Intracranial artery patency was observed in 12.2% of TACI patients evaluated within 4.5 h. Although absence of ILVO was associated with slightly better prognosis, more than half had a poor outcome at 3 months.
Angiogenesis is the process of new blood vessel growth from pre-existing vascular structures. The new vessels from atherosclerotic lesions may be a focus of instability, since they facilitate the infiltration of inflammatory cells and due to their tendency to leak, they may produce haemorrhagic complications. Pentameric C-reactive protein (CRP), a strong marker of inflammation, is a risk factor for cardiovascular diseases with a direct role in the development of atherosclerotic lesions. In hypoxic tissue damage, CRP dissociates irreversibly into monomeric CRP (mCRP), which was previously demonstrated to be pro-angiogenic on bovine aortic endothelial cells (BAEC). Our main study was to examine the vessel forming capability of CRP in the presence of other angiogenic factors known to be present in the micro-environment of unstable plaques with immature vasculature. Here we studied the effects of mCRP in presence or absence of FGF-2 on BAEC proliferation, migration, tube formation in Matrigel and on the vascular remodelling using spheroids, a tri-dimensional system of endothelial cell culture embedded in collagen gel. A significant synergic effect of mCRP combined with FGF-2 was observed in all angiogenesis assays used, compared to the effect of mCRP or FGF-2 alone. Using the spheroids, both mCRP and FGF-2 stimulated the length of sprouts with endothelial cells more dispersed giving an aspect of thin structures. For a better understanding of the molecular mechanisms involved, the signalling pathways were investigated by Western blotting and all the assays were performed in the presence or absence of pharmacological inhibitors of MAPK (PD98059), γ-secretase (DAPT inhibitor) and phosphatidylinositol 3-kinase (PI3K) pathways (LY294002). We showed mCRP-induced endothelial cell proliferation, migration and tube formation required activation of the PI3K pathway. MAPK activation was essential in mCRP-induced cell proliferation and differentiation (tube formation and sprouting from the core of spheroids) and γ-secretase activity was required for mCRP-induced tube formation only. For its pro-angiogenic activity, FGF-2 required all of these key pathways with the exception that γ-secretase activity was not associated with FGF-2-induced cell migration. In all assays including the over-expression of phospho-ERK, the synergistic pro-angiogenic effect of mCRP added to FGF-2 was completely inhibited by LY294002. Thus, mCRP and FGF-2 have a common signalling pathway through PI3K and an eventual deregulation of their pro-angiogenic effects due to an excessive inflammation inducing a hyper-vascularisation which could contribute to formation of unstable plaque with haemorrhagic risk, and therefore, might be prevented by targeting the key proteins of the PI3K pathway.
BACKGROUND Our goal is to evaluate whether the administration of thrombolytic treatment has varying effects on clinical and radiological outcomes in patients with large‐vessel occlusion stroke, based on the type of stroke center where the treatment was given (thrombectomy‐capable center versus local stroke center). METHODS We included patients with an acute ischemic large‐vessel occlusion stroke who were directly admitted to thrombectomy‐capable centers and treated with endovascular thrombectomy, or were transferred from local stroke centers as thrombectomy candidates, in Catalonia, Spain, between 2017 and 2021. The primary outcome was the shift analysis on the modified Rankin scale score at 90 days. Secondary outcomes included death at 90 days and the rate of parenchymal hemorrhage and successful reperfusion. Inverse‐probability weighting clustered at the type of stroke center was used to estimate the effects. RESULTS The analysis included 2268 patients directly admitted to thrombectomy‐capable centers, of whom 975 (49%) were treated with thrombolysis, and 938 patients transferred from local stroke centers, of whom 580 (66%) were treated with thrombolysis and 616 (67%) were treated with thrombectomy. Mean age was 72 (SD ±13) years, median National Institute of Health Stroke Scale score was 17 (interquartile range, 12–21), and 1363 patients were women (48%). Patients treated with intravenous thrombolysis were younger, had shorter time from onset to first image, higher Alberta Stroke Program Early Computed Tomography Score, and lower rates of wake‐up stroke, atrial fibrillation, and anticoagulation intake. Patients treated with thrombolysis had better functional outcome at 90 days, with no difference between patients directly admitted to thrombectomy‐capable centers (adjusted common odds ratio [acOR], 1.50 [95% CI, 1.24–1.81]) and patients transferred from local stroke centers (acOR, 1.44 [95% CI, 1.04–2.01]). Patients treated with intravenous thrombolysis had lower death rate, higher rate of parenchymal hematoma, and similar rate of successful reperfusion, with no difference according to type of center ( P interaction >0.1). CONCLUSION Administration of intravenous thrombolysis in patients with a large‐vessel stroke with intention of thrombectomy was associated with lower degrees of disability, lower death rate, and higher rates of parenchymal hematoma both in thrombectomy‐capable centers and in local stroke centers.
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