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. 2023 Jul 6;15:1173987. doi: 10.3389/fnagi.2023.1173987

Table 2.

Neuroinflammation modulation by VNS in animal model.

Authors Year Models VNS setting Physiology/function studied
Mihaylova et al. 2012 Rat 2 mA, 2 Hz, pulse width 0.3 ms, 10 min, repeated every 45 min, total 4.5 h Anti-inflammatory effect of VNS on cerebral microcirculatory integrity
Meneses et al. 2016 Rat 0.75 mA, 5 Hz, pulse width 2 ms, 30 s Anti-inflammatory effects of VNS
Farrand et al. 2017 Rat 0.8 mA, 30 Hz, 100 μs, 500 ms, 15 biphasic pulses every 30 s, 30 min twice, 4 h apart, 10 days Therapeutic potential of VNS in a rat PD model
Nizamutdinov et al. 2018 Rat Amplitude n/a, 5 Hz, pulse width 1 ms, 30 s on, 4 min and 30 s off, for 2 or 4 weeks Pain threshold restoration by VNS in a GWI rat model
Jiang et al. 2018 Rat Percutaneous auricular VNS: 0.8 mA, 30 Hz, 500 ms train of 15 biphasic pulses every 30 s, 30 min, every 2 days for 8 days, acupuncture needles inserted into the left cavum concha SN dopaminergic neurodegeneration, the associated neuroinflammation and immune responses in PD animals
Chen et al. 2018 Mice 0.5 mA, 5 Hz, 30 s every 5 min for 1 h Effects on CMI by VNS in animals of CMI when exposed to colitis and the anti-inflammatory mechanisms
Huffman et al. 2019 Mice Percutaneous cervical VNS: amplitude to reach 10% reduction in HR, 20 Hz, pulse width 300 ms, biphasic, charge-balanced pulses, 30 min, echo-guided needle electrode insertion at carotid sheath Change of microglial activation and cognitive dysfunction following LPS endotoxinemia by VNS
Cai et al. 2019 Rat Percutaneous auricular VNS: 0.5 mA, 20 Hz, 30 s train, 4 times, 5 min apart, acupuncture needles implanted on the left cavum concha Changes of surgery-induced cognitive dysfunction in an aged rat model of POCD by VNS
Farrand et al. 2020 Rat 0.75 A, pulse width 250 μs, with (1) low VNS: 10 Hz, 30 min on, 23.5 h off (2) standard VNS: 20 Hz, 30 s on, 5 min off, 24 h/day (3) burst VNS: 300 Hz (10 pulses per burst), 19 s inter-burst interval, 24 h/day Different VNS paradigms in a PD animal model
Guo et al. 2020 Rat Transauricular VNS (taVNS): 2 mA, 15 Hz, 30 min, 28 days, self-adsorption conductive magnet fixed in bilateral cavity of the auricular concha Anti-inflammatory effect of VNS in rats with depression and chronic somatic pain comorbidity
Zhang et al. 2020 Rat 1 V, 5 Hz, 2 ms, 30 s on, 5 min off, for 20 min Changes of neuroinflammation and CIPN by VNS via CAP
Venkatasamy et al. 2021 Mice Amplitude n.p., 5 Hz, pulse width 1 ms, 30 s on, 4 min 30 s off, continuous for 2 weeks Chronic cognitive deficit and hippocampal astrocytosis in a rat model of GWI
Wang J. Y. et al. 2021 Rat Percutaneous auricular VNS: EA apparatus at the auricular concha, 2 mA, 2 and 15 Hz, switched every s, 30 min/days, 21 days Changes of hippocampal neuroinflammation and role of α7nAChR by taVNS
Liu et al. 2022 Rat Transcutaneous cervical VNS on skin covering right vagal nerve, 3 parameters tested: (1) voltage: 1 V, 11.4 V, or 24.4 V, 25 Hz, 2 min (2) duration: 11.4 V, 25 Hz, 2 or 3 rounds of 2 min, 5 min apart, or single 6 min (3) chronic daily VNS: 11.4 V, 25 Hz, 2 rounds of 2 min, 5 min apart, 4 weeks vs. single VNS Optimal nVNS paradigm for migraine
Namgung et al. 2022 Rat Acute VNS: 10 mA, 5 Hz, pulse width 5 ms, 5 min Chronic VNS: 10 mA, 5 Hz, pulse width 5 ms, 5 min, 7 days Regulation of pro-inflammatory cytokines in the hippocampus in a rat model of continuous stress
Tang et al. 2022 Rat 0.5 mA, 20 Hz, pulse width 0.5 ms, 30 s on and 5 min off, total 1h Neuroprotective effects of VNS through α7nAChR-mediated inhibition of pyroptosis
Iannucci et al. 2022 Mice Amplitude n/a, 5 Hz, 1 ms pulse width, 30 s on, 4 min 30 s off, total 2–4 weeks Improvement of cognitive impairment and hippocampal dysfunction by VNS in a model of GWI
Chen et al. 2022 Rat 1.0 mA, 0.5 ms, 30 Hz, 10 min/day, 14 days Efficacy and therapeutic mechanism of VNS in SCI
Caravaca et al. 2022 Mice 1 mA, 250 μs biphasic pulse, 50 s interphase delay, 10 Hz, 5 min Resolution of inflammation by VNS

α7nAChR, α7 nicotinic acetylcholine receptor; CAP, cholinergic anti-inflammatory pathway; CIPN, chemotherapy-induced peripheral neuropathy; CMI, cerebral cortical microinfarct; EA, electroacupuncture; GWI, Gulf War Illness; LPS, lipopolysaccharide; n/a: not applicable; PD, Parkinson's disease; POCD, Post-operative cognition decline; SCI, spinal cord injury; SN, substantia nigra; VNS, vagus nerve stimulation.