From: Therapeutic potential of the renin angiotensin system in ischaemic stroke
Animals Gender Strain Weight | Stroke model | Treatment profile AT2R agonist Administration Dose Time point | In vivo measures and methods | Treatment outcome | Proposed underlying mechanism | Reference |
---|---|---|---|---|---|---|
Male Wistar rats 280–320 g | tMCAO 90 min or 3 h 24 h or 7 day recovery | C2 1 i.p bolus 0.03 mg/kg Post treatment | BP: telemetry method NS: Bederson score BHT: Beam walk, paw grasp, rotarod test, grip strength Infarct volume: TTC Haemoglobin content | Did not affect BP Improved NS Improved functional outcome Decreased infarct volume Decreased haemorrhage | Pro-angiogenic Via Akt/eNOS/NO pathway Upregulation of p-Akt, IL-10, BDNF and eNOS protein expression. Plus, nitrative stress markers nitrotyrosine and iNOS protein expression were downregulated in the ipsilateral hemisphere The results were further correlated to a decrease in AT1R and an upregulation of AT2R cerebral expression | Alhusban et al. [60] |
Male Wistar rats 250–310 g | tMCAO or pMCAO Filament model Up to 21 days recovery | C21 i.p bolus 0.3 mg/kg/day Post treatment | NS: 7 point score Infarct volume: Nissl staining | For pMCAO treated rats Improved NS Decreased infarct volume | Pro-angiogenic Increased VEGF expression due to Akt/mTOR signalling pathway activation | Mateos et al. [61] |
Male Sprague–Dawley rats 250–275 g | tMCAO ET-1 model 3 day recovery | C21 i.c.v or i.p infusion 0.0075 μg/μl/h i.c.v 0.03 or 0.1 mg/kg i.p Pre and post treatment | BP: tail cuff method CBF: laser-Doppler Infarct volume: TTC NS: Bederson and Garcia scores | Did not affect BP Did not affect CBF Improved NS Decreased infarct volume | Anti-inflammatory Decrease in gene expression for inflammatory markers iNOS, CCR2 and its ligand CCL2 in ipsilateral cerebral cortex | Joseph et al. [62] |
Male SHR 270–320 g | tMCAO ET-1 model 3 day recovery | CGP42112 i.c.v infusion 0.1–10 ng/kg/min Pre and post treatment | BP: tail cuff method Infarct volume: ballistic light method BHT: ledged beam test | Did not affect BP Improved motor function Decreased infarct volume | Anti-oxidant Decreased superoxide production in infarcted cortical regions, associated to an increase in brain AT2R expression | McCarthy et al. [63] |
Male SHR Weight not specified | tMCAO ET-1 model 3 day recovery | CGP42112 i.c.v injection 3 μg/kg Post treatment | BP: tail cuff method Infarct volume: ballistic light method BHT: ledged beam test | Did not affect BP Improved motor function Decreased infarct volume | Anti-apoptotic Decreased cleaved caspase-3 positive apoptotic cells and increased neuronal survival (NeuN positive cells) in ipsilateral hemisphere. Plus, increased activated microglia (OX42 marker) in ipsilateral core | McCarthy et al. [64] |
Male SHR 330–350 g | tMCAO ET-1 model 3 day recovery | C21 i.c.v infusion and injection 3 μg/kg Pre and post treatment | BP: tail cuff method Infarct volume: ballistic light method BHT: ledged beam test | Did not affect BP Improved motor function Decreased infarct volume | Anti-apoptotic and vasodilatory Increased neuronal survival (NeuN positive cells) and activated microglia which are potentially BDNF positive Myography studies in basilar arteries further suggested a vasodilatory effect induced by C21 | McCarthy et al. [65] |
Male C57BL/6J 8–12 weeks | tMCAO 30 min 24 h recovery | CGP42112 i.p bolus 1 mg/kg Post treatment | CBF: laser-Doppler NS: Bederson score BHT: hanging wire test Infarct volume: thionin staining Cerebral oedema | Did not affect cerebral oedema Improved NS Improved motor function Improved CBF Decreased infarct volume | Anti-apoptotic C21 promotes cell viability in primary cortical neurons following oxygen glucose depravation challenge | Lee et al. [66] |
Male C57BL/6J WT and AT2R KO mice 25–30 g | pMCAO dMCAO model 24 h recovery | C21 i.p bolus 10 µg/kg/day Pre and post treatment | BP: tail cuff method NS: 4 point score CBF: laser speckle method Infarct volume: MRI T2 scan Cerebral oedema Blood brain barrier (BBB) permeability: Evans blue dye | Did not affect BP Improved NS Improved CBF Decreased infarct volume Decreased oedema Decreased BBB permeability | Ant-inflammatory Decreased expression of MCP-1, TNF-α and SO Also observed reduced BBB breakdown | Min et al. [67] |