Gender Influences the Initial Impact of Subarachnoid Hemorrhage: An Experimental Investigation

Abstract

Aneurysmal subarachnoid hemorrhage (SAH) carries high early patient mortality. More women than men suffer from SAH and the average age of female SAH survivors is greater than that of male survivors; however, the overall mortality and neurological outcomes are not better in males despite their younger age. This pattern suggests the possibility of gender differences in the severity of initial impact and/or in subsequent pathophysiology. We explored gender differences in survival and pathophysiology following subarachnoid hemorrhage induced in age-matched male and female rats by endovascular puncture. Intracranial pressure (ICP), cerebral blood flow (CBF), blood pressure (BP) and cerebral perfusion pressure (CPP) were recorded at and after induction of SAH. Animals were sacrificed 3 hours after lesion and studied for subarachnoid hematoma size, vascular pathology (collagen and endothelium immunostaining), inflammation (platelet and neutrophil immunostaining), and cell death (TUNEL assay). In a second cohort, 24-hour survival was determined. Subarachnoid hematoma, post-hemorrhage ICP peak, BP elevation, reduction in CPP, intraluminal platelet aggregation and neutrophil accumulation, loss of vascular collagen, and neuronal and non-neuronal cell death were greater in male than in female rats. Hematoma size did not correlate with the number of apoptotic cells, platelet aggregates or neutrophil. The ICP peak correlated with hematoma size and with number of apoptotic cells but not with platelet aggregates and neutrophil number. This suggests that the intensity of ICP rise at SAH influences the severity of apoptosis but not of inflammation. Mortality was markedly greater in males than females. Our data demonstrate that in rats gender influences the initial impact of SAH causing greater bleed and early injury in males as compared to females.