Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering

Neurosurgical diseases-including brain tumors, hemorrhage/trauma, ischemia, infection, epilepsy, and spinal cord injury-share convergent neuro-immune mechanisms. In the acute phase, sterile inflammation and barrier disruption trigger innate immune cascades. During the subacute phase, immune resolution and clearance determine the quality of tissue repair. In the chronic phase, persistent immune-glia interactions and synaptic remodeling influence epileptogenesis and long-term cognitive outcomes. Recent discoveries-such as the meningeal immune niche, meningeal lymphatic system, and glymphatic clearance pathways-have redefined the classical concept of "CNS immune privilege." The central nervous system is no longer viewed as immune-isolated, but rather as a compartment whose immunity can be directly modulated by surgical intervention and perioperative management. This review proposes a conceptual framework in which neurosurgery serves as a programmable "immune anchor point." By integrating knowledge of neuro-immune interface architecture and temporal dynamics, we establish a closed-loop model encompassing structural pathways, immune dynamics, delivery/timing, and efficacy/toxicity. This paradigm shift aims to accelerate breakthroughs in CNS immunotherapies. The article unfolds along three main themes: (1) the structural foundations of neuro-immune communication-including barrier systems, the meningeal immune niche, and meningeal lymphatic-glymphatic coupling; (2) temporal immune dynamics across acute, subacute, and chronic phases, and their roles in edema, secondary injury, and failed resolution; and (3) the brain tumor immune microenvironment, with a focus on surgical synergy and analysis of why immunotherapies (checkpoint inhibitors, vaccines, oncolytic viruses, cell therapies) have largely failed in glioblastoma. Finally, we propose a translational roadmap integrating perioperative immune management, spatial omics stratification, and local immunoengineering.