Protective effects of angiopoietin-like 4 on cerebrovascular and functional damages in ischaemic stroke

AIMS: Given the impact of vascular injuries and oedema on brain damage caused during stroke, vascular protection represents a major medical need. We hypothesized that angiopoietin-like 4 (ANGPTL4), a regulator of endothelial barrier integrity, might exert a protective effect during ischaemic stroke. METHODS AND RESULTS: Using a murine transient ischaemic stroke model, treatment with recombinant ANGPTL4 led to significantly decreased infarct size and improved behaviour. Quantitative characteristics of the vascular network (density and branchpoints) were preserved in ANGPTL4-treated mice. Integrity of tight and adherens junctions was also quantified and ANGPTL4-treated mice displayed increased VE-cadherin and claudin-5-positive areas. Brain oedema was thus significantly decreased in ANGPTL4-treated mice. In accordance, vascular damage and infarct severity were increased in angptl4-deficient mice thus providing genetic evidence that ANGPTL4 preserves brain tissue from ischaemia-induced alterations. Altogether, these data show that ANGPTL4 protects not only the global vascular network, but also interendothelial junctions and controls both deleterious inflammatory response and oedema. Mechanistically, ANGPTL4 counteracted VEGF signalling and thereby diminished Src-signalling downstream from VEGFR2. This led to decreased VEGFR2-VE-cadherin complex disruption, increased stability of junctions and thus increased endothelial cell barrier integrity of the cerebral microcirculation. In addition, ANGPTL4 prevented neuronal loss in the ischaemic area. CONCLUSION: These results, therefore, show ANGPTL4 counteracts the loss of vascular integrity in ischaemic stroke, by restricting Src kinase signalling downstream from VEGFR2. ANGPTL4 treatment thus reduces oedema, infarct size, neuronal loss, and improves mice behaviour. These results suggest that ANGPTL4 constitutes a relevant target for vasculoprotection and cerebral protection during stroke

Analysis of circulating hem-endothelial marker RNA levels in preterm infants

<p>Abstract</p> <p>Background</p> <p>Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications.</p> <p>Methods</p> <p>Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (<it>AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1</it>) in association with characteristics of prematurity and preterm morbidity.</p> <p>Results</p> <p>Circulating <it>Tie-2 </it>and <it>SCL/Tal1 </it>RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated <it>Tie-2 </it>levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations.</p> <p>Conclusion</p> <p>These preliminary findings suggest that circulating RNA levels especially <it>Tie2 </it>and <it>SCL </it>decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.</p

Hydrocephalus and racemose cysticercosis: surgical alternative by endoscopic third ventriculostomy

International audienc

Occlusions aiguës du tronc basilaire : résultats et pronostic à l’ère de la thrombectomie

International audienceIntroductionAcute basilar artery occlusions represent 20 % of acute ischemic strokes and are associated with a poor outcome. Mechanical thrombectomy is nowadays the reference therapy for large vessel occlusion strokes of the anterior circulation, combined with intravenous thrombolysis and is also indicated in basilar artery occlusion, despite of the lack of recommandations.Recent findingsAccording to the recent literature data, successful recanalization (mTICI 2b-3) is achieved in 79 % of cases, without statistical difference according to the technique (stent retriver vs contact aspiration). However, the reperfusion quality is better (mTICI 3) and faster for primary contact aspiration. Recanalization failure is independantly associated with a worse clinical outcome. Age ≥60 years, NIHSS ≥13 at admission, no prior use of intravenous thrombolysis, angioplasty/stenting, prior antithrombotic therapy and a low pc-ASPECTS were significantely associated with the 90-day mortality.SummaryRecanalization is the main goal to achieve early in acute managment of basilar artery occlusion. Recent endovascular techniques demonstrated their efficiency in particular for contact aspiration technique, and the further randomized pc-ASTER trial will evaluate this strategy compared to the stent-retriever thrombectomy in basilar artery occlusions. However, the 90-day mortality still exceeds 40 %.Les occlusions du tronc basilaire, représentent 20 % des accidents vasculaires ischémiques cérébraux et sont de mauvais pronostic. La thrombectomie mécanique, traitement de référence pour les occlusions proximales de la circulation antérieure est également indiquée dans ce type d’occlusion malgré l’absence de consensus.Données récentesSelon les données récentes de la littérature, une recanalisation satisfaisante est obtenue dans 79 % des cas sans différence significative selon la technique employée. La reperfusion semble meilleure et plus rapide en cas d’aspiration première. L’échec de recanalisation est indépendamment associé à une évolution clinique défavorable. La mortalité à 3 mois est associé à l’âge ≥60 ans, un score NIHSS ≥13 à l’admission, l’absence de thrombolyse intraveineuse, l’angioplastie et/ou stenting et un score pc-ASPECTS bas.ConclusionLa recanalisation efficace est l’objectif premier de la prise en charge initiale, et les techniques endovasculaires récentes ont démontré leur efficacité angiographique avec une supériorité pour l’aspiration distale. Cependant, la mortalité de ces patients dépasse encore les 40 % malgré les dernières avancées techniques

Impact of thrombolysis in acute ischaemic stroke without occlusion: an observational comparative study.

The impact of intravenous recombinant tissue plasminogen activator (IV-rtPA) in patients with acute ischaemic stroke (AIS) but no arterial occlusion is currently a matter of debate. This study aimed to assess functional outcome of such patients with respect to IV-rtPA use. A retrospective case-control analysis was performed comparing the outcome of AIS patients without arterial occlusion with or without IV-rtPA use. Patients were selected from prospective consecutive observational registries of five European university hospitals. The primary study outcome was excellent outcome at 3 months after stroke, as defined by a modified Rankin Scale (mRS) 0-1. A total of 488 patients without arterial occlusion documented by angiography were included in the present study; 300 received IV-rtPA and 188 did not. No between-group difference was found for excellent outcome before and after adjustment for baseline characteristics (adjusted odds ratio for no IV-rtPA use 0.79, 95% confidence interval 0.51-1.24, P = 0.31). Similar results were found for favourable outcome (defined as a 90-day mRS of 0-2) whereas a higher rate of early neurological improvement was found in IV-rtPA-treated patients (adjusted odds ratio 1.99; 95% confidence interval 1.29-3.07, P = 0.002). Sensitivity analyses yielded similar results. Our study suggests that AIS patients without visible arterial occlusion treated with IV-rtPA may have no better outcome at 3 months than those untreated. However, only a randomized controlled trial would provide a definitive answer about the impact of rtPA in acute stroke patients without occlusion. Until then, these patients should be treated by rtPA as recommended