Scientists image brain drainage in mice and humans

Meningeal lymphatic vessels (MLVs) are located in the dura mater of the brain and spinal cord of various vertebrate species, including humans. They ensure waste product elimination and immune surveillance of brain tissues. Whether MLVs exist in the anterior part of the murine and human skull and how they connect with the glymphatic system and extracranial lymphatics remained unclear.

Scientists at Yale and the Paris Brain Institute (Pitié-Salpêtrière Hospital, Paris) used light-sheet fluorescence microscopy to image brain drainage by meningeal lymphatics in mice and humans. They demonstrate that CSF drainage pathways are similar between mice and humans. The study reports a novel MRI-based imaging technique for patients with neurological diseases.

The lymphatic vascular system monitors immune surveillance and waste elimination within tissues and organs. Lymphatic vessels are absent from the central nervous system (CNS) but present at the CNS borders, in the meninges that protect the brain and the spinal cord.

Laurent Jacob, Ph.D., first author of the study and a member of the Paris research team, said, “The meningeal lymphatic system affects neurological diseases in many mouse models, including Alzheimer’s disease, multiple sclerosis, brain tumors, and other conditions. Because of its involvement in many diseases, the meningeal lymphatic system has attracted much therapeutic interest.”

“However, it remained unclear where the lymphatic recapture of CSF molecules occurs in the context of the whole head, in mice or humans.”

Scientists wanted to learn more about the architecture and function of the meningeal lymphatic network. They investigated CSF lymphatic drainage using postmortem light-sheet imaging in mice and real-time magnetic resonance imaging in humans. The combination of these approaches allows scientists to rebuild the entire lymphatic drainage network of the CSF.

The meningeal lymphatics contact the dura mater’s venous sinuses, and the 3D imaging revealed a vast meningeal lymphatic network around the cavernous sinus in the anterior part of the skull. Meningeal lymphatics drain into cervical lymph nodes after leaving the skull through cranial foramina.

Stéphanie Lenck, MD, also at the Pitié-Salpêtrière Hospital, performed quantitative lymphatic MRI on 11 patients affected by various neurological diseases. She established a procedure for 3D visualization of all blood and lymphatic vasculature in the meninges and the neck that revealed a significantly greater meningeal lymphatic volume in men than in women.

In the future, scientists are planning to explore whether this anatomical data is causally related to the greater predisposition of women to develop neurological diseases such as multiple sclerosis, meningiomas, or intracranial hypertension.

Journal Reference:

1. Laurent Jacob, Jose de Brito Neto et al. Conserved meningeal lymphatic drainage circuits in mice and humans. J Exp Med (2022) 219 (8): e20220035. DOI: 10.1084/jem.20220035