Table 1.
Activation of the Nrf2–Keap1 defence pathway in experimental stroke
| Strain and species | Experimental model | Findings | Reference |
|---|---|---|---|
| Sprague–Dawley rats | Permanent MCAO–intraluminal filament method | Nrf2 and HO-1 expression was up-regulated between 3 and 72 h after cerebral ischaemia. Curcumin, 100 mg kg−1i.p., 15 min after the onset of stroke reduced cerebral infarct, neurological deficit and brain oedema at 24 h of ischaemia. | Yang et al. (2009) |
| Sprague–Dawley rats | MCAO–intraluminal filament method for 90 min | tBHQ 16.7 mg kg−1i.p. three times (−24, −16 and −8 h) before stroke reduced infarct size and sensorimotor deficit at 24 h and 1 month after ischaemia–reperfusion. | Shih et al. (2005) |
| Wistar rats | MCAO–intraluminal filament method for 90 min | ICV infusion of tBHQ 1 mm for 72 h reduced cerebral infarct size and sensorimotor deficit at 24 h after ischaemia–reperfusion. | Shih et al. (2005) |
| Long–Evans rats | MCAO and CCAO: vessel clip for 3 h | Sulforaphane 5 mg kg−1i.p. 15 min after the onset of ischaemia decreased the infarct volume at 3 days of reperfusion. | Zhao et al. (2006) |
| ICR mice | MCAO: intraluminal filament method for 60 min | Stroke induced Nrf2 expression in neurons of the peri-infarct region between 2 and 72 h, peaking at 8 h. Keap1 expression declined after stroke in neurons of both the peri-infarct and infarct region between 2 and 72 h. | Tanaka et al. (2011) |
| CD1 mice | MCAO: intraluminal filament method for 90 min | Loss of Nrf2 function in KO animals increased cerebral infarct and neurological deficit at 24 h of reperfusion. | Shah et al. (2007) |
| C57B/SV129 mice | MCAO: permanent vessel cauterization | Loss of Nrf2 function in KO animals increased cerebral infarct at 7 days but not 24 h after ischaemia. | Shih et al. (2005) |
| C57B/SV129 mice | Intracortical injection of endothelin-1 | Neuroprotection by dietary 1% tBHQ observed in wild-type was lost in Nrf2−/− animals. | Shih et al. (2005) |
| C57BL/6 mice | MCAO: intraluminal filament method for 2 h | NEPP11 1 mg kg−1i.p. 1 h before and 4 h after the onset of stroke reduced brain infarct at 24 h of reperfusion. | Satoh et al. (2006) |
| C57BL/6 mice | MCAO: intraluminal filament method for 2 h | Carnosic acid 1 mg kg−1i.p. 1 h before the onset of stroke reduced cerebral infarct at 24 h of reperfusion. | Satoh et al. (2008) |
| C57BL/6 mice | MCAO: intraluminal filament method for 1 h | Plumbagin 3 mg kg−1i.v. 6 and 24 h before (but not 1 h after) the onset of stroke reduced cerebral infarct and neurological deficit at 72 h of reperfusion. | Son et al. (2010) |
| C57BL/6 mice | MCAO: intraluminal filament method for 90 min | Epicatechin given orally by gavage 30 mg kg−1 90 min before the onset of stroke reduced cerebral infarct and neurological deficit at 24 h of reperfusion, and this effect was lost in Nrf2-deficient animals. Post-treatment with the same dose and by the same route 3.5 h but not 6 h after the onset of stroke reduced cerebral infarct and neurological deficit at 72 h of reperfusion. | Shah et al. (2010) |
| C57BL/6 mice | Intra-striatal injection of NMDA | Epicatechin given orally by gavage 30 mg kg−1 90 min before the onset of stroke reduced NMDA-induced excitotoxicity at 48 h. | Shah et al. (2010) |
Abbreviations: CCAO, common carotid artery occlusion; HO-1, haem oxygenase-1; ICV, intracerebroventricular; i.p., intraperitoneal; i.v., intravenous; KO, knock-out; MCAO, middle cerebral artery occlusion; NEPP11, neurite outgrowth-promoting prostaglandin; NMDA, N-methyl-d-aspartate; Nrf2, nuclear factor erythroid 2-related factor 2; tBHQ, tert-butylhydroquinone.