Modulating Cerebrospinal Fluid Composition in Neurodegenerative Processes: Modern Drug Delivery and Clearance Strategies

Neurodegenerative diseases, traumatic brain injuries, and strokes are accompanied by the development of secondary damage—a long-term pathological cascade in which cerebrospinal fluid (CSF) plays a key role. Unlike primary damage, which is acute, secondary processes can progress over months and even years, creating a therapeutic window for neuroprotection. CSF acts not simply as a passive medium but as an active mediator of the spread of cytotoxic factors—reactive oxygen species, glutamate, proinflammatory cytokines, pathological protein aggregates (Aβ, α-synuclein, tau, etc.), and exosomes—which transport toxic molecules between brain regions. These processes are exacerbated by dysfunction of the blood-brain and blood–cerebrospinal fluid barriers, leading to the accumulation of damaging agents in the CSF and accelerated neurodegeneration. This review examines the molecular mechanisms of secondary injury, the role of barrier systems in maintaining CSF homeostasis, and current therapeutic strategies aimed at modulating CSF composition. Particular attention is paid to innovative approaches to drug delivery to the central nervous system—from bispecific antibodies and nanoparticles to invasive techniques such as immunoselective CSF aspiration and nanoporous implants. The potential of CSF as a source of diagnostic biomarkers and as a therapeutic target for personalized treatment of neurodegenerative conditions is highlighted.