It is increasingly recognized that histological and functional outcomes after stroke are shaped by biologic sex. Emerging data suggests that ischemic cell death pathways are sexually dimorphic (Hurn et al., 2005; Lang and McCullough, 2008). Reducing neuronal nitric oxide (NO) or poly-ADP ribose polymerase (PARP-1) activation protects only the male brain (Hagberg et al., 2004), and paradoxically enhances ischemic injury in females (McCullough et al., 2005). In this study, we examined downstream mediators of NO/PARP activation to investigate possible mediators of ischemic sexual dimorphism. Nuclear translocation of Apoptosis Inducing Factor (AIF) was equivalent in wild-type males and females after stroke and was unaffected by estrogen exposure. Deletion of PARP1 led to a dramatic reduction in stroke-induced poly(ADP-ribose) polymerase (PAR) formation and AIF translocation in both sexes, yet ischemic damage was reduced only in males. Subsequent examination of AIF-deficient Harlequin mice demonstrated that male Harlequin mice had less PAR formation, reduced AIF translocation and less ischemic damage than male wild-type mice. In contrast, female Harlequin mice had no neuroprotective effect of gene deletion despite robust reductions in PAR formation and AIF translocation. Although equivalent activation of this cell death pathway occurs in both sexes after ischemia, detrimental effects are only present in males. AIF translocation and PAR formation do not mediate ischemic injury in the female brain, therefore agents designed to reduce PARP1 activation are unlikely to benefit females.

Stroke is a leading cause of permanent disability and death. It is well accepted that the principal mammalian estrogen (E2), 17-b estradiol, provides robust neuroprotection in a variety of brain injury models in animals of both sexes. E2 enhances neurogenesis after stroke in the subventricular zone; however, it is unknown if these cells survive long-term or enhance functional recovery. In this study, we examined stroke-induced neurogenesis in male, gonadally intact female, and ovariectomized female mice 2 and 6 weeks after stroke. Treatment with 17-b estradiol increased 5-bromo-2 0 -deoxyuridine-labeled cells at both time points in both the dentate gyrus and subventricular zone; the majority were colabeled with doublecortin at 2 weeks and with NeuN at 6 weeks. Stroke-induced neurogenesis was reduced in estrogen receptor knockout mice, as well as in mice lacking the gene for aromatase, which converts testosterone into E2. Improved behavioral deficits were seen in E2-treated mice, suggesting that E2-induced increases in poststroke neurogenesis contribute to poststroke recovery.

No abstract

Children with cerebral palsy and other neurologic diseases often present with sialorrhea. Intraglandular botulinum neurotoxin is being increasingly reported to be clinically effective for the treatment of sialorrhea. This treatment is becoming more popular in recent years because of being less invasive than surgical procedures. In addition, fewer adverse effects have been documented compared with oral or topical anticholinergic medication. We report the first case in a child with cerebral palsy who developed serious acute sialadenitis with submandibular sialolithiasis after intraglandular botulinum neurotoxin injection for sialorrhea.