. 2022 Jul 6;7:215. doi: 10.1038/s41392-022-01064-1

Table 1.

Therapies targeting the related signaling pathways involved in the corresponding pathophysiology in ischemic stroke

Drug/Therapy	Targeting signaling pathway	Major targeting pathophysiology	Authors	Citations	Applications
NA-1	GluN2B-PSD95-nNOS	Excitotoxicity	Chen et al.	³³³	Animals/Neuronal cultures
ZL006	GluN2B-PSD95-nNOS	Excitotoxicity	Zhou et al.	⁴²⁶	Mice/rat MCAO
IC87201	GluN2B-PSD95-nNOS	Excitotoxicity	Lai et al.; Bach et al.	^27,427	In vitro
Tat-p53DM	DAPK1	Excitotoxicity	Pei et al.	³⁴⁹	Animals/Neuron in vitro
GluN2B^{CT1292–1304}	DAPK1/ GluN2B-PSD95-nNOS	Excitotoxicity	McQueen et al.	³⁵¹	Animals/Neuron in vitro
Tat-K13	PTEN	Excitotoxicity	Zhang et al.	⁷⁵	Rat focal ischemia
Geniposide	GluN2A/AKT/ERK	Excitotoxicity	Huang et al.	³⁵²	Rat tMCAO
Electroacupuncture	PI3K/Akt	Excitotoxicity	Kim et al.	⁴²⁸	Animals/rat
Pseudoginsenoside-F11	Akt-Creb	Excitotoxicity	Liu et al.	³⁵³	Rat MCAO
TRPM2 (Gene knockout)	Akt/ERK	Excitotoxicity	Alim et al.	³⁵⁴	Mice MCAO
Tat-Panx308	Panx1	Excitotoxicity	Weilinger et al.	⁴²⁹	Mice/Rat brain slices
tBHQ	Nrf2/ARE	Oxidative stress	Hou et al.	³⁵⁸	Rat MCAO
Trans sodium crocetinate (TSC)	SIRT3/FOXO3a/SOD2	Oxidative stress	Chang et al.	³⁶⁴	Rat MCAO
Genipin	UCP2-SIRT3	Oxidative stress	Zhao et al.	³⁶⁵	Mice MCAO
CCL2/CCR2 gene knockout	CCL2/CCR2	Neuroinflammation	Wattananit et al.; Dimitrijevic et al.	^263,367	Animals/mice MCAO
Resveratrol	TLR4/NF-Kb/STAT3	Neuroinflammation	Ghazavi et al.; Rahimifard et al.	^369,370	Rat MCAO
Stevioside	TLR/NF-kB	Neuroinflammation	Zan et al.	³⁷²	Rat TBI
Progesterone	TLR4/NF-kB	Neuroinflammation	Hsieh et al.; Li et al.; Wang et al.	^373–375	Rat MCAO
Tak242	TLR4	Neuroinflammation	Abdul et al.	⁴³⁰	Rat/In vitro
Isoquercetin	TLR4	Neuroinflammation	Shi et al.; Wang et al.	^431,432	Animals/In vitro
Propofol	TLRs	Neuroinflammation	Gui et al.; Marik et al.	^433,434	In vitro BV2/Review
Dexmedetomidine	HMGB1/TLR4/NF-kB	Neuroinflammation	Zhai et al.	³⁷⁶	Rat MCAO
XPro1595	TNFs	Neuroinflammation	Clausen et al.	³⁷⁸	Mice MCAO
cTfRMAb-TNFR	TNFs	Neuroinflammation	Zhou et al.; Sumbria et al.	^379,380	Mice MCAO
Stnf-Αr1	TNFs	Neuroinflammation	Liguz-Lecznar et al.	³⁸¹	Mice MCAO
Quercetin	Sirt	BBB	Yang et al.	⁴³⁵	Rat MCAO
Minocycline	Sirt3/proline hydroxylase-2/MMP	BBB	Yang et al.	³⁹⁶	HBMECs/Rat hypobaric hypoxia
Hydrogen sulfide	MMP9	BBB	Liu et al.	³⁹⁷	Mouse MCAO
