MS, along with many other neurological diseases, is partially characterized by permeability of the blood-brain barrier (BBB). This barrier is comprised of blood vessels and associated cells that are responsible for tightly controlling precisely what nutrients, proteins, and other molecules are granted access to the privileged environment of the brain. While the role of the BBB in health and disease is widely accepted, we still have much to learn about how it typically protects the central nervous system and what goes wrong when it fails to do so. It may come as a surprise that gender is something we cannot afford to ignore in our ongoing quest to understand BBB functionality.
An emerging topic in various areas of brain research is sexual dimorphism, referring to biological divergence between women and men. Recent studies have detected sex-based differences at the molecular level in common behaviors including cognitive tasks, expression of empathy, and response to acute stress. Given the increased incidence of MS in women but greater disease severity in men, sexually dimorphic features of the nervous system are especially compelling.
One neurology group from Sweden conducted a massive study involving over 20,000 patients with diagnosed neurological disorders and 335 healthy volunteers that revealed sexual dimorphism in BBB integrity in both groups. The researchers relied on a metric called the CSF/serum albumin ratio to quantify BBB integrity. Albumin is a protein produced in the liver that should not have access to the CNS and should therefore be absent in cerebrospinal fluid (CSF). The presence of albumin in CSF is often interpreted as a sign of BBB permeability. Thus, the higher the ratio, the more intact the BBB, and vice versa.
Interestingly, the Swedish group found that females had higher CSF/serum albumin ratios meaning greater BBB integrity than males over the majority of the lifespan. The difference was not present at birth, but became apparent around 6 years and persisted through old age. This trend applied to neurological patients and healthy controls alike.
Although there are certainly numerous factors contributing to MS prevalence and disease progression, the concept of sexual dimorphism is providing some exciting insight into the mechanisms underlying MS and other similar diseases. In the Vartanian lab, we currently study the effects of steroid hormones produced in the brain, such as progesterone, on MS lesion formation and repair. As the field of sexual dimorphism in the context of the brain is a rapidly evolving one, we are eager to harness the accumulating data to enhance our understanding of MS pathology, and why it differs according to gender. Ultimately, the hope is to minimize the overall disease burden by developing innovative treatment options optimized for specific groups of people, in this case, women and men.
Reference:
Parrado-Fernández C, Blennow K, Hansson M, Leoni V, Cedazo-Minguez A, Björkhem I.
Evidence for sex difference in the CSF/plasma albumin ratio in ~20 000 patients and 335 healthy volunteers. J Cell Mol Med. 2018;00:1-4. https://doi.org/10.1111/jcmm.13767
by Paige Winokur