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] |