Grant: Project Grant

Pannexin 1 (Panx1) is a protein found in the membrane of various cell types, including neurons, to assist in the passage or communication of very small molecules. Ischemic injuries that deprive neurons of oxygen and glucose (e.g. stroke) can enhance the activity of Panx1 to promote cell death (apoptosis). Men and women often show differences in stroke severity to suggest a potential role for the gonadal steroid hormones, estradiol and testosterone. Because Panx1 can mediate apoptosis and inflammatory signaling responses in injured neurons, we reason that it may come to explain sex differences in stroke outcome responses. Indeed, in our brain stroke model we have evidence to show that either the loss of the Panx1 gene or its pharmacological blockade significantly reduce the amount of neuronal damage in female, but not in male mice. This striking difference underscores Panx1 as an important focal point for unmasking underlying gonadal hormone and cellular mechanisms mediating sexual dimorphisms in stroke severity, as we propose to examine in the current application. The findings of this grant promise to provide novel frameworks for sex- and age-dependent differences in stroke vulnerability and rescue.