Neuroscience 2003 Abstract
| Presentation Number: | 741.15 |
|---|---|
| Abstract Title: | Expanded therapeutic window for SKI-606, a novel Src kinase inhibitor, in rat transient focal ischemia. |
| Authors: |
Gonzales, C.*1
; Xiao, Y.1
; Liang, S.1
; Dilks, D.1
; Ye, F.
; Boschelli, D.
; Boschelli, F.
; Pong, K.1
; Zaleska, M. M.1
1Neurosci., Wyeth Res., Princeton, NJ |
| Primary Theme and Topics |
Neurological and Psychiatric Conditions - Ischemia -- Neuroprotection and tolerance |
| Session: |
741. Ischemia: Neuroprotection & Tolerance - Treatment Poster |
| Presentation Time: | Tuesday, November 11, 2003 3:00 PM-4:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # JJ5 |
| Keywords: | STROKE, NEUROPROTECTION, MCAO, VASOGENIC EDEMA |
Focal cerebral ischemia in rodents and ischemic stroke in humans induce expression of vascular endothelial growth factor (VEGF), a major promoter of vascular permeability (VP) leading to brain edema and potential deterioration of clinical outcome. We have shown that a novel Src kinase inhibitor (Golas et al., Cancer Res. 2003, 63:375) provides effective neuroprotection from ischemic injury induced by a transient occlusion of the middle cerebral artery (tMCAO) when administered as a single i.v. bolus at 30 min post-MCAO (Zaleska et al., SFN 2003). The goal of the current study was to evaluate the therapeutic window for Src inhibition by SKI-606. Wistar rats subjected to a 90 min tMCAO using an intraluminal suture approach were treated with a single bolus dose of 10 mg/kg of SKI-606 administered i.v. at 0.5, 1.5, 3, 4, 5, or 6 hours post-MCAO. Neurological deficits and body weight loss/gain were evaluated over the course of 48 hours. Infarct volumes were assessed by TTC staining. A single dose treatment with SKI-606 was equally efficacious in reducing brain injury (infarct volume decrease by 41-64%) when administered up to 4 hours post-MCAO. Moreover, a significant protection from neurological deficits and post-stroke weight loss was observed with 5-6 hours window. These results strengthen the evidence that SKI-606 has potential as a therapeutic agent for the treatment of ischemic injury within a clinically relevant time window for human stroke.
<B>Conflict of Interest:</B> All authors are employed by Wyeth Pharmaceuticals.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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