The effect of angiopoietin-1 upregulation on the outcome of acute ischaemic stroke in rodent models: A meta-analysis

Clinical studies report that low circulating angiopoietin-1 concentration at presentation predicts worse outcomes after ischaemic stroke. Upregulating angiopoietin-1 may therefore have therapeutic benefit for ischaemic stroke. This systematic review assessed whether upregulating angiopoietin-1 improved outcomes in rodent models of ischaemic stroke. Random-effects models quantified the effect of angiopoietin-1 upregulation on stroke severity in terms of the size of cerebral infarction and the extent of blood–brain barrier permeability. Eleven studies utilising rat and mouse models of ischaemic stroke fulfilled the inclusion criteria. Meta-analyses demonstrated that angiopoietin-1 upregulation significantly reduced cerebral infarction size (standardised mean difference: –3.02; 95% confidence intervals: –4.41, –1.63; p < 0.001; n = 171 animals) and improved blood–brain barrier integrity (standardized mean difference: –2.02; 95% confidence intervals: –3.27, –0.77; p = 0.002; n = 129 animals). Subgroup analyses demonstrated that angiopoietin-1 upregulation improved outcomes in models of transient, not permanent cerebral ischaemia. Six studies assessed the effect of angiopoietin-1 upregulation on neurological function; however, inter-study heterogeneity prevented meta-analysis. In conclusion, published rodent data suggest that angiopoietin-1 upregulation improves outcome following temporary cerebral ischaemia by reducing cerebral infarction size and improving blood–brain barrier integrity. Additional research is required to examine the effect of angiopoietin-1 upregulation on neurological function during stroke recovery and investigate the benefit and risks in patients.