The glymphatic system for neurosurgeons: a scoping review

Abstract

The discovery of the glymphatic system has revolutionized our understanding of cerebrospinal fluid (CSF) circulation and interstitial waste clearance in the brain. This scoping review aims to synthesize the current literature on the glymphatic system's role in neurosurgical conditions and its potential as a therapeutic target. We conducted a comprehensive search in PubMed and Scopus databases for studies published between January 1, 2012, and October 31, 2023. Studies were selected based on their relevance to neurosurgical conditions and glymphatic function, with both animal and human studies included. Data extraction focused on the methods for quantifying glymphatic function and the main results. A total of 67 articles were included, covering conditions such as idiopathic normal pressure hydrocephalus (iNPH), idiopathic intracranial hypertension (IIH), subarachnoid hemorrhage (SAH), stroke, intracranial tumors, and traumatic brain injury (TBI). Significant glymphatic dysregulation was noted in iNPH and IIH, with evidence of impaired CSF dynamics and delayed clearance. SAH studies indicated glymphatic dysfunction with the potential therapeutic effects of nimodipine and tissue plasminogen activator. In stroke, alterations in glymphatic activity correlated with the extent of edema and neurological recovery. TBI studies highlighted the role of the glymphatic system in post-injury cognitive outcomes. Results indicate that the regulation of aquaporin-4 (AQP4) channels is a critical target for therapeutic intervention. The glymphatic system plays a critical role in the pathophysiology of various neurosurgical conditions, influencing brain edema and CSF dynamics. Targeting the regulation of AQP4 channels presents as a significant therapeutic strategy. Although promising, the translation of these findings into clinical practice requires further human studies. Future research should focus on establishing non-invasive biomarkers for glymphatic function and exploring the long-term effects of glymphatic dysfunction.

Keywords: Aquaporin-4; Brain tumors; Glymphatic system; Head injuries; Hydrocephalus; Neurosurgery.

Fig. 1

Flow chart of study inclusion

Fig. 2

Overview of glymphatic system dysfunction in various neurosurgical conditions. This figure illustrates the involvement of the glymphatic system, which is responsible for waste clearance in the central nervous system, in several neurosurgical diseases. Each panel displays a computed tomography (CT) scan depicting a different pathological condition, accompanied by bullet points summarizing the associated changes in glymphatic function. In the center of the figure is a schematic representation of the glymphatic pathway, highlighting peri-arterial cerebrospinal fluid influx, interstitial solute movement, and solute drainage mechanisms. AQP4, aquaporin-4; CSF, cerebrospinal fluid; NPH, normal pressure hydrocephalus