At the Brain’s Edge: Researching the Meninges and their Role in Brain Health

Writing and photography by Ashleigh Willis from the Miller Lab, Michael Smith Laboratories

Sarah Ebert, a PhD candidate in the Miller lab at the Michael Smith Laboratories and the MacVicar lab at the Djavad Mowafaghian Centre for Brain Health, is investigating a fascinating structure that serves as a crucial boundary between the brain and body: the meninges.

PhD candidate Sarah Ebert smiles to camera, wearing a white lab coat and standing next to her work bench in the Miller lab.

Ebert standing beside her work bench in the Miller lab.

What are the meninges?
The meninges are layers of thin tissue that cover the brain and spinal cord, providing a barrier for the central nervous system. These layers are made of cells called “fibroblasts”, which are commonly found in connective tissues where they provide structure and support. There are three major layers of the meninges: the dura (a hard outer shell that sits next to the skull), the arachnoid (a weblike middle layer that functions as the barrier), and the pia mater (a delicate inner layer that sits next to the brain).

An immunostaining image from Ebert's research shows cells in red, covering the brain, which appears as blue shapes.

Immunostaining image from Ebert’s research showing the layers of meningeal cells (in red) covering the upper layers of the brain.

The meninges are a multi-functional tissue that cushions the brain, regulates nutrient flow and waste removal, and keeps harmful substances out of the brain by forming a tight barrier. The meninges are important for brain and skull development, but their importance extends to later in life too, where they have roles in responding to injuries and diseases like meningitis, stroke, Alzheimer’s disease and multiple sclerosis.

Addressing old questions with new methods

The meninges are clearly an important structure and, despite having been studied since the third century, our understanding of them is limited. In fact, we still don’t fully understand the types of cells that compose them and how they function. That’s where Ebert’s research comes in. She aims to close this knowledge gap by examining the cells that make up the three major meningeal layers, and how they connect to cells in the brain to create a barrier.

Using mouse models and tools called single-cell transcriptomics, Ebert can look at thousands of individual cells from the meninges and gather a detailed view of gene expression in each cell type. By isolating and analyzing individual cells, she has been able to characterize the various cell types that make up the healthy meninges in the developing and adult mouse brain, and has even identified two distinct groups of fibroblasts, one in the dura, and another in the arachnoid and pia mater.

Excitingly, Ebert has applied a new method that adds spatial information to her single-cell transcriptomic data, allowing her to investigate the layout of different cells (such as meningeal, vascular, brain and immune cells) which form the important meningeal barrier. She has also used this technique to examine how neighbouring cells in the meninges may communicate with each other.

PhD candidate Sarah Ebert smiles to camera, sitting down at an instrument in the lab.

Ebert using a cryosectioning instrument to collect thin slices of frozen brain tissue for spatial transcriptomic analysis.

Understanding the meninges in injury and repair

Given the role of the meninges in shielding the brain and responding to injury and disease, Ebert’s research has great clinical importance. With single-cell techniques and mouse models that allow her to visually tag fibroblasts, Ebert now turns her attention to determining how meningeal cells respond to their environment and mediate repair after injury.

“The advent of technologies like single-cell sequencing and spatial transcriptomics has transformed our ability to study interactions between the immune and vascular systems and the brain at an unprecedented level of detail. This shift in understanding redefines the meninges from a simple barrier to a dynamic interface, opening new avenues for investigating conditions such as multiple sclerosis, traumatic brain injury, concussions, and even brain surgery—areas where this unique tissue structure is increasingly implicated.”

Ultimately, Ebert’s work deepens our understanding of how the healthy meninges are composed and furthers our knowledge of how the barrier might be maintained. Her future research will also provide a novel and valuable insight into the meninges during injury and repair.

To hear more about Ebert’s research and her journey as a PhD candidate, check out our podcast-style interview with her below.

Interested in her research? Listen from the start. More interested in learning about her journey and advice as a PhD candidate? Skip to 8:25.