Table 1.

Potential therapies targeting lymphatic drainage systems

Target	Mechanism	Representative drugs	Effect	Reference
Glymphatic system: AQP4	Inhibits AQP4 mediated water transport	Acetazolamide	Reduces the brain water content and improves pathology caused by infarction changes	Hao et al., 2022
		TGN-020	Reduces brain edema and infarcted volume, improves motor performance, reduces albumin extravasation, gliosis, and apoptotic cells	Igarashi et al., 2011; Pirici et al., 2017
		AER-270	Controls cerebral edema and improves neurological outcome	Farr et al., 2019
	Downregulates AQP4 expression	miR-29b	Reduces infarct volume and edema formation, attenuates blood-brain barrier disruption	Wang et al., 2015
		Methylene blue	Ameliorates brain edema, astrocytic swelling, and pathological changes of ischemia	Shi et al., 2021
		Trifluoperazine	Reduces total brain water content during the acute phase of stroke	Sylvain et al., 2021
	Promotes AQP4 repolarization	Digoxin	Attenuates brain injury and cognitive dysfunction after cerebral hypoperfusion	Cao et al., 2022
IPAD pathway: SMC	Promotes arterial dilatation and modulates SMC function	Cilostazol	Facilitates Aβ drainage along the IPAD pathway, reduces Aβ accumulation in the brain	Maki et al., 2014
		Fasudil hydrochloride	Increases IPAD drainage and the number of Aβ40-containing vessels	Nizari et al., 2021
		Taxifolin	Restores cerebrovascular reactivity and promotes Aβ clearance from brain to blood	Saito et al., 2021

AQP4: Aquaporin-4; Aβ: amyloid β; IPAD: intramural periarterial drainage; SMC: smooth muscle cell.