The choroid plexus, a region of brain tissue that produces cerebrospinal fluid (CSF), is an often-overlooked cranial powerhouse. But now, research conducted in the lab of Maria Lehtinen, Ph.D., at Boston Children’s Hospital, has shown that the choroid plexus plays a more important role than previously assumed. In fact, the tissue could potentially influence long-term brain health. A recent study led by Huixin Xu, Ph.D., a researcher in Lehtinen’s lab, shows how the choroid plexus manages brain inflammation by collaborating with immune cells. The team’s observations were published in Cell and could have lasting implications for neurological research.
How the Choroid Plexus Impacts Brain Inflammation
To evaluate the complex role of the choroid plexus, Xu’s team studied the response to inflammation in a mouse model mimicking a meningitis infection. Specifically, the researchers used intracerebroventricular injections of lipopolysaccharides, also known as LPS, to model meningitis in mice. Then, to get a window into the brain, the team carefully replaced a section of the skull with a piece of clear plexiglass. This allowed the team to observe the choroid plexus in real time as the modeled infection created advanced inflammation in the brain. The team also used single-cell RNA sequencing to analyze the role of each cell type in the choroid plexus during the course of the infection.
The Role of Epithelial Cells in Brain Inflammation
During the observation period with the LPS mouse models of meningitis, the researchers noted new immune cells from the blood — monocytes and macrophages, specifically, which are immune cells that help to stem brain inflammation throughout the course of an infection — entering the CSF through the choroid plexus. Crucially, the team observed epithelial cells in the choroid plexus physically coordinating the tissue’s response to the infection, orchestrating the arrival of these immune cells. The epithelial cells first created an opening for the immune cells to pass through; eventually, the epithelial cells issued signals to “recruit” the monocytes and macrophages. The epithelial cells also secreted sticky adhesion molecules to help the immune cells “dock” near and on the choroid plexus. After the inflammation was resolved, the immune cells left the choroid plexus, ending the complex “choreography” that took place within the tissue supported by epithelial cells.
“The choroid plexus is kind of like a conductor — orchestrating this symphony of a response,” noted Lehtinen, the head of the lab. “I never imagined epithelial cells would be able to organize these things. Technological advances allowed us to uncover this exciting biology that no one ever expected.”
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Ultimately, these observations led Lehtinen to classify the choroid plexus as more than brain tissue. According to Lehtinen, the tissue serves as a genuine immune organ and should be studied as an indicator for possible future treatments in instances of brain inflammation. Now, the researchers are empowered to explore the tissue’s role in different disease settings — for example, neurologic conditions ranging from long COVID to Alzheimer’s, both of which involve brain inflammation. “This study gives us a pretty clean, contained way of showing the steps of inflammation,” says Xu. “It provides a backbone that we can then apply to see what happens in neurodegenerative and neurodevelopmental diseases.” Moving forward, the researchers may apply their findings to further animal models of disease to pinpoint therapeutic applications.
To explore the effects of LPS treatments, Scantox Neuro offers both in vitro and in vivo preclinical models. In vitro, LPS can be used to stimulate neuroinflammation in various types of cell culture models. In vivo, mice are treated with LPS to induce neuroinflammation. Analysis of neuroinflammation can be performed by measuring cytokine levels or histologically by labelling and quantifying different inflammation-related biomarkers, such as GFAP, Iba1, CD68, and many more. Furthermore, in vivo CSF of mice can be sampled repeatedly to evaluate the progression of neuroinflammation and other biomarkers in the same animal over time.
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