DS0407 -

PREVENT THE OCCURRENCE OF DELAYED CEREBRAL ISCHEMIA FOLLOWING SUBARACHNOID HEMORRHAGE – PREDIC

Submission summary

Subarachnoid hemorrhage (SAH) occurs in the setting of a ruptured cerebral aneurysm or arteriovenous malformation (AVM). The socio-economic impact of SAH is important because it affects young subjects with around one third of the survivors who maintain severe neurological aftereffects. SAH leads, in a large number of cases, to the death of patients before their first medical contact. In the remaining cases, the underlying vascular lesion is treated by endovascular or neurosurgical interventions to reduce the risk of re-bleeding. Nevertheless, survivors are prone to complications that include hydrocephalus, re-bleeding, seizures, cardiac dysfunctions and finally delayed cerebral ischemia (DCI). Our knowledge of the mechanisms responsible for post-SAH delayed cerebral ischemia are limited, with no clinical treatment which has show a proven efficacy.

The objective(s) of our proposal are:
1. The development of a reproducible and clinically relevant model of DCI post-SAH in mice.
2. The development of ultrasound-based imaging techniques with an unprecedented spatio and temporal resolution to reveal vascular brain microdamages (microthrombosis, micro-inflammation and vasospams).
3. The exploration of the mechanisms that drive the occurrence of post-SAH DCI.
4. The development and validation of strategies to reduce the occurrence of DCI and of its behavioral impact.

To succeed in meeting these objectives, we will combine our expertise in the field of neurovascular disorders and imaging (Inserm UMR-S U919, GIP Cyceron – D. Vivien) with the use of a set of innovative ultrasonic approaches implemented by the group of M. Tanter (Inserm UMR-S U979, Institut Langevin, ESPCI).

The first expected result is the development of a DCI post-SAH mouse model with comprehensive evaluation including histology, imaging and behavior. This model will improve our knowledge about the pathophysiology of SAH and DCI and will allow us to evaluate different strategies for brain protection post-SAH. Beyond basic research on prevention of delayed ischemia, ultrasonic imaging modalities developed in the framework of our project could be translated in clinics in a very near future. Our innovative techniques could be implemented for conventional radiology. Furthermore, microbubbles used as contrast agents for ultrasound localization microscopy of endothelial adhesion molecules may be further developed for future pre-clinical and clinical applications.

Project coordinator

Monsieur Denis VIVIEN (serine proteases and pathophysiology of the neurovascular unit)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

Inserm UMR-S U919 serine proteases and pathophysiology of the neurovascular unit
Physique des Ondes pour la Médecine

Help of the ANR 546,160 euros
Beginning and duration of the scientific project: September 2016 - 36 Months

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