Ischemic preconditioning (IP) protects the brain from subsequent, prolonged, and lethal ischemia in experimental studies. Erythropoietin (EPO) participates in the brain's intrinsic response to injury and may play a role in preconditioning. By using a middle cerebral artery occlusion (MCAo) model of transient ischemic attack (TIA), we sought to determine whether EPO is required for IP in the protective response against focal ischemic stroke. Rats underwent three 10-min MCA occlusions or sham surgery. Three days later, animals underwent 2 hr of MCAo and 22 hr of reperfusion. Experimental TIAs reduced infarct volumes by 55% (P < 0.05), inhibited DNA fragmentation, and improved neurological outcome by 50% (P < 0.05) after ischemic stroke. EPO and its receptor were up-regulated by IP in the ipsilateral hemisphere by 24 hr after IP, before ischemic stroke and soluble EPO receptor attenuated neuroprotection by IP (88% reduction, P < 0.05). Pretreatment with the PI-3 kinase inhibitor wortmannin abolished the protective effect of IP against ischemic injury (P < 0.05). IP may be mediated in part by EPO through a PI-3 kinase pathway.
Our multifaceted program, designed to enhance resident and faculty engagement in scholarship, was associated with increased academic output and an expanded mentorship pool. The program was particularly effective at encouraging presentations at scientific meetings. Longitudinal analysis will determine whether such a program portfolio inspires an increase in academic careers involving neuroscience-oriented research.
Thrombolytic and antithrombotic agents form the cornerstone of stroke treatment and prevention. Recombinant tissue plasminogen activator improves outcome in patients treated within 3 hours of stroke onset. Emerging trials are directed to extend the therapeutic window and identify agents that could provide better safety profiles. Large, randomized trials have also highlighted the effectiveness and safety of early and continuous antiplatelet therapy in reducing atherothrombotic stroke recurrence. Aspirin has become the antiplatelet treatment standard against which several other antiplatelet agents have been shown to be more effective. The prevention of cardioembolic stroke is best accomplished with oral anticoagulation, barring any contraindications.
Stroke continues to be a major cause of adult mortality and disability. After numerous clinical trials and hundreds of millions of dollars spent on research, only two drugs are effective in treating patients with acute stroke. Recombinant tissue-plasminogen activator improves the chance of an excellent outcome in treated patients by 30%. Danaparoid sodium improves the chance of a very favorable outcome in treated patients with stroke due to large artery atherosclerosis. Although acute treatments are limited, our understanding of stroke pathogenesis and the importance of preventing poststroke complications has improved patient outcome significantly.
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