TABLE 1.

Summary of previous studies of S1P receptor modulators in experimental intracerebral haemorrhage.

	Rolland et al., 2011	Rolland et al., 2013		Lu et al., 2014	Bobinger et al., 2019
Drug, dose, route	Fingolimod, 1 mg/kg, i.p	Fingolimod, 1 mg/kg, i.p		Fingolimod, 0.5 mg/kg, i.p	• Siponimod, 0.3 mg/kg, i.p. • Siponimod, 3 mg/kg, i.p
Treatment regimen	1 h after surgery	• 1 h after surgery. • 1 h after surgery and once daily on the following two days		30 min after surgery and once daily on the following two days	• 30 min after surgery. • 30 min after surgery and once daily on the following two days
Sex, strain, species	CD-1 mice (sex not reported)	Male CD-1 mice	Male Sprague-Dawley rats	Male CD1 mice	Male C57BL/6 mice
Model	Collagenase	• collagenase. • autologous blood	Collagenase	Collagenase	Collagenase
Group sizes	5 or 10	7	9–10	10
Histological outcome
Edema	Wet-dry: p < 0.05 (D1 and D3)	Wet-dry: p < 0.05 (D1 and D3)		Wet-dry: p < 0.05, D3 (n = 5)	• MRI: p = 0.02 at D3 (multiple dosage). • Wet-dry: p = 0.022, p = 0.0013, p = 0.04 for single and multiple 0.3, and multiple 3 mg/kg doses
Atrophy/tissue loss			p < 0.05 at 10 weeks	p < 0.01, D14
Apoptotic cells				p < 0.05, D3
Behavioral outcome
Composite neuroscore	p < 0.05 D1 and D3	p < 0.05 D1 and D3		p < 0.05, D3	No effect at D1 p = 0.03 at D3
Wire hanging	p < 0.05 (D1) n.s. (D3)	p < 0.05 (D1)* n.s. (D3)*		p < 0.05, D3 and D14
Beam balance	p < 0.05 (D1). n.s. (D3)	p < 0.05 (D1)* n.s. (D3)*
Forelimb use asymmetry		n.s at D1 and D3*
Corner test		p < 0.05 D1 and D3
Paw placement		p < 0.05 D1 and D3	p < 0.05 D1 and D2. No effect at D3 and 10 weeks
Weight loss				p < 0.01 (D1), p < 0.05 (D3)	p = 0.036 (multiple 0.3 mg/kg). p = 0.048 (multiple 3 mg/kg)
Survival				No effect	p = 0.037 (multiple 0.3 mg/kg doses)

^*Test only performed in the collagenase model.