Insights into the Role of the Glymphatic System in the Pathogenesis of Post-hemorrhagic Hydrocephalus

Abstract

Recently, it has been well-established that the glymphatic or glial-lymphatic system plays a vital role in the pathophysiology of various neurological compromise, especially hydrocephalus (HCP). Till now, the complete pathway is not yet fully understood, and little evidence is available from the literature that links hydrocephalus to disorders of the glymphatic system. Most published molecular studies and animal research have shown that, in models with hydrocephalus, the drainage of cerebrospinal fluid (CSF) via the glymphatic system is disrupted. This is strongly observed in normal pressure and post-hemorrhagic hydrocephalus cases. A thorough search of the literature to date yields scarce evidence on studies conducted on humans. Despite major similarities between non-human and human glymphatic pathways, the need for studies conducted on humans is becoming more urgent as the glymphatic pathway has been shown to be a good candidate for therapeutic intervention. In this review, we collect and report the most updated evidence addressing the glymphatic drainage pathways and their associations with the development of various types of hydrocephalus. In addition, we reveal the current scientific gap in human studies and our recommendations for the conduction of future clinical studies.

Keywords: Cerebrospinal fluid; Glymphatic system; Hydrocephalus.