Traumatic brain injury (TBI) induces a state of microglialactivation, which includes upregulation of macrophage functions and release inflammatory mediators such as certain inflammatory cytokines. Current literature suggests that interleukin-1Beta is an important cytokine mediator, which is dramatically increased after brain injury. Previous studies indicate that ATP is released by traumatically injured astrocytes and serves as a cell-to-cell mediator through purinergic receptors after in vitro injury. However, the mechanism of interleukin-1Beta release after traumatic brain injury remains poorly defined and is difficult to study using in vivo models. Using an in vitro model for traumatic brain injury (cell strain or stretch), we investigated the role of the extracellular nucleotides (ATP) in regulation of interleukin-1Beta release in rat cortical brain cells. We now report that activated microglia constitute the major source of interleukin-1Beta release after in vitro trauma. ATP is a powerful stimulus for interleukin-1Beta release from microglial cultures. Glutamate inhibits interleukin-1Beta release. ATP-induced interleukin-1Beta release was blocked completely by the P2X7 receptor antagonist, oxidized ATP, and partially by the P2X7 receptor antagonist suramin, suggesting that ATP stimulates interleukin-1Beta release from microglia via purinergic receptor and the P2X7 receptor is responsible for the interleukin-1Beta release. Blockage of interleukin-1Beta release by the purinergic receptor antagonists oATP and suramin decreased cell damage in uninjured mixed organotypic brain cell culture exposed to activated microglia. Taken together, these results suggest that interleukin-1Beta mediated inflammatory events are regulated in activated microglia by extracellular nucleotides (ATP) via purinergic receptors in central nervous system after in vitro trauma.
| Identifer | oai:union.ndltd.org:ucf.edu/oai:stars.library.ucf.edu:etd-1138 |
| Date | 01 January 2004 |
| Creators | Liang, Chengya |
| Publisher | STARS |
| Source Sets | University of Central Florida |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Electronic Theses and Dissertations |
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