Friedrich Victor, Bederson Joshua B, Sehba Fatima A
Department of Neuroscience, Mount Sinai School of Medicine, New York, New York, United States of America.
PLoS One. 2013 Nov 8;8(11):e80101. doi: 10.1371/journal.pone.0080101. eCollection 2013.
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.
动脉瘤性蛛网膜下腔出血（SAH）患者早期死亡率很高。患SAH的女性多于男性，女性SAH幸存者的平均年龄大于男性幸存者；然而，尽管男性年龄较小，但其总体死亡率和神经功能结局并不比女性好。这种模式表明在初始冲击的严重程度和/或随后的病理生理学方面可能存在性别差异。我们通过血管内穿刺在年龄匹配的雄性和雌性大鼠中诱导蛛网膜下腔出血，探讨了生存和病理生理学方面的性别差异。在诱导SAH时及之后记录颅内压（ICP）、脑血流量（CBF）、血压（BP）和脑灌注压（CPP）。造模后3小时处死动物，研究蛛网膜下腔血肿大小、血管病理（胶原蛋白和内皮免疫染色）、炎症（血小板和中性粒细胞免疫染色）和细胞死亡（TUNEL检测）。在第二个队列中，测定24小时生存率。雄性大鼠的蛛网膜下腔血肿、出血后ICP峰值、血压升高、CPP降低、管腔内血小板聚集和中性粒细胞积聚、血管胶原蛋白丢失以及神经元和非神经元细胞死亡均比雌性大鼠更严重。血肿大小与凋亡细胞、血小板聚集体或中性粒细胞的数量无关。ICP峰值与血肿大小和凋亡细胞数量相关，但与血小板聚集体和中性粒细胞数量无关。这表明SAH时ICP升高的强度影响凋亡的严重程度，但不影响炎症的严重程度。雄性大鼠的死亡率明显高于雌性大鼠。我们的数据表明，在大鼠中，性别影响SAH的初始冲击，与雌性相比，雄性的出血和早期损伤更严重。
