Research on pathways of cerebrospinal fluid (CSF) clearance and drainage is an emerging subject, and many details remain to be elucidated. Recently, it has been shown that the dynamics of CSF outflow alters during the inflammatory and pathological stages of diseases such as glioma, and clearance from the spinal cord to the lymphatic vessels has been proposed to have significance in various diseases. However, the alterations of the CSF flow and their consequences after ischemic stroke, remain unexplored.

To explore the alterations of CSF dynamics after stroke, we use an intraluminal transient middle cerebral artery occlusion (tMCAO) model in which the base of the middle cerebral artery (MCA) is occluded for 60 minutes. After 24 hours of reperfusion, PEGylated 40kDa near-infrared (NIR) tracer (P40D800) is injected into the cisterna magna (2.5μl, 1μl/min, i.c.m). Using dynamic in vivo NIR imaging, CSF tracer efflux into the superficial (scLNs) and deep cervical lymph nodes (dcLNs), CSF flow to the thoracic and sacral spine, and, finally, overall tracer efflux into the blood circulation are quantified from the saphenous vein.

Using dynamic in vivo imaging with near-infrared CSF tracers in novel reporter mice that allow the visualization of blood and lymphatic vessels, we have quantified the CSF tracer flow and accumulation to the main drainage pathways, including the superficial and deeper cervical lymph nodes, the thoracic and sacral spine, and the clearance to the systemic circulation. We found that CSF circulation and drainage are significantly impaired within the subarachnoid space surrounding the brain and spinal cord and to the lymphatics after stroke.

Unraveling the CSF outflow dynamics after ischemia allows for a deeper understanding of the disease and may be of great value as a new diagnostic and therapeutic target for stroke patients. Impaired CSF efflux from the subarachnoid space to the cervical lymph nodes after ischemic stroke might result from edema and high intracranial pressure (ICP). High ICP and impaired CSF clearance from the brain may lead to the accumulation of toxic metabolites and further damage to the brain. Thus, alleviation of intracranial pressure after stroke by stimulating CSF outflow might improve post-stroke recovery and prevent damage to the brain.