Table 3.

Main neuroprotective and neuroregenerative effects of transcranial magnetic stimulation.

Model	Stroke stage	Technique	Types of protocol	Results	Neurogenesis	Neuroprotection	Neural plasticity	Neuroinflammation	Angiogenesis	Excitability	Oxidative stress	BBB	Effects	Signalling pathway	Data
Healthy animals		HF-rTMS	Progressive number of trains (15 Hz, 5 s duration, 75 stimuli) separated by 10 s intervals (one treatment was delivered on day 1, up to five on day 5)	Augmented number of thin spines and enhanced dendritic complexity			✓						Did not increase anxiety in mice	Possible BDNF and calcium-dependent signaling pathways	Cambiaghi et al., [25]
Photothrombotic stroke model	Acute	cTBS	rTMS, 1/day, 5 min, days 1-6 after stroke, 3 pulses of 50 Hz, repeated every 200 ms, magnetic field adjusted to 200 gauss	Vascular repair and protection - RECA-1, protein collagen IV with FITC-labelled dextran leakage abated by over 50% in rTMS group rats; upregulation of IGFBP1, TGFβ, VEGF, and PDGFRβ; preserved neuronal morphology and synaptic structure; reduces microgliosis and induces a shift in in microglia phenotype; suppresses proinflammatory cytokine production;		✓	✓	✓	✓		✓	✓	Protected behavioral outcomes; attenuated infarct volume; promoted functional recovery	HIF-1α pathway; antiapoptotic pathways caspase-3 and caspase-9	Zong et al., [19]; Zong et al., [20]
MCAO model		HF-rTMS	Magnetic stimulation for 3 s followed by rest for 50 s and repeated 10 times (300 pulses per day) at a rate of 10 Hz, 3.5 T peak magnetic welds; performed at 24 h, 7 and 14 days after stroke	Increased number of BrdU and NESTIN+ cells; Bcl-2 expression was significantly lower and Bax expression was significantly higher; mRNAs of BDNF and TrkB levels were also significantly higher	✓	✓							Improvement of cognitive impairment	BDNF/TrkB signaling pathway and antiapoptotic pathways Bcl-2 and Bax	Guo et al., [146]
			A 3.5 T peak magnetic weld was applied to conscious rats at day 4 after cerebral ischemia, 10 sessions of stimulation over a 2-week period, seven times of five 1 s strains at a rate of 10 Hz with a 1 s intertrain interval per day (a total of 3,500 impulses)	Greater number of positive Bcl-2 cells and fewer Bax-positive cells in the rTMS group		✓							Beneficial effect on motor function on Barnes maze performance, motor behavioral index scores, and beam balance test	Antiapoptotic pathways Bcl-2 and Bax	Yoon et al., [145]
		HF -TMS and iTBS	20 Hz rTMS and iTBS, maximum stimulator output of the magnetic stimulator of 6.0 T, 7 and 14 days	Improvement of functional recovery, reduction of the infarcted area volume, neurogenesis (KI67, DCX, NESTIN)	✓								Elevated protein levels of BDNF and phosphorylated TrkB	BDNF/TrkB signaling pathway	Luo J et al., [148]
	Acute and chronic	LF-rTMS	2 times a day, 30 pulses each time, with a frequency of 0.5 Hz and magnetic field intensity of 1.33 tesla, when the animals were awake after MCAO, for 1, 7, 14, 21, and 28 days	Higher c-FOS expression, higher BDNF expression in 7, 14, and 21 days after stroke groups			✓						Improved functional outcome	BDNF/TrkB signaling pathway	Zhang et al., [26]
		LF-TMS and peripheral nerve stimulation	Paired associative stimulation with a frequency of 0.05 Hz 90 times over 4 weeks (TMS and left tibial nerve stimulation, 1/day); the interpair and interstimulus intervals were 20 seconds and 15 ms, respectively; 7, 14, and 28 days	Higher average BDNF and NMDAR1 expression levels		✓	✓			✓			Learning and memory amelioration, neuroplastic effect	BDNF/TrkB signaling pathway	Hu et al., [149, 150]

MCAO: middle cerebral artery occlusion; HF-rTMS: high-frequency repetitive transcranial magnetic stimulation; rTMS: repetitive transcranial magnetic stimulation; LF-rTMS: low-frequency repetitive transcranial magnetic stimulation; FITC: fluorescein isothiocyanate; IGFBP1: insulin-like growth factor binding protein 1; TGFβ: transforming growth factor β; VEGF: vascular endothelial growth factor; PDGFRβ: platelet-derived grow factor receptor beta; HIF-1α: hypoxia-inducible factor 1α; BDNF: brain-derived neurotrophic factor; TrkB: tropomyosin receptor kinase B; iTBS: intermittent theta burst stimulation; cTBS: continuous theta burst stimulation; NMDAR1: N-methyl-D-aspartate receptor 1.