Table 1.

In vivo studies on neuromodulation therapy regulate inflammation.

Type of Neuromodulation	Disease/model	Treatment targets	Effects on inflammation	references
TMS	Patients with refractory depression	Left dorsolateral prefrontal cortex	Decrease serum IL-1β and TNF-α	Zhao et al. [87]
	MDD patients	Bilateral DLPFC	No significant difference	Chou et al. [88]
	CUMS rat model	Vertex of the skull	Decrease hippocampus TNF-α, iNOS, IL-1β, and IL-6	Tian et al. [24]
TES	Bipolar depression patients MDD patients AD patients	DLPFC Anodal on left DLPFC and Cathodal on right DLPFC Bitemporal lobes(40 Hz tACS)	Decrease plasma IL-6 and IL-8 No significant difference Decrease of microglia activation	Goerigk et al. [21] Brunoni et al. (2014), Brunoni et al. [98] Dhaynaut et al. [100]
	Rats model of vascular dementia Healthy mice MCAO mouse model	2.5 mm posterior to bregma AP + 0.5 mm and ML + 1.5 mm from bregma(anodal tDCS) Ischemic hemispheres	Decrease hippocampal IL-1β, IL-6, and TNF-α reduce Iba1-positive microglia Increase the number of iNOS-positive M1-polarized microglia	Guo et al. [94] Pikhovych et al. [95] Braun et al. [96]
ECT	Resistant major depression patients	Right unilateral and bilateral ECT	Activate peripheral blood mononuclear cells, increases circulating IL-1β, IL-6	Fluitman et al. [108], Lehtimäki et al. [109]
	CUMS rat model	Bilateral ear clip	Increase hippocampal IL-1β and TNF-α	Zhu et al. (2015)
	Depression patients	Bitemporal	Decrease in IL-6 levels	Belge et al. (2020)
	Autoimmune encephalomyelitis	Ear clip	Reduce microglia activation, T cell stimulatory and chemokine expression	Goldfarb et al. [105]
Photobiomodulation	Aged rats	Cerebral cortex	Increase hippocampus IL-1α and decrease IL-5 and IL-8	Cardoso et al. [117]
TUS	MCAO mouse model LPS-treated mice PD mouse model	Ischemic hemispheres 2 mm posterior to the bregma STN	Increase IL-10、IL-10R and M2 microglia Inhibit activation of TLR4/NF-κB inflammatory signals and reduced TNF-α, IL-1β, and IL-6 Nnormalize the expression NF-κB, TNF-α, IL-1β and COX-2 and NF-κB	Wang et al. [93] Chen et al. [122] Zhou et al. [124]
DBS	Rats	Infralimbic cortex	Increase expression of glial fibrillary-acidic-protein, TNF-α, and p11	Perez-Caballero et al. [135]
	Rats	Subthalamic nucleus	Increase the density of PBR	Hirshler et al. (2010)
	FPI rat model	Lateral cerebellar nucleus	Suppress expression of pro-inflammatory genes, suppress microglial, and astrocytic activation	Chan et al. [136]
	Pilocarpine-induced SE rat model	Anterior thalamic nucleus	Countered the increase in hippocampal caspase3 activity and IL-6 levels, but had no effect on TNFα	Covolan et al. (2014)
	6-hydroxydopamine injection Rat PD model	Subthalamic nucleus	Suppress microglia activation and NF-κB expression, decrease IL-1β and IL-6, increase IL-4, downregulate IL-1R, ERK, and cleaved-caspase3	Chen et al. [138]
VNS	Migraineurs	Cervical vagus nerve	Decrease serum IL-1βdecrease in IL-8	Chaudhry et al. (2019)
	LPS endotoxemia in rats	Peripheral vagus nerve	Inhibit TNF synthesis, attenuate peak serum TNF amounts	Borovikova et al. [139]
	LPS endotoxemia in mice	Vagus nerve	Reduce the central levels of IL-1β, IL-6, and TNFα, prevent LPS-induced hippocampal microglial activation	Huffman et al. (2019) Meneses et al. [140]
	POCD-aged rat model	Auricular vagus nerve	Decrease hippocampus TNF-α, IL-1β, and the expression of NF-κB suppress the elevated level of TNF-α	Cai et al. (2019)
	CUMS and CCI rat model	Transcutaneous auricular vagus nerve	Decrease plasma and multiple brain regions TNF-α	Guo et al. [94]

CUMS chronic unpredictable mild stress, STN subthalamic nucleus, MCAO middle cerebral artery occlusion, PBR peripheral benzodiazepine receptors, reflects microglia cell density, SE status epilepticus, ERK extracellular signal-regulated kinase, LPS lipopolysaccharide, TBI traumatic brain injury, POCD postoperative cognitive dysfunction, CCI chronic constriction injury of the sciatic nerve.