Year of Publication

2023

College

Arts and Sciences

Department/School/Program

Neuroscience

Degree Name

Bachelors of Science

Faculty Advisor

Adam Bachstetter

Abstract

The meninges are made up of three membranes; the pia mater, arachnoid mater, and dura mater, that surround the brain and spinal cord. These specialized layers work in concert with cerebrospinal fluid (CSF), to protect the central nervous system by adding a layer of cushion and removing waste products from the CNS. Additionally, the meninges act as a physical barrier between the central nervous system and the periphery. The meningeal lymphatic system is a specialized group of vessels that lie within the meninges that assist in the flow of fluid and waste products from the brain. If the meningeal lymphatic system malfunctions, there is a decreased ability to remove toxins from the brain, for example amyloid beta. Interleukin-1 (IL1) is a cytokine that initiates a cascade of inflammatory pathways through the interleukin-1 receptor (IL-1R1). If IL-1R1 is localized within the meninges, it may play a role in secondary injury cascades of hemorrhages, as well as in the signaling of myeloid cells from the dura mater to the brain. The goal of this study is to establish a meningeal extraction protocol and to establish whether and where IL-1R1 resides in the meninges. To do so, the skullcaps were extracted from the mice following transcardial perfusion. The mice used for this study were IL-1R1 reporter mice that have been genetically altered to express red fluorescent protein (RFP) in any cell that also expresses IL-1R1. This allows us to visualize the expression pattern in the brain. The leptomeninges were pulled from the skull cap and stained using immunohistochemistry for astrocytes using glial fibrillary acidic protein (GFAP) and lymphatic vessel endothelial receptor - 1 (LYVE-1) to label vasculature throughout the meninges. The GFAP staining did reveal astrocytes within the confluence of sinuses. While it is currently unclear why astrocytes localized to the confluence of sinuses, further work will investigate these cells in the meninges. Staining for RFP revealed that there is IL-1R1 expression within the meninges. LYVE-1 staining outlined the localization of the vasculature within the meninges. Future directions will work to determine what cell type within the meninges are expressing IL-1R1. To do so, the meninges tissue will be serial stained with GFAP, RFP, and LYVE-1.

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