Vagus nerve stimulation	MMP2/9	BBB	Yang et al.	³⁹⁸	Rat MCAO
Hyperbaric oxygen	MMP2	BBB	Michalski et al.	³⁹⁹	Rat MCAO
Metformin	AMPK	BBB	Liu et al.	¹⁰⁴	Mice MCAO
OPC transplantation	Wnt-5a	BBB	Khan et al.	⁴⁰⁰	Rat MCAO
Patchouli alcohol	MAPK	BBB	Wei et al.	⁴³⁶	Mice MCAO
DL-3n-butylphthalide (NBP)	MAPK/AQP4/MMP9	BBB	Mamtilahun et a l.	⁴³⁷	Rat MCAO
FTY720	Akt	Autophagy	Hasegawa et al.; Wei et al.	^401,402	Rat MCAO
Hydroxysafflor	Akt	Autophagy	Qi et al.	⁴³⁸	Rat MCAO
Selenium	PI3K/Mtor/Akt	Autophagy?	Yang et al.	⁴⁰⁴	Rat MCAO
Electroacupuncture	PI3K/Akt	Autophagy	Wang et al.	⁴³⁹	Rat MCAO
DHL	PI3K/Mtor/Akt	Autophagy	Meng et al.	⁴⁴⁰	In vitro OGD/R
Diosgenin	STAT2/HIKESHI	Autophagy	Zhang et al.	⁴⁴¹	Rat MCAO
Stem cell-secreted vesicles	STAT3	Autophagy	Xia et al.	⁴¹¹	Rat MCAO/In vitro
Melatonin	PI3K-Akt	Autophagy	Yang et al.	⁴⁴²	Rat MCAO
MTMR14	PTEN	Autophagy	Pan et al.	⁴⁴³	Mice MCAO/In vitro
Sevoflurane	PTEN/AKT1/Mtorc1	Autophagy	Xue et al.	⁴⁴⁴	Rat MCAO
Remote ischemic preconditioning	PTEN/AKT1	Autophagy	Zhong et al.	⁴⁴⁵	Mice MCAO
Neuroprotectin D1	Wnt/β-catenin	Autophagy	Mu et al.	⁴⁴⁶	In vitro OGD/R
Electropuncture	Wnt	Autophagy	Chen et al.	⁴⁴⁷	MCAO Rat
SMXZF	AMPK-mTOR	Autophagy	Guo et al.; Wang et al.	^405,406	Mice MCAO/In vitro
Puerarin	AMPK/Mtorc/ULK1	Autophagy	He et al.	⁴⁴⁸	Rat MCAO
Electroacupuncture	SIRT-FOXO1	Autophagy	Xu et al.	⁴¹³	Rat MCAO
Luteolin	SIRT3/AMPK/Mtor	Autophagy	Liu et al.	⁴¹⁴	Rat MCAO
Melatonin	SIRT1-BMAL1	Autophagy	Liu et al.	⁴¹⁵	Mice MCAO
Proanthocyanidins	ERK	Apoptosis	Fu et al.	⁴⁴⁹	Mice MCAO
Beta-hydroxybutyrate	ERK/CREB/eNOS	Apoptosis	Li et al.	⁴¹⁶	Rat MCAO/In vitro
MCC950	NLRP3	Apoptosis/Inflammasome	Ye et al.	³⁹²	Mice MCAO
Genistein	NLRP3	Apoptosis	Wang et al.	³⁹³	Mice MCAO
BML-275	AMPK	Apoptosis	Hu et al.	⁴²⁰	Mice MCAO
Glycine	AMPK/GSK-3β/HO-1	Apoptosis	Chen et al.	⁴²¹	In vitro OGD/R
Apelin-13	AMPK	Apoptosis	Yang et al.	⁴⁵⁰	Mice MCAO
CTRP3	AMPK/SIRT1-PGC-1α	Apoptosis	Gao et al.	⁴⁵¹	In vitro OGD/R
Rosuvastatin	Sirt1/NF-kB	Apoptosis	Yan et al.	⁴²²	Rat MCAO
Salvianolic acid B	SIRT1	Apoptosis	Lv et al.	⁴⁵²	Rat MCAO
Stem cell therapy	SIRT-NFkB	Apoptosis	Sarmah et al.	⁴⁵³	Rat MCAO
	MiRNA-29b/SIRT1/PGC-1	Apoptosis	Xu et al.	⁴²⁴	In vitro
Tetrahedral frameword nucleic acids	TLR2-MyD88-NF-kappa B	Apoptosis	Zhou et al.	⁴⁵⁴	Rat MCAO/In vitro
Chinese drugs	TLR4/MyD88/MAPK/NF-kappaB	Apoptosis	Gu et al.	⁴⁵⁵	Rat MCAO