{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:53:19Z","timestamp":1791363199065,"version":"4.3.1"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Deep brain stimulation (DBS) is an established symptomatic therapy for Parkinson\u2019s disease (PD), yet its biological effects extend beyond modulation of abnormal basal ganglia circuitry. This review conceptualizes DBS in PD as a neuroimmune-metabolic intervention acting across the electrode-tissue interface, glial networks, peripheral immunity, and activity-dependent metabolic systems. PD is characterized by convergent immune and metabolic vulnerability. These processes create a disease environment in which electrical stimulation may interact with inflammation, excitotoxicity, bioenergetic stress, and neuronal resilience. We distinguish implantation-related tissue responses from stimulation-induced biological remodeling. Electrode insertion produces acute injury, blood-brain barrier (BBB) disruption, peri-electrode edema, gliosis, and foreign-body responses, which should not be conflated with the effects of chronic stimulation. Active DBS may modulate central cytokine expression, microglial and astrocytic phenotypes, inflammasome activity, astrocytic glutamate transport, and brain-peripheral immune crosstalk. Emerging evidence also suggests a neurometabolic dimension, including changes in regional glucose utilization, PD-related metabolic network expression, oxidative stress, and neurotrophic signaling. However, these effects are context-dependent and influenced by multiple factors. Although preclinical studies support potential neuroprotective mechanisms involving BDNF\/TrkB signaling, mitophagy, reduced excitotoxic-inflammatory coupling, and immune-metabolic rebalancing, clinical evidence remains insufficient to establish DBS as a disease-modifying therapy. Future studies should integrate multiple methods such as longitudinal imaging, electrophysiology, immune profiling and metabolomics. DBS should be understood as a symptomatic circuit-based therapy that may also interact with neuroimmune and metabolic processes, while current evidence remains insufficient to establish a disease-modifying role in PD.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1940474","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T08:35:21Z","timestamp":1791362121000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Deep brain stimulation as neuroimmune-metabolic modulation in Parkinson\u2019s disease and beyond: tissue response, glial remodeling, and disease modification"],"prefix":"10.3389","volume":"17","author":[{"given":"Hao","family":"Deng","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Gaoxin Hospital Affiliated to West China Second School of Medicine, Sichuan University","place":["Chengdu, Sichuan, 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