Introduction: Ischemic postconditioning provides protective effects against stroke and improves neurological deficits. Recent studies demonstrated that T-cell plays an 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 protective role of Akt/mTOR pathway in postconditioning.
Methods: Focal ischemia was induced by 30 min of transient bilateral CCAs 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 behavior test, home cage, vibrissa-elicited limb and postural reflex tests were performed until 30d after stroke. Peri-infarct and ischemic core tissues were collected for Western blotting. Protein levels of p-mTOR, p-S6K, p-4EBP-1, Akt and its isoforms (Akt1-3) were 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%, 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, p-4EBP1, both in the peri-infarct area and core 24h post-stroke. In addition, ischemic postconditioning improved neurological function when measured 30d post-stroke, 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.
Patient Care: This is a translational research, which showed the strong relationship among brain ischemia, immune system and postcondtioning. It will certainly be helpful to the cl
Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the strong relationship between stroke, immunse system and postconditioning. 2) Discuss, in small groups,about brain ischemia and imuunse system. 3) Identify an effective treatment for brain ischemia (such as clinical postcondtioning, immune suppression, etc).