Stroke; a journal of cerebral circulation
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Comparative Study
Sex differences in the response to poly(ADP-ribose) polymerase-1 deletion and caspase inhibition after stroke.
Emerging data suggest that the molecular cell death pathways triggered by ischemic insults differ in the male and female brain. Cell death in males is initiated by poly(ADP-ribose) polymerase-1 (PARP-1) activation; however, manipulation of this pathway paradoxically increases ischemic damage in females. In contrast, females are exquisitely sensitive to caspase-mediated cell death. The effect of caspase inhibition in PARP-1 knockout mice was evaluated to determine if the detrimental effects of PARP deletion in females were secondary to increased caspase activation. ⋯ Deletion of PARP-1 reduces infarct in males but exacerbates injury in females. PARP-1(-/-) females have enhanced caspase activation. The detrimental effects of PARP loss in females can be reversed with caspase inhibition.
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Randomized Controlled Trial Comparative Study
Subtherapeutic warfarin is not associated with increased hemorrhage rates in ischemic strokes treated with tissue plasminogen activator.
Concern exists that preadmission warfarin use may be associated with an increased risk of intracerebral hemorrhage in patients with ischemic stroke receiving intravenous tissue plasminogen activator, even in those with an international normalized ratio <1.7. However, evidence to date has been derived from a small single-center cohort of patients. ⋯ The results from the present study suggest that tissue plasminogen activator treatment appears to be safe in patients with acute ischemic stroke taking warfarin with an international normalized ratio <1.7 and may reduce the risk of poor functional outcome.