Neuroprotective Role of the Nrf2 Pathway in Subarachnoid Haemorrhage and Its Therapeutic Potential

Table 1

A summary of findings from experimental subarachnoid haemorrhage studies testing agents that activate the Nrf2 pathway, with relevant human data for these agents.

Agent	Curcumin	Astaxanthin	Lycopene	tert-Butyl hydroquinone	Dimethyl fumarate	Melatonin	Erythropoietin	Sulforaphane
Animal SAH model	Rat, mouse	Rat, rabbit	Rat	Rat	Rat	Rat	Rat, rabbit	Rat
Timing of administration	0-4 weeks	30 min-3 h	2 h	0-36 h	Twice daily for 2 d	0-48 h	0-72 h	30 min-72 h
Method of administration	IP	IT & oral	IP	IP & oral	Oral	IP	SC, IV, & IP	IP
Animal dose	150-600 mg/kg	0.01-75 mg/kg	40 mg/kg	12.5-50 mg/kg	15 mg/kg	15-150 mg/kg	400-1000 IU/kg	5 mg/kg
Time of tissue evaluation	Days 3-7	24-72 h	24 h	24-48 h	48 h	24-48 h	24-72 h	12-72 h
Time of clinical assessments	6 h—day 7	0-72 h	24 h	Day 0-8	Days 2-5	24-48 h	Days 0-16	72 h
Biochemical effect	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Clinical effect	Yes	Yes	Yes	Yes	Yes	Yes	Yes	Yes
Reduced vasospasm	Yes	Yes	Not assessed	Not assessed	Not assessed	Yes	Yes	Yes
Method of administration in humans	Oral	Oral	Oral	Oral	Oral	Oral	IV	Oral
Half-life	6-7 h [202]	[203]	28-61 h [204]	20-24 h [205]	12 min [206]	1.8-2.1 h [207]	6-9 h [201]	2.4-2.6 h [208]
BBB permeability	Yes [209]	Yes [210]	Yes [211]	Yes [212]	Yes [213]	Yes [214]	Yes [215]	Yes [163]
Toxicity	None known [216]	None known [217]	None known [204]	None known [218]	Progressive multifocal leukoencephalopathy & painful dermatitis [219]	None known [220]	Polycythaemia & secondary stroke [201]	None known

Details of the experimental studies are shown in Table 2.