Neuroscience 2003 Abstract
| Presentation Number: | 741.17 |
|---|---|
| Abstract Title: | Ski-606, a novel Src kinase inhibitor, improves long-term sensorimotor recovery after permanent focal ischemia. |
| Authors: |
Liang, S.*1
; Chen, Y.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 1:00 PM-2:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # JJ5 |
| Keywords: | STROKE, NEUROPROTECTION, MCAO, VASOGENIC EDEMA |
We have shown (Zaleska et al., SFN 2003 and Gonzales et al., SFN, 2003) that a suppression of Src kinase activity within several hours following a transient occlusion of the middle cerebral artery (tMCAO) reduces brain injury and neurological deficits, and protects from post-stroke weight loss as evaluated after 48 hours of reperfusion. The goal for the current study was to investigate whether post-stroke inhibition of Src can provide a long-term neurological benefit. Wistar rats were subjected to a permanent occlusion of the middle cerebral artery by electrocauterization (pMCAO), a model of focal ischemic stroke resulting in infarction in the sensorimotor cortex of the MCA territory. SKI-606, a potent novel Src kinase inhibitor (Golas et al., Cancer Res. 2003, 63:375) or vehicle was administered at 1.5, 4, 24 and 48 hours post-MCAO at 10 mg/kg i.v. Animals were evaluated in a postural test, visual and tactile forelimb foot placement and hindlimb placement tests (maximum neurological deficit score = 12) on days: 1, 2, 4, 7, 9, 11, 14, 16 and 21 by a researcher blinded to the treatments. SKI-606 significantly improved the recovery rate and provided a significant protection from neurological deficits on day 21 post-pMCAO. In summary, our work provides evidence that post-stroke inhibition of Src kinase with SKI-606 not only reduces ischemic injury but also diminishes development of long-term neurological deficits.
<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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