H2020Индивидуална стипендия2016–2018

PANDORA · Platelets: at the nexus of brain aneurysm

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2016-12-01 → 2018-11-30
Финансиране от ЕС: 173 076 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Тромбоцитите и тяхната роля при развитието на мозъчни аневризми се анализират, за да се разбере как тези клетки влияят върху възпалението и образуването на съсиреци. Това е важно, за да се открият безопасни и неинвазивни методи за превенция на разкъсване на съдовете.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Platelets: at the nexus of brain aneurysm

In the European Union, 15 million people have an unruptured intracranial aneurysm (IA) that may rupture one day and lead to subarachnoid hemorrhage (SAH). The IA rupture event is ominous and lingers as a clinical quandary. No safe and effective non-invasive therapies have, as of yet, been identified and implemented in clinical practice mainly because of a lack of knowledge of the underlying mechanisms. Preventive treatment of IA before rupture is therefore needed. Surgical clipping and endovascular therapy are invasive procedures with potentially serious complications Increasing evidence points to inflammation as one of the leading factors in the pathogenesis of IA. Intrasaccular clot formation is a common feature of IA occurring unruptured and ruptured IA. In addition to forming clots, activated platelets support leukocyte recruitment. Interestingly, platelets also prevent local hemorrhage in inflammatory situations independently of their ability to form a platelet plug. We hypothesize that the role of platelet may evolve throughout the development of IA: initially playing a protective role of in the maintenance of vascular integrity in response to inflammation and contributing later to intrasaccular thrombus formation. What are the platelet signaling pathways and responses involved and to what extent do they contribute to the disease and the rupture event?

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Intracranial aneurysms (IA) with and without subarachnoid haemorrhage (SAH) linger as a potentially devastating clinical problem. Current therapeutic options are limited to invasive therapies, namely microsurgical clipping and endovascular treatment, both of which carry a significant risk of procedural morbidity. Increasing evidence points to inflammation as one of the leading factors in the pathogenesis of IA. Intrasaccular thrombus formation is a common feature of intracranial aneurysm occurring in 25% of unruptured and 70% of ruptured IA. In addition to forming clots, activated platelets support leukocyterecruitment. This cross-talk is a common feature in thrombo-inflammatory vascular disease. Despite these deleterious aspects of platelets, they also prevent local hemorrhage in inflammatory situations independently of their ability to form a platelet plug. The pathophysiological evolution of IA events seems driven by complex cellular interactions between different cell types including platelets, leukocytes and vascular cells (endothelial cells, smooth muscle cells). We hypothesize that the role of platelet roles may evolve throughout the development of IA: initially playing a protective role of in the maintenance of the blood brain barrier in response to inflammation and contributing later to intrasaccular thrombus formation. Therefore, altered platelet function may result in a loss of protection against vascular inflammatory insults. The main objective of this proposal is to better understand and decipher platelet mechanisms during IA formation and rupture. In this current application, we will (i) define platelet activation mechanisms in the development of IA and the impact on the blood-brain barrier integrity, (ii) test efficient anti-platelet therapies in the development and rupture of IA, (iii) define an efficient therapeutic window to intervene on platelet activation (prevention or intervention).

Оригинален текст от CORDIS (на английски).

Участници

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE · ParisКоординаторФранция