Sex Specific Ischemic Cell Signaling
Patricia D. Hurn, Ph.D. – Principal Investigator

Stroke is a sexually dimorphic disease, and we now know that molecular pathways leading to cell death are gender-specific.  Our new data shows that, activation of the poly (ADP-ribose) polymerase gene (PARP-1) plays a decisive role in the mechanism of pathogenesis from ischemic injury in the male mouse brain.  One might expect, therefore, that, in the absence of PARP, outcome from ischemic injury would be correspondingly improved.  On the contrary, we found that, in female mice, ischemic damage is not decreased, but rather, it is enhanced if the action of PARP is removed by genetically deleting PARP-1 or by using PARP inhibitors.  This sex difference cannot be explained by estrogenic actions.

In these studies, we break new ground by focusing on how testosterone and its androgen receptor account for sex-specific PARP-1 cell-death signaling.

This research is funded by the Bugher Foundation of the American Heart Association.