Review of research advances in the cerebral lymphatic system and neurological disorders

The identification of the central lymphatic system represents a significant advancement in contemporary neuroscientific research. As a vital conduit connecting the central nervous system to the peripheral lymphatic network, the primary components of the central lymphatic system, the glymphatic system and meningeal lymphatic vessels, maintain homeostasis within the central microenvironment through cerebrospinal fluid circulation, metabolic waste clearance, and immune cell trafficking. Recent studies affirm that structural and functional perturbations within the central lymphatic apparatus can lead to the accrual of neurotoxic proteins such as amyloid-β and tau, thereby contributing to the pathogenesis of neurodegenerative conditions like Alzheimer's and Parkinson's diseases. Additionally, in cerebrovascular pathology, impaired drainage mechanisms exacerbate blood-brain barrier disruption and cerebral edema, thereby impairing neurological recovery. Moreover, this system modulates immune cell infiltration and plays a pivotal role in the etiology and progression of multiple sclerosis, central nervous system infections, and intracranial neoplasms.

This review aimed to systematically synthesize the core components of the cerebral lymphatic system, namely the glymphatic system and meningeal lymphatic vessels, and clearly outline the key influencing factors, including aquaporin-4 activity, aging, hemodynamics, sleep, and circadian rhythms. The study aimed to emphasize the mechanisms by which the cerebral lymphatic system influences neurological pathology and summarize emerging therapeutic avenues targeting lymphatic pathways within the central nervous system.

Evidence suggests that the targeted modulation of the cerebral lymphatic system has the potential to treat various neurological diseases. Nevertheless, our understanding of the molecular mechanisms remains in its early stages, with significant research gaps. Consequently, future investigations should focus on molecular characterization to identify specific therapeutic targets, thereby facilitating the translation of preclinical insights into clinical practice.