Abstract
Objective The Notch signaling pathway is involved in angiogenesis induced by brain ischemia and can be efficiently inhibited by the γ-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT). The aim of the present study was to noninvasively investigate the effect of DAPT treatment on angiogenesis in brain repair after stroke using magnetic resonance imaging (MRI). Methods Sprague-Dawley rats (n = 40) were subjected to 90 minutes of transient middle cerebral artery (MCA) occlusion and treated with PBS (n = 20) or DAPT (n = 20) at 72 hours after the onset of ischemia. MRI measurements including T2-weighted imaging (T2WI), susceptibility-weighted imaging (SWI), and cerebral blood flow (CBF) were performed at 24 hours after reperfusion and weekly up to 4 weeks using a 3-Tesla system. Histological measurements were obtained at each time point after MRI scans. Results SWI showed that DAPT treatment significantly enhanced angiogenesis in the ischemic boundary zone (IBZ) with respect to the control group, with local CBF in the angiogenic area elevated, along with increases in vascular density confirmed by histology. Conclusion Treatment of ischemic stroke with DAPT significantly augments angiogenesis, which promotes poststroke brain remodeling by elevating CBF level, and these processes can be dynamically monitored and evaluated by MRI.
Highlights
Stroke is a major cause of mortality and disability globally while thrombolytic therapy as a fundamental treatment is not ideal for various restrictions and complications [1]
There is an increasing amount of studies that focus on the endogenous brain repair processes after stroke, which constitute the basis of neurorestorative therapy
These areas were detected as having low intensity on the susceptibility-weighted imaging (SWI) map (Figures 3(b) and 3(e)), which had appeared at 2 weeks in the two groups, as indicated by red arrows
Summary
Stroke is a major cause of mortality and disability globally while thrombolytic therapy as a fundamental treatment is not ideal for various restrictions and complications [1]. Neuroprotection as an alternative approach, which targets the cerebral parenchyma, is aimed at preserving cerebral tissue viability from reduced CBF. It seems to be a promising option for acute ischemic stroke (AIS) treatment. There is an increasing amount of studies that focus on the endogenous brain repair processes after stroke, which constitute the basis of neurorestorative therapy. As an essential part of biological substrates for poststroke brain remodeling, angiogenesis induced by brain ischemia enhances blood flow and nutrient supply to the affected tissue, which may benefit functional recovery [2, 3]. Neurorestorative treatments of either cell-based or pharmacological therapies promote angiogenesis, which is associated with
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