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By Shutting Down Inflammation, Agent Reverses Damage From Spinal Cord Injury In Preclinical Studies

Date:
April 1, 2009
Source:
Georgetown University Medical Center
Summary:
Researchers have been able to speed recovery and substantially reduce damage resulting from spinal cord injury in preclinical studies.
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Researchers at Georgetown University Medical Center (GUMC) have been able to speed recovery and substantially reduce damage resulting from spinal cord injury in preclinical studies.

Their research, published online in Annals of Neurology and led by Kimberly Byrnes, PhD, shows that inflammation following injury causes the neurotoxicity that leads to lasting nerve cell damage, and that an experimental agent is able to block this inflammatory reaction.

“The findings we have made in this study may potentially be applicable to other neurological disorders, including stroke, head injury, Alzheimer’s disease and Parkinson’s disease,” says senior investigator Alan I. Faden, MD, a professor of neuroscience and director of the Laboratory for the Study of Central Nervous System Injury at GUMC.

Faden says that the experimental agent they tested (CHPG), an activator of a type of glutamate receptor, is not ideal for human use because it cannot easily penetrate the blood-brain barrier. But he adds, “now that we know the biological target, a new drug could be designed that is better suited for clinical treatment of these neurodegenerative disorders.”

CHPG shuts down activation of key immune cells in the brain known as microglia, which sense pathogens or damage in the spinal cord and brain. They helpfully foster the destruction of microbial invaders and clean up biological detritus that occurs after an injury, but researchers say they have a dark side as well – they can worsen the damage by releasing toxic inflammatory factors.

“Under certain conditions, like spinal cord injury and brain trauma, microglia become activated,” Faden says. “They release toxic chemicals that can kill healthy adjacent tissue, and this process can continue for months.

“We have found that six months after an injury, the expression of certain inflammatory factors in the spinal cord is 4-5 times normal levels,” he says, adding that it has been shown that after human trauma, brain tissue can continue to be lost even more than a year after the injury. “Microglial related toxicity may contribute to this progressive loss,” says Faden.

The study is a continuation of a long line of research by this investigative group that aims to stop that persistent damage. The team had previously found that microglial cells express a certain receptor, the group I metabotropic glutamate receptor 5 (mGluR5), on their surface. Further work showed that if these receptors were specifically activated on microglia, these immune cells would not produce the neurotoxins that led to cell death near the site of injury. CHPG serves to selectively activate the receptor, reducing microglial toxicity.

The study was funded by grants from the National Institute of Neurological Diseases and Stroke. Faden and Byrnes are co-inventors on a patent application that has been filed by Georgetown University related to the technology that is described in this paper. The other co-authors are Bogdan Stoica, MD, Angela Riccio, BS, Ahdeah Pajoohesh-Ganjai, PhD, and David J. Loane, PhD, all from the Department of Neuroscience at GUMC.


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Materials provided by Georgetown University Medical Center. Note: Content may be edited for style and length.


Cite This Page:

Georgetown University Medical Center. "By Shutting Down Inflammation, Agent Reverses Damage From Spinal Cord Injury In Preclinical Studies." ScienceDaily. ScienceDaily, 1 April 2009. <www.sciencedaily.com/releases/2009/03/090331112721.htm>.
Georgetown University Medical Center. (2009, April 1). By Shutting Down Inflammation, Agent Reverses Damage From Spinal Cord Injury In Preclinical Studies. ScienceDaily. Retrieved March 28, 2024 from www.sciencedaily.com/releases/2009/03/090331112721.htm
Georgetown University Medical Center. "By Shutting Down Inflammation, Agent Reverses Damage From Spinal Cord Injury In Preclinical Studies." ScienceDaily. www.sciencedaily.com/releases/2009/03/090331112721.htm (accessed March 28, 2024).

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