Table 2.

Protective roles of H₂S donors in neurological disease models

H2S donor	Relevant disease	Study approach	Regime of H2S donor treatment	References
ACS84	PD	1. SHSY-5Y exposed to 6-hydroxydopamine (6-OHDA) 2. Male Sprague-Dawley rats 6-OHDA hydrobromide was unilaterally injected into the left striatum.	1. ACS84 1 h prior the administration of 6-OHDA. 2. ACS84 (10 mg/kg/day) from the 5th to 7th week after 6-OHDA lesion.	[41]
ADT-OH	Stroke	Adult male C57BL/6J mice. 1. (MCAO) 2 h occlusion followed by reperfusion. 2. Hyperglycaemia MCAO model of tPA-enhanced haemorrhagic transformation.	ADT-OH (50 mg/kg) was administered at the onset of reperfusion or when the tPA infusion began	[55]
		Male ICR mice. MCAO was induced by an intraluminal monofilament technique.	ADT-OH (50 mg/kg/day) was administered after 3 h of reperfusion via intraperitoneal injection.	[54]
AP39	AD	1. Heterozygous APP/PS1 double-transgenic mice (APPswe-PS1dE9). 2. Primary cultures of cortical neurons from hemizygous transgenic mice and non-transgenic littermates.	1. AP39 (100 nM/kg) daily intraperitoneal injection for 6 weeks prior to the experiments. 2. Primary neurons were treated with AP39 (25–250 nM) for 24 h.	[49]
	Stroke	Male Sprague-Dawley rats subjected to MCAO.	Pre-treatment with AP39 50-nmol/kg during days, with the last dose 72 h before ischemia.	[98]
Carbazole-based H2S donor (C15H14N2S)	Epilepsy	Male Sprague–Dawley rats subjected to intraperitoneal injection of PTZ (40 mg/kg).	Carbazole-based H2S donor (500 µM) injected into the lateral ventricle, 1 h after PTZ administration.	[64]
Diallyl disulphide (DAD) and diallyl trisulfide (DAT)	GBM	Human T98G cells Human U87 cells	DAD (100 µM) for 24 h. DAT (25 µM) for 24 h.	[59]
		Ectopic glioblastoma Induction in NOD.CB17-prkdcscid/J mice by subcutaneous implantation of U87MG cells.	DAT (10ug/kg, 100ug/kg, and 10 mg/kg) 7 daily oral treatments for 4 weeks.	[99]
GYY4137	AD	3xTg-AD mice. These mice overexpress mutant human APP, PS1 and tau protein.	GYY4137 (100 mg/kg) injected intraperitoneally for 12 weeks.	[46]
	MS	1. C57BL/6 mice 2. Dark Agouti rats Immunised with 0.5 mg/mL guinea pig myeline oligodendrocyte glycoprotein. Lymph nodes were isolated after 7 days.	GYY4137 (200 µM) lymph nodes were cultured in the presence of GYY4137 from 40 min to 12 h.	[66]
	Stroke	Sprague–Dawley rats. Transient middle cerebral artery occlusion (tMCAO) model. 1.5 h ischemia and 24 h reperfusion	GYY4137 (1 mM in 5µL) was injected in the lateral cerebral ventricle just before reperfusion	[100]
Sodium hydrosulphide (NaHS)	PD	SHSY-5Y exposed to MPP+ (500 µM) for 24 h. Male C57BL/6J mice. MPTP (20 mg/kg) was subcutaneously injected daily for 5 days.	NaHS at 50, 100, 200, 400 µM administered 30 min prior MPP+. From days 4–8, NaHS was injected intraperitoneally (5.6 mg/kg) for 10 days, 30 min prior MPTP.	[40] [42]
	AD	3xTg-AD mice.	NaHS (0.5 mg/kg) was administered intraperitoneally once daily for 12 weeks starting at 6 or 12 months of age.	[47]
	Stroke	Sprague-Dawley rats. Adult male C57BL/6J mice subjected to tMCAO. 1) MCAO 2 h occlusion followed by reperfusion. 2) Hyperglycaemia MCAO model of tPA-enhanced haemorrhagic transformation.	NaHS (25 µmol/kg dissolved in 2.5 ml of saline) administrated via intravenous injection 1 and 30 min before reperfusion. NaHS (25 µmol/kg) was administered at the onset of reperfusion or when the tPA infusion began.	[52] [55]
	GBM	Rat C6 glioma cell line	NaHS (0.25, 0.5 and 1 mM) for 48 h	[58]
S-ASP (sulphur-aspirin hybrid) and S-DI (sulphur-diclofenac)	AD and PD	Primary human microglial cells, primary human astrocytes and cell lines: THP-1, U118, SHSY-5Y exposed to: 1. CBS inhibitor hydroxylamine 1 mM. 2. LPS at 1 µg/mL and IFN-γ at 333 U/mL.	S-ASP and S-DI administered at 1,3, 10, 30, and 50 µM for 2, 4, 8, or 12 h.	[101]
Sodium sulphide (Na2S)	AD	SHSY-5Y exposed to HEWL aggregates (lysozyme)	Na2S (12 mM) was administered in a molar ratio of 1:5 (HEWL:H2S) for 24 h.	[48]
	Stroke	1. Sprague-Dawley rats subject to MCAO. 2. C57BL/6 mice subject to acute cerebral anoxia.	1. Rats received Na2S (5, 10, 20, 40 mg/kg) via intravenous injection within 15 min of MCAO. 2. Mice received Na2S (7.5, 15, 30 mg/kg) via intravenous injection within 15 min after hypoxic anoxia.	[102]
	GBM	Human T98G cells Human U87 cells	Na2S (476 µM) for 4 h.	[57]
S-Propargyl-cysteine	AD and PD	Male Sprague-Dawley rats subjected to LPS bilateral intracerebroventricular injection.	S-Propargyl-cysteine (20, 40, 80 mg/kg) administered once per day three days before LPS insult and thereafter continuously for 9 days.	[50]
Sulphur water	AD	3xTg-AD mice.	Sulphurous water (thermal water with high H2S content, 125 mg/L) was administered intraperitoneally (12 mL/kg) daily for 12 weeks.	[47]
Tacrine-H2S	AD	Kunming mice subjected to aluminium chloride (AlCl3) model of AD by intraperitoneal injection (AlCl3: 100 mg/kg), every other day for 50 days.	Tacrine-H2S: (5 and 15 mmol/kg/day) via intraperitoneal injection for 20 days after AlCl3 treatment.	[103]