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Table 3 Experimental stroke studies using Mas receptor agonists

From: Therapeutic potential of the renin angiotensin system in ischaemic stroke

Animals
Gender
Strain
Weight
Stroke model Treatment profile
MasR agonist
Administration
Time point
In vivo measures and methods Treatment outcome Proposed underlying mechanism Reference
Male
Sprague–Dawley rats
280–320 g
tMCAO
90 min
Up to 72 h recovery
Ang-(1–7)
i.c.v infusion
1 pmol/0.5 µl/h,
100 pmol/0.5 µl/h or 10 nmol/0.5 µl/h
Post treatment
NS: 6 point score Improved NS Increased NO and eNOS expression in ischaemic core and penumbral areas Zhang et al. [70]
Male
Sprague–Dawley rats
250–275 g
tMCAO
ET-1 model
3 day recovery
Ang-(1–7)
i.c.v infusion
1.1 nM; 0.5 μl/h
Pre and post treatment
BP: tail cuff
CBF: laser-Doppler
Infarct volume: TTC
NS: Bederson and Garcia scores
BHT: seed eating test
Did not affect BP or CBF
Did not affect CBF
Improved NS
Improved motor function
Decreased infarct volume
Decreased iNOS levels in ipsilateral hemisphere Mecca et al. [26]
Male
Sprague–Dawley rats
250–280 g
pMCAO
Filament model
24 h
Ang-(1–7)
i.c.v infusion
1.11 nM; 1 μl/h
Pre and post treatment
CBF: laser-Doppler
Infarct volume: TTC
NS: Bederson score
Did not affect CBF
Improved NS
Decreased infarct volume
Anti-oxidant and anti-inflammatory
Decrease in oxidative stress marker, malondialdehyde and increased SOD activity
Reduced expression of inflammatory markers NFκB, COX-2, TNF-α and IL-1β
Jiang et al. [71]
Male
Sprague–Dawley rats
250–275 g
tMCAO
ET-1 model
Up to 24 h recovery
Ang-(1–7)
1.1 nM; 0.5 μl/h
i.c.v infusion
Pre and post treatment
Infarct volume: TTC Decreased infarct volume Anti-inflammatory
Decrease in IL-1α, IL-6, CXCR4 as well as iNOS and microglia marker CD11b expression in ipsilateral cortex
Regenhardt et al. [17]
Male
Sprague–Dawley rats
250–280 g
pMCAO
Filament model
24 h recovery
Ang-(1–7 )
i.c.v infusion
1.1 nM; 0.25 μl/h
Pre-treatment
BP: Tail cuff method
CBF: laser-Doppler
NS: Bederson score
Infarct volume: TTC
Did not affect BP
Improved NS
Improved CBF
Decreased infarct volume
Pro-angiogenic
Increase in NO, eNOS and VEGF protein levels and capillary density markers CD31 in ipsilateral hemisphere
Jiang et al. [72]
Male
C57BL6/J mice
22–30 g
tMCAO
60 min
24 h recovery
AVE0991
i.p bolus
20 mg/kg
Post treatment
CBF: laser-Doppler
NS: Bederson score
BHT: Open field and parallel rod floor test
Infarct volume: Thionin staining
Did not affect CBF
Did not affect NS
Did not affect BHT
Did not affect infarct volume
Not discussed Lee et al. [73]
  1. Studies involved either transient middle cerebral artery (tMCAO) or permanent middle cerebral artery occlusion (pMCAO). Unless specified, tMCAO was performed via intraluminal filament model
  2. Ang-(1–7) angiotensin-(1–7), BHT behavioural testing, BP blood pressure, C21 compound 21, CBF cerebral blood flow, CD11b cluster differentiation 11b, CD31 cluster differentiation 31, COX-2 cyclooxygenase-2, CXCR4 C-X-C motif chemokine receptor type 4, eNOS endothelial nitric oxide synthase, ET-1 endothelin-1, i.c.v intracerebroventricular, IL-1α interleukin 1 alpha, IL-1β interleukin 1 beta, IL-6 interleukin 6, iNOS inducible nitric oxide synthase, i.p intraperitoneally, MasR Mas receptor, NFκB nuclear factor kappa B, NO nitric oxide, NS neurological score, SOD superoxide dismutase, TNF-α tumor necrosis factor alpha, TTC 2,3,5-triphenyltetrazolium chloride staining, VEGF vascular endothelial growth factor