Table 2.

Experimental models of neuroprotection by limb RIC: limb RIC targets autonomous nervous system and affects circulating blood factors, exosomes and blood cells

Model	Pathway/mechanism	Reference
Rat: Sprague–Dawley (m/250–350 g) IS model: BCCAO 30 min, perm. MCAO pre-RIC: immediately before IS 3 cycles: 15 min RIC + 15 min RF	galectin-9/Tim-3 inflammatory cell signaling pathway, NO, iNOS, BBB, afferent nerves	[78]
Rat: Wistar (m/250-320 g) IS model: global 4-VO + BCCAO 8 min pre-RIC: before IS 3 cycles: 10 min RIC + 10 min RF	hippocampus CA1, serum, NO/NOS	[77]
Rat: Sprague–Dawley (m/240–250 g) IS model: MCAO 90 min per-RIC: 30 min before reperfusion 3 cycles: 5 min RIC + 5 min RF	platelet-derived microparticles	[83]
Rat: Sprague–Dawley (m/280–320 g) IS model: 1.5 h MCAO + 24 h RF per-RIC/post-RIC (I-30, RF-30) 3 cycles: 10 min RIC + 10 min RF	No neural transmission in per-RIC	[84]
Rat: Sprague–Dawley (m/280-320 g) IS model: 1.5 h MCAO, 3d RF pre-RIC: 1 h before MCAO 4 cycles: 5 min RIC + 4 min RF	TNFα, IL-6, IL-10; Lymphocytes: Tc, Th, NKT, B, NK; monocytes	[85]
Rat: Sprague–Dawley (m/age NA) IS model: MCAO (90 min w/isoflurane) pre-RIC: before IS 4 cycles: 5 min RIC + 4 min RF	spleen, T lym, Tc, NKT, B-lym, RIC immune response is dependent on the spleen	[86]
Mouse: type 2 diabetic BKS.Cg-Dock7m + / + Leprdb/Nju, db/db (m/8wo) IS model: 45 min MCAO + 48 h RF pre-/post-RIC: 1d before MCA/after RF 3 cycles: 10 min RIC + 10 min RF	Lymphocytes: Th, Tc, NK, B, pERK, pAKT, TNF-α, IL-6, IL-1β, IFN-γ, IL-4	[76]
Mouse: C57BL/6 (m/8–10 wo) IS model: 70 min MCAO, 24 h RF per-RIC: during MCAO 3 cycles: 10 min RIC + 10 min RF	erythrocytes oxygen delivery 2,3-biphosphoglycerate	[87]
Mouse: C57BL/6, CCR2 KO (m/f, 12wo) IS model: 30 min MCAO post-RIC: 2 h after MCAO, 2d RF 5 cycles: 5 min RIC + 5 min RF RIC only: single, 3 × daily, 7 × daily	monocytes: splenic, anti-inflam., pro-inflam.; resident microglia	[88]
Mouse: C57BL/6 (m/20-22 g) IS model: 45 min MCAO post-RIC: after MCAO, 2d RF 3 cycles: 10 min RIC + 10 min RF	Lymphocytes: B, Th, Tc, NK, NKT cells, non-inflam. monocytes, IL-10, IL-6, TNF-α, IL-4, IL-1β	[79]
Cell model: HUVEC cells, SH-SY5Y cells Rat: Sprague–Dawley (m/f, 220-250 g) IS model: 2 h MCAO, 24 h RF post-RIC: after MCAO, 3 × femoral artery	CD63, HSP70 and TSG101 in plasma, exosomes (endothelial)	[89]
Human & Mouse pre-RIC 4 cycles: 5 min RIC + 5 min RF	miR-144	[90]
Rat: Wistar (m/8 wo) IS model: permanent MI post-RIC: (4w after MI), daily for 4w 5 cycles: 5 min RIC + 5 min RF	msiR-29a	[91]
Mouse: C57BL/6 (20-22 g) IS model: dMCAO electrocoagulation pre-RIC: 24 h before MCAO 3 cycles: 10 min RIC + 10 min RF	Exosomes, HIF-1α, CD63, TSG101, CD81	[92]
Mouse: C57BL6: (sex NA/8–10 wo) IS model: MCAO (1 h) pre-RIC: (1 h before MCAO) 4 cycles: 10 min RIC + 10 min RF	miR-144, p-PTEN, pAkt, apoptosis	[93]
Human: (n = 4) male/young RIC: non-dominant arm cuff 200 mmHg 5 cycles: 5 min RIC + 5 min RF Cell model: SH-SY5Y cells	plasma exosomes, miR-126, DNMT3B, DNA methylation, cell cycle, p21 (CDKN1A)	[94]