Table 2. Angiogenic interventions in experimental stroke research.
| Treatment | Author | Species | Ischemia model | Assessment techniques | End points |
|---|---|---|---|---|---|
| EPO | Wang et al126 | Wistar rats | Embolic MCAO | Immunohistochemical analysis of FITC-dextran perfused vessels | Increased number of capillary segments at the ischemic boundary |
| Atorvastatin | Chen et al127 | C57BL/6J mice | pMCAO | Immunohistochemical analysis for BrdU and vWF (marker of ECs) double staining | Increased vessel density at 14 days |
| Physical activity and exercise | Gertz et al128 | C57BL/6J mice | tMCAO for 30 minutes | Double histochemical staining for cell proliferation marker, BrdU, and vWF (marker of ECs) | Increased vessel density in the ischemic striatum at 4 weeks |
| Niaspan (Niacin) | Chen et al129 | Wistar rats | tMCAO for 2 hours | Double immunostaining for cell proliferation marker, BrdU, and endothelial cells (vWF) | BrdU-positive endothelial cells were significantly increased in the ipsilateral hemisphere together with increased vascular perimeter and density |
| Sildenafil | Ding et al130 | Wistar rats | Embolic MCAO | Magnetic resonance imaging | Increased angiogenesis at 6 weeks |
| Niaspan (Niacin) | Ye et al105 | Streptozotocin induced type 1 diabetes in Wistar rats | tMCAO for 2 hours | Immunostaining for vWF (marker of ECs) and α-SMA (marker of VSMCs) in addition to costaining with BrdU (proliferation marker) | Increased vascular and arterial density as well as increased vessel perimeter and arterial diameter in the ischemic brain, in addition to a significant increase in vascular endothelial cells proliferation |
| Candesartan | Guan et al99 | Wistar rats | tMCAO for 3 hours | Immunohistochemical analysis for laminin | Increased cerebrovascular density in both hemispheres at 7 days |
| Valproate | Wang et al131 | Sprague-Dawley rats | tMCAO for 60 minutes | Double staining for the proliferation marker, Ki67, and endothelial cells (RECA-1) | Increased microvessel density in the ipsilateral cortex at 14 days |
| Simvastatin and human umbilical cord blood cells combination | Cui et al124 | Wistar rats | tMCAO for 2 hours | Double immunofluorescent staining for BrdU (marker of proliferating cells) and vWF (marker of ECs) | Vascular density and perimeter were significantly increased together with a significant increase in the percentage of BrdU-ECs in the ischemic hemisphere |
| GW3965 (synthetic liver X receptor agonist) | Cui et al125 | C57BL/6J mice | tMCAO for 2.5 hours | Double immunofluorescent staining for BrdU (marker of proliferating cells) and vWF | GW3965 treatment significantly increased the vascular density and the perimeter of vWF vessels and the percentage of BrdU-ECs in vessels |
| GM6001 pan-MMP inhibitor | Yang et al132 | Spontaneously hypertensive rats (SHRs) | tMCAO for 90 minutes | Counting microvessels labeled with RECA-1 (marker of ECs) | Increased number of vessels in the peri-infarct area at 3 weeks |
Epo, erythropoietin; BrdU, bromodeoxyuridine; ECs, endothelial cells; α-SMA, α-smooth muscle actin; tMCAO, temporary middle cerebral artery occlusion; pMCAO, permanent middle cerebral artery occlusion; VSMCs, vascular smooth muscle cells; MMP, matrix metalloproteinase; FITC, fluorescein isothiocyanate; vWF, von Willebrand factor; RECA-1, rat endothelial cell antigen.