Composition and Organization of Acute Ischemic Stroke Thrombus: A Wealth of Information for Future Thrombolytic Strategies.

peer reviewedDuring the last decade, significant progress has been made in understanding thrombus composition and organization in the setting of acute ischemic stroke (AIS). In particular, thrombus organization is now described as highly heterogeneous but with 2 preserved characteristics: the presence of (1) two distinct main types of areas in the core-red blood cell (RBC)-rich and platelet-rich areas in variable proportions in each thrombus-and (2) an external shell surrounding the core composed exclusively of platelet-rich areas. In contrast to RBC-rich areas, platelet-rich areas are highly complex and are mainly responsible for the thrombolysis resistance of these thrombi for the following reasons: the presence of platelet-derived fibrinolysis inhibitors in large amounts, modifications of the fibrin network structure resistant to the tissue plasminogen activator (tPA)-induced fibrinolysis, and the presence of non-fibrin extracellular components, such as von Willebrand factor (vWF) multimers and neutrophil extracellular traps. From these studies, new therapeutic avenues are in development to increase the fibrinolytic efficacy of intravenous (IV) tPA-based therapy or to target non-fibrin thrombus components, such as platelet aggregates, vWF multimers, or the extracellular DNA network

Intravenous Administration of Human Adipose Derived-Mesenchymal Stem Cells Is Not Efficient in Diabetic or Hypertensive Mice Subjected to Focal Cerebral Ischemia

Copyright © 2019 Mangin, Cogo, Moisan, Bonnin, Maïer and Kubis.As the second cause of death and cognitive decline in industrialized countries, stroke is a major burden for society. Vascular risks factors such as hypertension and diabetes are involved in most stroke patients, aggravate stroke severity, but are still poorly taken into account in preclinical studies. Microangiopathy and sustained inflammation are exacerbated, likely explaining the severity of stroke in those patients. We sought to demonstrate that intravenous administration of human adipose derived-mesenchymal stem cells (hADMSC) that have immunomodulatory properties, could accelerate sensorimotor recovery, prevent long-term spatial memory impairment and promote neurogenesis, in diabetic or hypertensive mice, subjected to permanent middle cerebral artery occlusion (pMCAo). Diabetic (streptozotocin IP) or hypertensive (L-NAME in drinking water) male C57Bl6 mice subjected to pMCAo, were treated by hADMSC (500,000 cells IV) 2 days after cerebral ischemia induction. Infarct volume, neurogenesis, microglial/macrophage density, T-lymphocytes density, astrocytes density, and vessel density were monitored 7 days after cells injection and at 6 weeks. Neurological sensorimotor deficit and spatial memory were assessed until 6 weeks post-stroke. Whatever the vascular risk factor, hADMSC showed no effect on functional sensorimotor recovery or cognitive decline prevention at short or long-term assessment, nor significantly modified neurogenesis, microglial/macrophage, T-lymphocytes, astrocytes, and vessel density. This work is part of a European program (H2020, RESSTORE). We discuss the discrepancy of our results with those obtained in rats and the optimal cell injection time frame, source and type of cells according to the species stroke model. A comprehensive understanding of the mechanisms preventing recovery should help for successful clinical translation, but first could allow identifying good and bad responders to cell therapy in stroke.The RESSTORE project received funding from the European Union’s Horizon 2020 Research and Innovation Programme under the Grant Agreement No. 681044 RESSTORE project (www.resstore.eu) and GM was directly funded by the RESSTORE project

La Maladie d'Alzheimer (étude de la place du médecin généraliste dans la prise en charge du patient Alzheimer en ville)

L'augmentation du nombre de patients atteints de la maladie d'Alzheimer pose de plus en plus de difficultés en terme de prise en charge médico-sociale du patient et de sa famille. Le médecin généraliste est souvent seul au centre d'une prise en charge qui se doit d'être de plus en plus multidisciplinaire. A partir d'une enquête auprès de médecins traitants de patients Alzheimer nous avons cherché à illustrer un exemple de prise en charge en ville avec ses limites et ses attentes. Cette prise en charge était basée sur un suivi gériatrique hospitalier semestriel intégré dans un programme national de recherche. Il apparaît que les principales difficultés de cette prise en charge viennent de leur disponibilité limitée, de la difficulté à organiser un maintien à domicile avec les paramédicaux, de leur manque de temps pour soutenir l'aidant principal et une formation médicale parfois insuffisante. Une implication de plus en plus importante des médecins généralistes dans les réseaux de soins gériatriques paraît inéluctable dans le futur, visant ainsi une prise en charge optimale de ces patients.ST QUENTIN EN YVELINES-BU (782972101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

