Scientists study the impact of biological sex on brain barrier and neurodevelopment in newborns
The research, led by the University of Coimbra, aims to better understand the increased susceptibility of male newborns to infection and its impact on neurodevelopment, paving the way for new therapies to prevent health complications in the first days of life.
A research team from the University of Coimbra (UC) is studying the brain of newborns to understand how biological sex influences neurodevelopment and susceptibility to infections.
This research builds on clues from previous scientific studies suggesting that male newborns are at higher risk of conditions such as sepsis—an uncontrolled, systemic immune response to infection that can cause organ damage and, if not treated promptly, lead to multiple organ failure and death. The UC team aims to gain a deeper understanding of this process, thus paving the way for new therapies to prevent health complications in the first days of life.
The project BarriersReveal – "Desvendar o papel do sexo nas barreiras cerebrais durante o período neonatal" [ Unveiling how sex influences brain barriers in the neonatal period], will run for one and a half years and is coordinated by Vanessa Coelho-Santos, a researcher at the Coimbra Institute for Biomedical Imaging and Translational Research (CIBIT) of the Institute for Nuclear Sciences Applied to Health (ICNAS), who focuses her research on the neonatal brain, which covers the first 28 days of a baby's life.
According to Vanessa Coelho-Santos: "Scientific studies have shown that male infants and children have a higher risk of developing neurodevelopmental disorders such as autism and hyperactivity, which are often associated with neonatal infections and neuroinflammation." However, she stresses: "We still do not fully understand how biological sex physiologically affects the maturation of blood vessels and brain barriers or the neuroimmune system, or how these factors contribute to male susceptibility to certain disorders - and why females tend to be more resilient; this is what we want to find out in our research.
Commenting on the importance of studying the brain immediately after birth, the scientist says: "The neonatal brain is particularly vulnerable because of the intense vascular growth and maturation of the blood-brain barrier, but also because of the immature immune system that protects our brain. Given these vulnerabilities, it is crucial to gain a deep understanding of the effects of these physiological growth processes, so that in the future we can develop interventions to prevent the progression of problems that may arise during this critical period of brain development”.
In this context, the team is studying the brain barriers that regulate communication with the peripheral system. These include the meninges, which surround and protect the brain and also house immune cells; the blood-brain barrier, which acts as a protective filter for substances and cells from the bloodstream into the brain; and the choroid plexus, which produces the fluid that surrounds and protects the brain and also helps to regulate immune responses. These structures play a critical role in protecting the brain and shaping how it responds to infection, toxins and inflammation in the first days of life.
This preclinical study in laboratory mice aims to analyse the immunological composition and maturation of different brain barriers in male and female newborns. " As there is no molecular data from humans yet, the study will start with preclinical models and later compare the results with human tissue," explains Vanessa Coelho-Santos.
To collect brain data, the researchers will use real-time brain imaging using two-photon microscopy - a cutting-edge imaging technique that provides high-resolution images over time. They will also use flow cytometry, a laboratory technique that allows detailed analysis of different cellular properties. "These interfaces will be studied comparatively in newborn male and female mice to identify sex differences and understand how these different characteristics contribute to the well-documented greater male susceptibility to infection and neurodevelopmental disorders," the UC researcher explains.
The study is funded by the Portuguese Foundation for Science and Technology with approximately €50,000 and involves collaboration with Juliane Gust, a physician and researcher at Seattle Children's Research Institute.