The role of inflammation and potential use of sex steroids in intracranial aneurysms and subarachnoid hemorrhage

Abstract

Background:Aneurysmal subarachnoid hemorrhage (aSAH) continues to be a devastating neurological condition with a high risk of associated morbidity and mortality. Inflammation has been shown to increase the risk of complications associated with aSAH such as vasospasm and brain injury in animal models and humans. The goal of this review is to discuss the inflammatory mechanisms of aneurysm formation, rupture and vasospasm and explore the role of sex hormones in the inflammatory response to aSAH.Methods:A literature review was performed using PubMed using the following search terms: “intracranial aneurysm,” “cerebral aneurysm,” “dihydroepiandrosterone sulfate” “estrogen,” “hormone replacement therapy,” “inflammation,” “oral contraceptive,” “progesterone,” “sex steroids,” “sex hormones” “subarachnoid hemorrhage,” “testosterone.” Only studies published in English language were included in the review.Results:Studies have shown that administration of sex hormones such as progesterone and estrogen at early stages in the inflammatory cascade can lower the risk and magnitude of subsequent complications. The exact mechanism by which these hormones act on the brain, as well as their role in the inflammatory cascade is not fully understood. Moreover, conflicting results have been published on the effect of hormone replacement therapy in humans. This review will scrutinize the variations in these studies to provide a more detailed understanding of sex hormones as potential therapeutic agents for intracranial aneurysms and aSAH.Conclusion:Inflammation may play a role in the pathogenesis of intracranial aneurysm formation and subarachnoid hemorrhage, and administration of sex hormones as anti-inflammatory agents has been associated with improved functional outcome in experimental models. Further studies are needed to determine the therapeutic role of these hormones in the intracranial aneurysms and aSAH.

Profiling of immune infiltration landscape of ruptured intracranial aneurysm

“…Evidence from numerous studies shows that immune cells participate in initiation of IA by triggering production of molecules that initiate inflammation, as well as factors that induce pathological remodeling of vasculature. [30][31][32][33] The data of the selected samples were classified and analyzed by considering IA rupture as an independent factor and identified 10 hub genes that form part of early processes that lead to IA rupture. Moreover, association of immune cell infiltration with IA rupture was established in the current study where several immune-related signaling pathways involved in IA rupture were revealed.…”

Associations between Inflammatory Cytokine Gene Polymorphisms and Susceptibilities to Intracranial Aneurysm in Chinese Population

“…Studies have found that there is a large amount of inflammatory cell infiltration in IA tissues, and the levels of inflammatory cytokines in the cerebrospinal fluid of SAH are significantly increased, but there is no infiltration of inflammatory cells in the normal arterial wall [ 8 – 11 ]. The mechanism of inflammation involved in IA may be related to the inflammation-induced vascular endothelial damage, the degenerative vascular wall remodeling, and a high blood flow, including increased vascular wall shear stress [ 12 , 13 ]. Candidate gene association studies revealed that polymorphisms in interleukin 1 ( IL1 ), interleukin 6 ( IL6 ), interleukin 12 ( IL12 ), and tumor necrosis factor- α ( TNF-α ) genes are associated with IA in several populations [ 14 – 17 ].…”

Underlying mechanism of hemodynamics and intracranial aneurysm

“…Till now, the etiology of IA remains to be clarified; the genetic aspect, living habit, environment, and estrogen hormone are all reported to be closely related to IA development [3][4][5]. Among the potential risk factors of IA, abnormal hemodynamics is one of the location-specific dangerous factors, which show high relevance with vessel inflammation and atherosclerotic plaque [6].…”