Neuroscience 2003 Abstract
| Presentation Number: | 738.10 |
|---|---|
| Abstract Title: | Neuroprotective effect of the 2-aminotetraline derivative ST1942 on ischemia / reperfusion brain injury. |
| Authors: |
De Simoni, M.*1
; Echart, C.1
; Marzorati, P.1
; Storini, C.1
; Rossi, E.1
; Piovesan, P.2
; Ghirardi, O.2
1Dept. Neurosci, Inst. Mario Negri, 20157 Milano, Italy 2Italy, Via Eritrea 62, |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Ischemia -- Neuroprotection and tolerance |
| Session: |
738. Ischemia: Cell & Molecular Mechanisms - Cell Death III Poster |
| Presentation Time: | Tuesday, November 11, 2003 2:00 PM-3:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # FF6 |
| Keywords: | STROKE, INFLAMMATION, TUMOR NECROSIS FACTOR, INTERLEUKIN |
ST-1942 is a 2-aminotetraline derivative provided with anti-inflammatory properites (P. Piovesan, et al. 33rd SfN meeting).
Since ischemic brain injury is accompanied by a marked inflammatory reaction that contributes to the evolution of tissue injury, we set to determine the effect of ST1942 in a mouse model of ischemia/reperfusion.
Ischemia was induced by intraluminal occlusion of the middle cerebral artery (MCAO) in C57BL/6 mice. After 15 min, reperfusion was allowed by removing the nylon monofilament occluding the artery. The occurrence of ischemia was verified by laser doppler flowmetry and only mice showing >75% reduction of blood flow for the whole ischemic period were included in the study. ST 1942, at the dose of 25 mg/kg, or saline were injected intraperitoneally 30 min, 6, 24, 36 h from the beginning of ischemia. Ischemic volume was determined in the two experimental groups 48h later by neutral red staining and quantified by an Analyzing Image System. The results show that ST1942 significantly reduced infarct volume (ST1942: 5.6±2.0%, n=8; saline: 15.5±2.9%, n=8). To explore the mechanisms of action of the compound we then investigated the mRNA expression of inflammatory cytokines (IL-1β and TNFα). Real-time PCR was run on cortices of ischemic mice 4, 24 and 48h after ischemia, thus receiving 1, 2 and 4 doses of ST1942 (or saline), respectively. At each time point IL-1β and TNFα mRNA were significantly increased in ischemic compared to sham-operated mice. ST1942 treatment significantly counteracted the increase in both cytokines observed 24 and 48h after ischemia.
Thus ST1942 has a marked protective effect in ischemia/reperfusion brain injury, possibly related to its ability to counteract the upregulation of inflammatory cytokines.
Since ischemic brain injury is accompanied by a marked inflammatory reaction that contributes to the evolution of tissue injury, we set to determine the effect of ST1942 in a mouse model of ischemia/reperfusion.
Ischemia was induced by intraluminal occlusion of the middle cerebral artery (MCAO) in C57BL/6 mice. After 15 min, reperfusion was allowed by removing the nylon monofilament occluding the artery. The occurrence of ischemia was verified by laser doppler flowmetry and only mice showing >75% reduction of blood flow for the whole ischemic period were included in the study. ST 1942, at the dose of 25 mg/kg, or saline were injected intraperitoneally 30 min, 6, 24, 36 h from the beginning of ischemia. Ischemic volume was determined in the two experimental groups 48h later by neutral red staining and quantified by an Analyzing Image System. The results show that ST1942 significantly reduced infarct volume (ST1942: 5.6±2.0%, n=8; saline: 15.5±2.9%, n=8). To explore the mechanisms of action of the compound we then investigated the mRNA expression of inflammatory cytokines (IL-1β and TNFα). Real-time PCR was run on cortices of ischemic mice 4, 24 and 48h after ischemia, thus receiving 1, 2 and 4 doses of ST1942 (or saline), respectively. At each time point IL-1β and TNFα mRNA were significantly increased in ischemic compared to sham-operated mice. ST1942 treatment significantly counteracted the increase in both cytokines observed 24 and 48h after ischemia.
Thus ST1942 has a marked protective effect in ischemia/reperfusion brain injury, possibly related to its ability to counteract the upregulation of inflammatory cytokines.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
Copyright © 2003-2025 Society for Neuroscience; all rights reserved. Permission to republish any abstract or part of any abstract in any form must be obtained in writing by SfN office prior to publication.
