DOI: 10.6084/m9.figshare.29665121.v1
title: <b>Clara Mater: Discovery of a New Meningeal Layer in the Human CNS</b>

description: Kumar et al. (2025) proposed the existence of an intermediate leptomeningeal layer (ILL) in the human central nervous system, offering structural validation for the subarachnoid lymphatic-like membrane (SLYM) previously identified by Mollgård et al. (2023), chiefly, in mouse brains. In keeping with the tradition of assigning evocative names to meningeal layers, the authors suggested a colloquial term for this newly described structure: <i>Clara mater</i>. Here is an explainer for this discovery by the lead author of the study.<b>Mapping the Layer</b><br><i>How extensive is the ILL along the neural axis of the human CNS?</i><br>The ILL extends across the entire neural axis—from the brain’s cortex down through the brainstem and to the terminal end of the spinal cord. What’s more, it also ensheathes the cranial and spinal nerves. We demonstrated the presence of the ILL in the cortex (that’s in Video 1), in the brainstem and cerebellum (Video 3), in the spinal cord (Video 4), and even surrounding the cranial nerves, like the optic nerve (Video 5).<b>An Independent Meningeal Layer</b><br><i>Is this an independent layer like pia or arachnoid mater?</i><br>Yes, it is an independent layer. To establish it as a truly independent meningeal layer, we applied well-accepted criteria in classic anatomy textbooks. It had to be physically separable, it had to enclose CSF-filled spaces, and it had to be interconnected by trabeculae, with vessels and nerves passing through. We demonstrated all of these. On top of that, we validated the ILL-using layer-specific immunohistological markers and electron microscopy, confirming it is distinct from both pia and arachnoid mater.<b>Regional Specificity</b><br><i>Does this layer behave the same everywhere, or are there region-specific features?</i><br>There are regional peculiarities. In the cortex, for example, the ILL dips into sulci and fissures, much like the pia mater. But it goes further—it carries blood vessels within a double fold and forms unique intra-layer trabeculae that act like a seal at the entrance of sulci and fissures. In the spinal cord, the ILL becomes significantly thicker, nearly comparable to the arachnoid. Interestingly, structures like the ligamentum denticulatum, linea splendens, and filum terminale, which we used to attribute to the pia, are derived from the ILL.<b>Rethinking the Choroid Plexus</b><br><i>What about the tela choroidea and choroid plexus? Traditionally, they’ve been considered to derive from pia mater.</i><br>Our dissections showed that the tela choroidea is a double fold of the ILL that carries blood vessels into the ventricles. These vessels, along with the ILL, then associate with the ependymal lining to form the choroid plexus. The pia is closely adherent to the brain and logically cannot peel away to form such folds. But the ILL is more loosely attached, allowing it to do so. And yes, we confirmed the ILL’s contribution through immunohistochemical evidence.<b>Barrier-like Properties</b><br><i>Is the ILL impermeable and does it have barrier functions like the arachnoid mater?</i><br>Not entirely. While it does restrict molecular passage, it is not completely impermeable. For instance, a 2023 study by Mollgård et al. showed it could restrict molecules up to 1 micron in size or 3 kDa in mass. In our study, we found the ILL is non-sieved and expresses tight and adherens junction markers, just like the arachnoid barrier. So, it certainly has barrier-like properties, but further studies are needed to fully define its permeability characteristics.<b>Immune Activity</b><br><i>Does the ILL have any immune function?</i><br>Yes, and this is where things get clinically exciting. Mollgård’s group showed in mouse brains that the ILL hosts immune cells like dendritic cells and macrophages, and their presence increases with inflammation or aging. In our spinal cord samples, we observed unique macrophage-like meningothelial cells in the ILL. We confirmed this with immunohistochemistry and electron microscopy. These immune cell-like properties of the ILL hint at its possible role in immune surveillance against invading pathogens.<b>Implications for Neuroscience & Medicine</b><br><i>What could this discovery mean for neuroscience and medicine?</i><br>Including the ILL as an additional meningeal layer reshapes our understanding of CNS protection, CSF circulation, and drug delivery. It may also be critical for immune surveillance in the brain. If this layer becomes compromised—whether by trauma, infection, or inflammation—it might contribute to neurodegenerative diseases like Alzheimer’s, Parkinson’s, or multiple sclerosis. Also, because the ILL forms perivascular sheaths, it might participate in the glymphatic system, our brain’s waste clearance mechanism. So yes, this layer opens new physiological and therapeutic frontiers.<b>Nomenclature – What’s in a Name?</b><br><i>Mollgård’s group referred to it as the SLYM—Subarachnoid Lymphatic-like Membrane—whereas Kumar et al. call it the ILL and have also proposed a more poetic term: Clara mater. Is there any rationale behind these names?</i>Mollgård’s group, working primarily with mouse brains, found that this layer expressed some lymphatic markers—like Prox1 and podoplanin—but not others, such as Lyve-1 or Vegfr-3. Because of that partial expression, they coined the name SLYM, or Subarachnoid Lymphatic-like Membrane, emphasizing its immune-related features.<br>Now, our findings in human brains align with theirs in terms of cellular and molecular characteristics. But what sets our study apart is that we’ve shown, for the first time, clear macroscopic evidence of this layer—its physical presence along the entire CNS. And based on its anatomical position—intermediate within the subarachnoid space—we named it the Intermediate Leptomeningeal Layer, or ILL.<br><i>But what about Clara mater?</i>In anatomical tradition, meningeal layers have Latin-derived poetic names—dura mater (the tough mother), arachnoid mater (spider-like), and pia mater (tender mother). In keeping with that spirit, we proposed <i>Clara mater</i>, meaning “bright or clear mother,” inspired by how this layer appears gleaming and translucent in fresh postmortem dissections. So, while ILL serves as a precise scientific term, Clara mater pays homage to anatomical history and the visual beauty of this newly revealed structure.<b>Keywords:</b> Brain, CSF, Human, Intermediate layer, Leptomeninges, Subarachnoid space compartments, Spinal cord, Clara mater<b>References and further reading:</b>1. Kumar, A., Paikra, S. K., Kumar, R., Narayan, R. K., Jha, R. K., Yadav, S. S., ... & Asghar, A. (2025). Structural Validation of the Intermediate Leptomeningeal Layer in the Human Central Nervous System. <i>bioRxiv</i>, 2025-07. https://www.biorxiv.org/content/10.1101/2025.07.14.664673v12. Møllgård, K., Beinlich, F. R., Kusk, P., Miyakoshi, L. M., Delle, C., Plá, V., ... & Nedergaard, M. (2023). A mesothelium divides the subarachnoid space into functional compartments. <i>Science</i>, <i>379</i>(6627), 84-88. https://www.science.org/doi/10.1126/science.adc88103. Kumar, Ashutosh; Kumar, Rajesh; Rastogi, Ashok Kumar; Narayan, Ravi Kant; Kumar, Sanjeev; Jha, Rakesh Kumar; et al. (2025). Postmortem Dissection of the Intermediate Leptomeningeal Layer in the Human Central Nervous System. figshare. Media. https://doi.org/10.6084/m9.figshare.29375426.v24. Kumar, A., Kumar, R., Narayan, R. K., Nath, B., Datusalia, A. K., Rastogi, A. K., ... & Asghar, A. (2025). Anatomical correlates for the newly discovered meningeal layer in the existing literature: A systematic review. The Anatomical Record, 308(1), 191-210. https://anatomypubs.onlinelibrary.wiley.com/doi/10.1002/ar.25524<br>