain tissue expressing ASIC1a reduced seizure activity, but acid had no effect on seizures in tissue without the protein.
When the team measured pH in mouse brains, they showed that seizures lower the pH to levels that c
|Contact: Jennifer Brown|
University of Iowa