Deep brain stimulation as neuroimmune-metabolic modulation in Parkinson’s disease and beyond: tissue response, glial remodeling, and disease modification
5 affiliations
- 1Department of Neurosurgery, Gaoxin Hospital Affiliated to West China Second School of Medicine, Sichuan University
- 2Department of Emergency Medicine, West China Hospital, Sichuan University
- 3Southwest Medical University
- 4Department of Neurosurgery, West China Hospital, Sichuan University
- 5Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University
Abstract
Deep brain stimulation (DBS) is an established symptomatic therapy for Parkinson’s 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.
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BibTeX
@article{deng2026deep,
title = {{Deep brain stimulation as neuroimmune-metabolic modulation in Parkinson’s disease and beyond: tissue response, glial remodeling, and disease modification}},
author = {Hao Deng and Xiaolong Li and Dihu Wang and Youheng Peng and Maoyu Wang and Hao Liang and Yang Wu and Linglong Xiao and Wei Pan and Wei Wang and Senlin Yin},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1940474},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940474/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Deep brain stimulation as neuroimmune-metabolic modulation in Parkinson’s disease and beyond: tissue response, glial remodeling, and disease modification
AU - Hao Deng
AU - Xiaolong Li
AU - Dihu Wang
AU - Youheng Peng
AU - Maoyu Wang
AU - Hao Liang
AU - Yang Wu
AU - Linglong Xiao
AU - Wei Pan
AU - Wei Wang
AU - Senlin Yin
PY - 2026
DA - 2026/10/07
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1940474
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1940474/full
AB - Deep brain stimulation (DBS) is an established symptomatic therapy for Parkinson’s 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.
SN - 1664-3224
ER -