Table 2.

Studies to increase Treg cells frequency and function as therapeutic approaches in IS.

Study	Treg expansion	Model	Treatment time point	Treatment duration	Effects
Li et al. [29]	Adoptive transfer	Mice: 60 min tMCAO	2, 6, or 24 h after reperfusion	Tail vein injection once	Reduced brain damage, prolonged protection, and improved functional outcomes
		Rats: 120 min tMCAO	2, 6, or 24 h after reperfusion	Tail vein injection once	Decreased infarct size, and improved functional performance
Na et al. [41]	CD28 superagonist	Mice: pMCAO	3 or 6 h after pMCAO	Intraperitoneal administration once	Reduced infarct size and attenuated functional deficit 7 days after IS
		Mice: 60 min tMCAO	3 h after tMCAO	Intraperitoneal administration once	Reduced infarct size and attenuated functional deficit 7 days after IS
Xie et al. [107]	Rapamycin (mTOR inhibitor)	Rats: 90 min tMCAO	6 h after tMCAO	Intracerebroventricular infusion with an osmotic minipump to the left lateral ventricle 7 days for neurological behavioral tests and lesion volume measurement; 3 days for studying the neuroinflammatory response	Decreased lesion volumes, reduced production of proinflammatory cytokines and chemokines, and improved behavioral deficits
Gee et al. [117]	“Mucosal immunization” by Myelin basic protein	Rats: 3 h tMCAO	9, 7, 5, 3, 1 days before tMCAO	Instilled into each nostril every other day for a total of 5 doses	Lower neurological scores (better), induced response of Treg cells, and less likely of autoimmune response
Ishibashi et al. [115]	“Mucosal immunization” by Recombinant human E-selectin	Rats: pMCAO	32, 30, 28, 26, 24, 12, 10, 8, 6, 4 days before tMCAO	Instilled into each nostril every other day for 10 days, and repeated once after 11 days for a total of 10 doses	Decreased infarct volumes, enhanced survival of neural progenitor cells and neurons, and improved functional performance