An Anti-Inflammatory Agent Could Reverse Spinal Cord Injury Damage

Researchers at Georgetown University Medical Center (GUMC; Washington, DC, USA; gumc.georgetown.edu) tested the glutamate receptor activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG) so as to selectively activate the group I metabotropic glutamate receptor 5 (mGluR5) found on the surface of microglial cells. Laboratory rats received intrathecal infusion of CHPG for 7 days after moderate impact spinal cord injury (SCI) at T9. Complementary studies examined CHPG effects on activated spinal microglia cultures. The researchers found that functional motor recovery was significantly increased by CHPG treatment up to 28 days after injury, with improvements in weight bearing, step taking, and coordination of stepping behavior. CHPG treatment also significantly reduced lesion volume and increased white matter sparing at 28 days post-injury. The mGluR5 stimulation also reduced microglial activation and decreased microglial-induced neurotoxicity in spinal cord cell cultures, as the immune cells shut down production of the neurotoxins that lead to cell death near the site of injury. The study was published early online on March 26, 2009, in the Annals of Neurology.

"Under certain conditions, like spinal cord injury and brain trauma, microglia become activated," said senior investigator Alan Faden, M.D., Ph.D. "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; it has been shown that after human trauma, brain tissue can continue to be lost even more than a year after the injury."

"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," added Dr. Faden, a professor of neuroscience and director of the laboratory for the study of central nervous system injury at GUMC.

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