Intracranial aneurysms are defined as pathological dilatations of cerebral arteries and rupture of intracranial aneurysms leads to subarachnoid hemorrhage (SAH). The goal of this review was to outline the sex differences in the formation and progression of intracranial aneurysms as well as sex-related differences in incidence and outcome of SAH. The literature review was performed using PubMed with a combination of these search terms: "subarachnoid hemorrhage," "incidence," "outcome," "sex," "gender," "male," "female," "experimental," "mice," and "rats." Studies written in English were used. Female sex is thought to be a risk factor for aneurysm formation, especially in postmenopausal age populations, suggesting the potential protective involvement of sex steroids. Female sex is also considered a risk factor for SAH occurrence. Although incidence and mortality are confirmed to be higher in females in most studies, they elucidated no clear differences in the functional outcome among SAH survivors. The effect of gender on the pathophysiology of SAH is not very well understood; nevertheless, the majority of pre-clinical studies suggest a beneficial effect of sex steroids in experimental SAH. Moreover, conflicting results exist on the role and effect of hormone replacement therapies and oral contraceptive pills on the incidence and outcome of human SAH. Sex differences exist in the formation of aneurysms as well as the incidence and mortality of SAH. Potential therapeutic effects of sex steroids have been replicated in many animal studies, but their potential use in the treatment of acute SAH in human populations needs more future study.

The most important aspect of a preclinical study seeking to develop a novel therapy for neurological diseases is whether the therapy produces any clinically relevant functional recovery. For this purpose, neurobehavioral tests are commonly used to evaluate the neuroprotective efficacy of treatments in a wide array of cerebrovascular diseases and neurotrauma. Their use, however, has been limited in experimental subarachnoid hemorrhage studies. After several randomized, double-blinded, controlled clinical trials repeatedly failed to produce a benefit in functional outcome despite some improvement in angiographic vasospasm, more rigorous methods of neurobehavioral testing became critical to provide a more comprehensive evaluation of the functional efficacy of proposed treatments. While several subarachnoid hemorrhage studies have incorporated an array of neurobehavioral assays, a standardized methodology has not been agreed upon. Here, we review neurobehavioral tests for rodents and their potential application to subarachnoid hemorrhage studies. Developing a standardized neurobehavioral testing regimen in rodent studies of subarachnoid hemorrhage would allow for better comparison of results between laboratories and a better prediction of what interventions would produce functional benefits in humans.

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