Novel way to treat stroke

Jan 9 2006

A joint research effort between researchers at the Burnham Institute for Medical Research in La Jolla, CA, and a team from Japan (Iwate University, Osaka City University, Gifu University, Iwate Medical University) has discovered a novel way to treat stroke and neurodegenerative disorders.

This approach works by inducing nerve cells in the brain and the spine to release natural antioxidants that protect nerve cells from stress and free radicals that lead to neurodegenerative diseases. Until this discovery, researchers were unable to induce release of these specific antioxidants directly in nerve cells, at the site where damage and degeneration occurs.

In stroke and various neurodegenerative disorders, such as Alzheimer's disease and Lou Gehrig's disease, glutamate, an amino acid found in high quantities in the brain, is thought to accumulate. At normal concentrations, glutamate acts as a neurotransmitter that nerves use to communicate. However, at excessive levels glutamate is toxic, resulting in over stimulation of nerve cells, known as excitotoxicity, and causing excessive stress on the nerve cells eventually ending in cell death. Studies described in this report suggest that NEPPs (short for NEurite outgrowth-Promoting Prostaglandins), compounds that accumulate in nerve cells, prevent nerve damage by activating the Keap1/Nrf2 pathway that regulates the production of antioxidants which relieve cells of damaging free radicals that result from excitotoxicity.

"This is the first reported evidence that this protective response can be activated directly in nerve cells to release antioxidants and counter oxidative stress," said Stuart Lipton, M.D., Ph.D., Director of the Del E. Webb Center for Neurosciences and Aging at the Burnham Institute and senior author of the study. "These findings provide support for further investigation of NEPP drugs to potentially treat ischemic stroke, multiple sclerosis, Alzheimer's disease, Lou Gehrig's disease and other neurodegenerative disorders."

Researchers found that NEPPs were able to activate a pathway in nerve cells that is designed to protect against oxidative and nitrosative stress (which produces free radicals) and excitotoxicity. This pathway, known as Keap1/NrF2, regulates the production of natural antioxidants, such as bilirubin, that can protect against oxidative stress resulting from ischemic stroke and degenerative disorders.