Table 1.

TRPM2 channel in ischaemia‐reperfusion, chronic cerebral hypo‐perfusion and neonatal hypoxia‐ischaemia brain damage

Damage indicators	Models	Key observations	References
Neuronal death	OGD‐R	Neuronal death in cultured mouse cortical neurons was strongly inhibited by treatment with TRPM2 inhibitors before ischaemia and during ischaemia‐reperfusion. Neuronal death was significantly attenuated in cultured mouse cortical neurons infected with shRNA‐mediated knockdown of the TRPM2 expression.	58
	OGD‐R	Neuronal death in cultured mouse hippocampal neurons was markedly suppressed by treatment with TRPM2 inhibitors before ischaemia and during ischaemia‐reperfusion. Neuronal death in cultured mouse hippocampal neurons was also significantly attenuated by treatment with CTZ after reoxygenation. Neuronal death in cultured mouse hippocampal neurons was reduced by shRNA‐mediated knockdown of the TRPM2 expression.	59
	OGD‐R	Neuronal death in cultured mouse cortical neurons was reduced by TRPM2‐KO.	60
	OGD‐R	Neuronal death of CA1 pyramidal neurons in mouse hippocampal slices was prevented by TRPM2‐KO.	61
	MCAO‐R	Neuronal death in mice was significantly reduced by administration of CTZ after reperfusion.	64
	MCAO‐R	Neuronal death in the neocortex in mice was substantially attenuated by TRPM2‐KO.	63
	CP‐R	Neuronal death of CA1 pyramidal neurons in the hippocampus of mice was significantly lessened by injection of CTZ after resuscitation.	66
	BCCAO‐R	Neuronal death of CA1 pyramidal neurons in the hippocampus of mice was protected by TRPM2‐KO.	61
Infarction	MCAO‐R	Infarct volume in mice was significantly reduced by injections of CTZ after ischaemia and at the beginning of reperfusion. Infarct volume in the striatum in mice was significantly reduced by injection of lentivirus expressing TRPM2‐shRNA before ischaemia.	58
		Infarct volume in the ischaemia hemisphere in mice was significantly attenuated by TRPM2‐KO.	60, 62, 63
		Infarct volume in the ischaemia hemisphere was substantially alleviated by injection of CTZ after reperfusion in WT, but not TRPM2‐KO mice.	60
		Infarct volume in the ischaemia hemisphere was lessened by administration of tat‐M2NX prior to ischaemia in WT, but TRPM2‐KO mice. Infarct volume in the ischaemia hemisphere in mice was also lessened by administration of tat‐M2NX after reperfusion in adult and aged mice.	64
	MCAO	Infarct volume in mice after permanent ischaemia without reperfusion was not reduced by TRPM2‐KO.	62
	H‐I	Infarct volume in mouse puppies was reduced by TRPM2‐KO.	69
Atrophy	BCAS	White matter atrophy in mice was prevented by TRPM2‐KO.	68
Cognitive dysfunction	MCAO‐R	Neurological deficits in mice were significantly attenuated by TRPM2‐KO.	63
	BCCAO‐R	Impairments in learning and memory in mice were suppressed or prevented by TRPM2‐KO.	61
	BCAS	Impairments in cognitive function in mice were protected by TRPM2‐KO.	68
Sensorimotor dysfunction	H‐I	Sensorimotor dysfunction was mitigated in mouse puppies by TRPM2‐KO.	69

Abbreviations: BCAS, bilateral common carotid artery stenosis; BCCAO‐R, bilateral common carotid artery occlusion‐reperfusion; CA‐R, cardiac arrest‐resuscitation; CTZ, clotrimazole; H‐I, hypoxia‐ischaemia; MCAO‐R, middle cerebral artery occlusion‐reperfusion; ODG‐R, oxygen‐glucose deprivation; TRPM2‐KO, TRPM2‐knockout.