Abstract 96: Ischemic Postconditioning Did Not Attenuate Acute Infarction But Improved Long-term Outcomes By Promoting mTOR Activity In Nude rats
Introduction: Ischemic postconditioning provides protective effects against focal ischemia and improves neurological deficits. Recent studies have shown that T cells play important roles in stroke. In this study, we investigated whether postconditioning protects against stroke in nude rats with T-cell deficiency, and examined the potential role of mTOR pathway in the protective effects of postconditioning.
Methods: Focal ischemia was induced by 30min of transient bilateral CCA occlusion and permanent distal MCA occlusion in nude rats with T-cell deficiency (RNU rats, Charles River). Ischemic postconditioning was conducted immediately after reperfusion by 3 cycles of 30 sec reperfusion and 10 sec occlusion of the bilateral CCAs. Rapamycin, an mTOR inhibitor, was injected into the left lateral ventricle 1h before stroke. For the behavior test, home cage, vibrissa-elicited limb use and postural reflex tests were performed until 30d after stroke. Peri-infarct and ischemic core tissues were collected 1, 5, 9 and 24h after stroke for Western blotting. Protein levels of p-mTOR, S6K, 4EBP-1, Akt and its isoforms (Akt1-3) were also measured.
Results: Different from wild type rats, the cortical infarction induced by stroke was not significantly reduced by postconditioning in nude rats when measured 2d post-stroke (27.1±4.3% in control ischemia vs 23.7±4.2% in postconditioning, n=6). Despite the unaltered infarct size, Western blot showed that postconditioning significantly increased the protein levels of p-Akt, Akt isoforms, p-mTOR, p-S6K and p-4EBP1, both in the peri-infarct area and core 24h after stroke (p<0.05). In addition, postconditioning improved neurological function when measured 30d after stroke (n=6, p<0.05), and reduced brain damage size from 10.2±1.4% to 4.9±1.6% (n=6, p<0.05). The mTOR inhibitor, rapamycin, significantly attenuated p-mTOR and p-S6K levels both in the peri-infart area and core at 1, 5, 9 and 24h after stroke (p<0.05), and abolished the long-term protective effects of postconditioning.
Conclusions: Ischemic postconditioning did not inhibit acute infarction but provided long-term protection by enhancing Akt and mTOR activity in the acute phase after stroke in nude rats.
- © 2012 by American Heart Association, Inc.