Exp Neurobiol.  2019 Feb;28(1):104-118. 10.5607/en.2019.28.1.104.

Persistent Malfunction of Glymphatic and Meningeal Lymphatic Drainage in a Mouse Model of Subarachnoid Hemorrhage

• Pu T
• Zou W
• Feng W
• Zhang Y
• Wang L
• Wang H
• Xiao M

• KMID: 2439010
• DOI: http://doi.org/10.5607/en.2019.28.1.104

Abstract

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3⁺, CD4⁺, and CD8⁺ cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.

Keyword

Subarachnoid hemorrhage; Dural lymphatics; Glymphatic system; Aquaporin 4; Fluorescent tracers

MeSH Terms

Animals
Apoptosis
Aquaporin 4
Astrocytes
Brain
Brain Ischemia
Cisterna Magna
Drainage*
Edema
Hippocampus
Lymph Nodes
Mice*
Neuroglia
Neurons
Prognosis
Spasm
Subarachnoid Hemorrhage*
tau Proteins
Aquaporin 4
tau Proteins