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Protecting nerve cells after injury.

In some cases, an injury to the head or spine causes damage to nerve cells in phases. First comes the initial injury. Then secondary effects set in: inflammation, tissue breakdown, and a host of other physical reactions to injury.

While medical treatment often can do little to mitigate the effect of initial trauma to nerve cells, many researchers believe that speedy intervention can prevent further degradation of nerves and tissues near the injured site.

John M. McCall, a chemist at the Upjohn Co. in Kalamazoo, Mich., described the ongoing study of a class of compounds that do appear to reduce the secondary phases of nerve damage after injury to the brain or spinal cord, including stroke or hemorrhage, has occurred.

The class of compounds bears the name Lazaroids, also known as 21-aminosteroids. One of those compounds, tirilazad mesylate, is now in the final phase of trials with 1,700 patients. So far, the drug has proved safe and effective for treating certain types of acute head and spinal cord injuries, McCall reports.

In one study of 1,015 patients, researchers saw mortality drop by 43 percent overall among persons with subarachnoid hemorrhages -- a specific brain injury due to a ruptured blood vessel. Patients also showed less nerve damage once their bleeding had stopped and improved recoveries, McCall says.

The drug functions as an antioxidant, binding to the lipid bilayer of a cell membrane and serving as a protective agent. Once neurons have experienced trauma, they can suffer an onslaught of oxygen radicals that cause a degenerative condition called cell membrane lipid peroxidation.

"If unchecked, lipid peroxidation spreads over a cell membrane's surface, severely disrupting its function," says McCall.

"This is where tirilazad comes in. It blocks lipid peroxidation. On a larger level, it also blocks some inflammatory reactions that lead to further injury. This is part of its neuroprotective effect."
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Title Annotation:tirilazad mesylate prevents secondary phases of nerve damage injury to brain or spinal cord by blocking some inflammatory reactions
Author:Lipkin, Richard
Publication:Science News
Article Type:Brief Article
Date:Sep 3, 1994
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