beta-amyloid peptide (Abeta) has been implicated in the pathogenesis of Alzheimer disease and has been reported to induce apoptotic death in cell culture. Cysteine proteases, a family of enzymes known as caspases, mediate cell death in many models of apoptosis. Multiple caspases have been implicated in Abeta toxicity; these reports are conflicting. We show that treatment of cerebellar granule cells (CGC) with Abeta25-35 causes apoptosis associated with increased activity of caspases-2, -3 and -6. Selective inhibition of each of these three caspases provides significant protection against Abeta-mediated apoptosis. In contrast, no change in caspase-1 activity was seen after Abeta25-35 application, nor was inhibition of caspase-1 neuroprotective. Similar to CGC, cortical neuronal cultures treated with Abeta25-35 demonstrate increased caspase-3 activity but not caspase-1 activity. Furthermore, significant neuroprotection is elicited by selective inhibition of caspase-3 in cortical neurons administered Abeta25-35, whereas selective caspase-1 inhibition has no effect. Taken together, these findings indicate that multiple executioner caspases may be involved in neuronal apoptosis induced by Abeta.
Background. Patients undergoing aortic arch replacement are at high risk for neurologic injury. This study compared two different established neuroprotective strategies in patients undergoing elective transverse hemiarch replacement. Methods. Twenty patients undergoing hemiarch replacement were prospectively randomized to receive deep hypothermic circulatory arrest with retrograde cerebral perfusion (DHCADRCP) or moderate hypothermic circulatory arrest with antegrade cerebral perfusion (MHCADACP). All patients received neurologistadjudicated examinations and magnetic resonance imaging before discharge. The primary end point was a composite of stroke, transient ischemic attack, and magnetic resonance imaging-adjudicated injury. Secondary end points were transient neurologic dysfunction, and the National Institutes of Health Stroke Scale, and neurocognitive scores. Results. Randomization resulted in 11 DHCADRCP patients and 9 MHCADACP patients. There was no difference in cardiopulmonary bypass, cross-clamp, or circulatory arrest times. MHCADACP patients underwent
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