Article ID Journal Published Year Pages File Type
4329115 Brain Research 2008 12 Pages PDF
Abstract
Elevation of extracellular glutamate contributes to cell death and functional impairments generated by spinal cord injury (SCI), in part through the activation of the neurotoxic cytokine interleukin-1β (IL-1β). This study examines the participation of IL-1β and its regulation by the endogenous interleukin-1 receptor antagonist (IL-1ra) in glutamate toxicity following SCI. Glutamate, glutamatergic agonists and SCI had similar effects on levels of IL-1β and IL-1ra. Following spinal cord contusion or exposure to elevated glutamate, concentrations of IL-1β first increased as IL-1ra decreased, and both then changed in the opposite directions. Applying the glutamate agonists NMDA and S-AMPA to the spinal cord caused changes in IL-1β and IL-1ra levels very similar to those produced by contusion and glutamate. The glutamate antagonists MK801 and NBQX blocked the glutamate-induced changes in IL-1β and IL-1ra levels. Administering IL-1β elevated IL-1ra, and administering IL-1ra depressed IL-1β levels. Infusing IL-β into the spinal cord impaired locomotion, and infusing IL-1ra improved recovery from glutamate-induced motor impairments. We hypothesize that elevating IL-1ra opposes the damage caused by IL-1β in SCI by reducing IL-1β levels as well as by blocking binding of IL-1β to its receptor. Our results demonstrate that IL-1β contributes to glutamate damage following SCI; blocking IL-1β may usefully counteract glutamate toxicity.
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