Journal Article

Cerebrospinal fluid influx drives acute ischemic tissue swelling

Martens, Erik A., Bork, Peter A. R., Stæger, Frederik Filip, Kleinfeld, David, Hirase, Hajime, Sweeney, Amanda M., Peng, Weiguo, Mehta, Rupal I., Blinder, Pablo, Hjorth, Poul G., Toro, Edna R., Solis, Orestes, Samson, Andrew J., Bashford, Logan, Mortensen, Kristian Nygaard, Du, Ting, Nedergaard, Maiken, Mestre, Humberto, Liu, Guojun, Tithof, Jeffrey, Kelley, Douglas H., Thomas, John H., Mori, Yuki

2020

Overview

The brain is enveloped in a cushion of cerebrospinal fluid (CSF), which normally provides protection and helps to remove metabolic waste. CSF transport has also recently been shown to play unexpected roles in neurodegeneration and sleep. Mestre et al. used multimodal in vivo imaging in rodents and found that, after a stroke, an abnormally large volume of CSF rushes into the brain, causing swelling (see the Perspective by Moss and Williams). This influx of CSF is caused by constrictions of arteries triggered by a well-known propagating chemical reaction-diffusion wave called spreading depolarization. CSF transport can thus play a role in brain swelling after stroke. Science , this issue p. eaax7171 ; see also p. 1195 In rodent models, the influx of cerebrospinal fluid along the glymphatic pathway swells the brain during ischemic stroke. Stroke affects millions each year. Poststroke brain edema predicts the severity of eventual stroke damage, yet our concept of how edema develops is incomplete and treatment options remain limited. In early stages, fluid accumulation occurs owing to a net gain of ions, widely thought to enter from the vascular compartment. Here, we used magnetic resonance imaging, radiolabeled tracers, and multiphoton imaging in rodents to show instead that cerebrospinal fluid surrounding the brain enters the tissue within minutes of an ischemic insult along perivascular flow channels. This process was initiated by ischemic spreading depolarizations along with subsequent vasoconstriction, which in turn enlarged the perivascular spaces and doubled glymphatic inflow speeds. Thus, our understanding of poststroke edema needs to be revised, and these findings could provide a conceptual basis for development of alternative treatment strategies.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Animals / Aquaporin 5 - metabolism / Autopsies / Bioaccumulation / Blood flow / Blood vessels / Brain / Brain damage / Brain Edema - cerebrospinal fluid / Brain Edema - diagnostic imaging / Brain Edema - etiology / Cations / Cerebrospinal fluid / Chemical reactions / Chemistry / Constrictions / Cushions / Disease / Edema / Evaluation / Glial cells / Glymphatic System - physiopathology / Head injuries / Health services / Histology / In vivo methods and tests / Ions / Ischemia / Magnetic Resonance Imaging / Male / Medical imaging / Metabolic wastes / Metabolism / Mice / Mice, Inbred C57BL / Moisture content / Networks / Neuroglia / Occlusion / Radioisotopes / RESEARCH ARTICLE SUMMARY / Rodents / Spreading / Stroke / Stroke - cerebrospinal fluid / Stroke - complications / Stroke - diagnostic imaging / Substantia alba / Tissues / Vasoconstriction / Veins & arteries / Water content / Water inflow / Wave propagation