Sex—like age, weight, and underlying health conditions—is a biological variable that is often a critical factor when it comes to health. However, sex has been largely absent in research and this has led to an incomplete understanding of sex-based differences in disease processes and treatment therapies that are appropriate for men and women.

Ischemic stroke is one of the diseases for which a lack of preclinical data on male and female subjects presents a critical gap in information for clinical researchers who are testing therapies in women and men.

A new study led by Halina Offner, Dr. Med., shines some light on the ways immune systems in female and male mice respond differently to ischemic stroke. The study was published in Cellular Immunology. Offner, OHSU professor of neurology, and immunologist at the Veterans Affairs Medical Center, and her team see this as an important step in developing effective treatments. In this case, successful therapies will be sex-specific.

Investigators examined the integration of the spleen—a major component of the immune system—in the regulation of immune responses in the brain and throughout the body. The severity of the stroke was measured using digital imaging, and levels of immune-related cells were measured and analyzed with a Cellometer cell counter and flow cytometry analysis.

The study demonstrated two important differences in immune regulation in male and female mice. Female mice had higher levels of regulatory B cells, which help suppress responses, but had lower levels of anti-inflammatory macrophages, another immune cell. These results make clear mechanisms that account for less severe strokes in females and also explain why immune-modulating therapies, like splenectomy, protect male animals but not female animals.

This research, supported by a 2012–2016 NIH grant, underscores the importance of testing therapies for stroke in both males and females. Beginning in January 2016, the NIH began ensuring that researchers account for sex as a biological variable in studies with vertebrate animals and humans. Closing the gaps in preclinical knowledge will provide scientific data to help improve treatments and recovery of women and men.

In addition to Offner and first author Hilary Seifert, Ph.D., (log-in required) co-authors include Gil Benedek, Jian Liang, Ha Nguyen, Gail Kent, Arthur Vandenbark, and Julie Saugstad. This work was supported by NIH/National Institute of Neurological Disorders and Stroke 1RO1 NS075887 (H.O.) and 1RO1 NS076013 (H.O., J.S.) and the American Heart Association 17GRNT33220001 (H.O).