LES PLANTES SEDATIVES DANS LE TRAITEMENT DE L'INSOMNIE

CLERMONT FD-BCIU-Santé (631132104) / SudocLYON1-BU Santé (693882101) / SudocSudocFranceF

L'organisation hospitalière pour la prise en charge de patients victimes de toxiques de guerre en temps de paix

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Anaesthesia and haemodynamic management of acute ischaemic stroke patients before, during and after endovascular therapy

International audienceEndovascular therapy (EVT) is now standard of care for eligible patients with acute ischaemic stroke caused by large vessel occlusion in the anterior circulation. EVT can be performed with general anaesthesia (GA) or with monitored anaesthesia care, involving local anaesthesia with or without conscious sedation (LA/CS). Controversies remain regarding the optimal choice of anaesthetic strategy and observational studies suggested poorer functional outcome and higher mortality in patients treated under GA, essentially because of its haemodynamic consequences and the delay to put patients under GA. However, these studies are limited by selection bias, the most severe patients being more likely to receive GA and recent randomised trials and meta-analysis showed that protocol-based GA compared with LA/CS is significantly associated with less disability at 3 months. Unlike for intravenous thrombolysis, few data exist to guide management of blood pressure (BP) before and during EVT, but arterial hypotension should be avoided as long as the occlusion persists. BP targets following EVT should probably be adapted to the degree of recanalisation and the extent of ischaemia. Lower BP levels may be warranted to prevent reperfusion injuries even if prospective haemodynamic management evaluations after EVT are lacking

Increased serum QUIN/KYNA is a reliable biomarker of post-stroke cognitive decline

International audienceBackground: Strokes are becoming less severe due to increased numbers of intensive care units and improved treatments. As patients survive longer, post-stroke cognitive impairment (PSCI) has become a major health public issue. Diabetes has been identified as an independent predictive factor for PSCI. Here, we characterized a clinically relevant mouse model of PSCI, induced by permanent cerebral artery occlusion in diabetic mice, and investigated whether a reliable biomarker of PSCI may emerge from the kynurenine pathway which has been linked to inflammatory processes.Methods: Cortical infarct was induced by permanent middle cerebral artery occlusion in male diabetic mice (streptozotocin IP). Six weeks later, cognitive assessment was performed using the Barnes maze, hippocampi long-term potentiation using microelectrodes array recordings, and neuronal death, white matter rarefaction and microglia/macrophages density assessed in both hemispheres using imunohistochemistry. Brain and serum metabolites of the kynurenin pathway were measured using HPLC and mass fragmentography. At last, these same metabolites were measured in the patient's serum, at the acute phase of stroke, to determine if they could predict PSCI 3 months later.Results: We found long-term spatial memory was impaired in diabetic mice 6 weeks after stroke induction. Synaptic plasticity was completely suppressed in both hippocampi along with increased neuronal death, white matter rarefaction in both striatum, and increased microglial/macrophage density in the ipsilateral hemisphere. Brain and serum quinolinic acid concentrations and quinolinic acid over kynurenic acid ratios were significantly increased compared to control, diabetic and non-diabetic ischemic mice, where PSCI was absent. These putative serum biomarkers were strongly correlated with degradation of long-term memory, neuronal death, microglia/macrophage infiltration and white matter rarefaction. Moreover, we identified these same serum biomarkers as potential predictors of PSCI in a pilot study of stroke patients.Conclusions: we have established and characterized a new model of PSCI, functionally and structurally, and we have shown that the QUIN/KYNA ratio could be used as a surrogate biomarker of PSCI, which may now be tested in large prospective studies of stroke patients