Sex differences in preclinical ischemic stroke models

A systematic review and meta-analysis investigating sex differences in preclinical stroke research in in vivo and in vitro models. 

Background / Rationale

Sex differences in stroke incidence, severity, and outcomes have been observed in both clinical and preclinical studies. However, the underlying mechanisms of these differences remain poorly understood. In particular, the preclinical stroke research field has been criticized for its lack of consideration of sex as a biological variable, with the majority of studies conducted on male animals and little attention paid to potential sex-specific effects of experimental interventions. Therefore, there is a pressing need to evaluate and improve the reporting of sex in preclinical stroke research and to investigate the role of sex in stroke injury, protection, and repair.

Objectives

We will conduct a systematic review and meta-analysis of the existing preclinical stroke literature to evaluate sex differences in both in vitro and in vivo studies. This will include assessing the reporting of sex in in vitro studies, evaluating the sensitivity of male and female models to stroke injury, and investigating potential sex-specific effects of experimental therapies. Additionally, we aim to synthesize evidence on the mechanisms underlying sex differences in stroke injury, protection, and repair. Finally, we will develop a Systematic Online Living Evidence Summary (SOLES) of studies involving factors related to external validity in preclinical stroke research.

Methodology

To achieve our objectives, we will conduct a comprehensive search of the published literature using a predefined search strategy. We will include studies that meet our inclusion criteria, which will be developed based on a priori defined eligibility criteria. We will extract relevant data from each included study and conduct a meta-analysis where appropriate. We will use established risk of bias and study quality criteria to evaluate the quality of the included studies. Automated tools will be used to assess the reporting of sex in in vitro studies.

Expected Results / Implications / Perspectives

The results of this study will provide a comprehensive overview of sex differences in preclinical stroke research and identify areas where more research is needed. By highlighting the importance of considering sex as a biological variable in preclinical stroke research, we hope to encourage researchers to incorporate sex as a standard variable in their experimental design. This will ultimately lead to a better understanding of the mechanisms underlying sex differences in stroke injury, protection, and repair and facilitate the development of more effective sex-specific therapies. The development of a SOLES will provide a dynamic and continuously updated summary of the literature in this field and facilitate the translation of preclinical research findings into clinical practice.