Roles of interleukin-1 beta in glutamate-induced spinal cord injury
| dc.contributor.advisor | David McAdoo | en_US |
| dc.contributor.committeeMember | Raymond Grill | en_US |
| dc.contributor.committeeMember | Ping Wu | en_US |
| dc.contributor.committeeMember | Allan Brasier | en_US |
| dc.contributor.committeeMember | Alex Kurosky | en_US |
| dc.creator | Song Liu | en_US |
| dc.date.accessioned | 2011-12-20T16:05:33Z | |
| dc.date.available | 2009-06-09 | en_US |
| dc.date.available | 2011-12-20T16:05:33Z | |
| dc.date.created | 2006-11-17 | en_US |
| dc.date.issued | 2006-11-15 | en_US |
| dc.description.abstract | Glutamate release contributes to the impairments caused by spinal cord injury (SCI). This study addresses the mechanisms of glutamate toxicity involving activation of interleukin-1â (IL-1â). To assess the effects of glutamate on IL-1â and its natural blocking agent interleukin-1 receptor antagonist (IL-1ra), ELISA assays were used to measure the responses of endogenous IL-1â and IL-1ra to glutamate administered to the spinal cord. Levels of activated IL-1â and IL-1ra changed in a reciprocal fashion starting 1 hour after glutamate exposure. Exposure to glutamate initially increases IL-1â expression while it decreases IL-1ra. IL-1â then decreases and IL-1ra increases. IL-1â and IL-1ra change reciprocally in the same fashion in a contused spinal cord. To check whether this mutual effect is due to actions of IL-1â and IL-1ra on each other, IL-1â was applied on the spinal cord and then IL-1ra was measured. IL-1ra was applied onto the cord and IL-1â was measured as well. The results show that administration of IL-1â stimulates the production of IL-1ra and administration of IL-1ra suppresses the activation of IL-1â. To identify subtypes of glutamate receptors involved in this phenomenon, NMDA and AMPA receptor agonists were separately applied to the spinal cord and IL-1â and IL-1ra expression in the cord were measured with ELISA assays. Activation of both the AMPA and the NMDA receptors also induced reciprocal changes between the IL-1â and IL-1ra levels. To determine the effects of activating AMPA and NMDA receptors on IL-1â and IL-1ra, MK801 and NBQX were applied individually on the spinal cord with glutamate. The results show that both AMPA and NMDA receptors are involved in glutamate-induced reciprocity between IL-1â and IL-1ra. To determine if this reciprocity between the expression of IL-1â and IL-1ra affected post-SCI locomotor function, recombinant IL-1â and IL-1ra were administered to glutamate-exposed spinal cords. The Basso-Beattie-Bresnahan (BBB) test of functional recovery demonstrated that IL-1â impaired rat locomotive ability and that IL-1ra improved the recovery of the rats from glutamate-induced locomotor impairment. To explore the mechanism of this IL-1â involvement in excitotoxicity, MAPK activities responding to glutamate were measured and the results showed that both ERK1/2 and p38 are involved in IL-1â induced SCI. Cell death assays showed that apoptosis is caused by glutamate-induced SCI. Overall, we established the following pathway from spinal cord injury to functional impairment: SCI → glutamate release → IL-1â and IL-1ra changes → ERK1/2 and p38 activation → cell death → functional impairment. This is the first pathway traced from glutamate release to functional impairments. | en_US |
| dc.format.medium | electronic | en_US |
| dc.identifier.other | etd-11172006-151805 | en_US |
| dc.identifier.uri | http://hdl.handle.net/2152.3/260 | |
| dc.language.iso | eng | en_US |
| dc.rights | Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works. | en_US |
| dc.subject | spinal cord injury | en_US |
| dc.subject | MAPKs | en_US |
| dc.subject | IL-1ra | en_US |
| dc.subject | IL-1â | en_US |
| dc.subject | glutamate | en_US |
| dc.title | Roles of interleukin-1 beta in glutamate-induced spinal cord injury | en_US |
| dc.type.genre | dissertation | en_US |
| dc.type.material | text | en_US |
| thesis.degree.department | Biochemistry and Molecular Biology | en_US |
| thesis.degree.grantor | The University of Texas Medical Branch | en_US |
| thesis.degree.level | Doctoral | en_US |
| thesis.degree.name | PhD | en_US |