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Mechanisms and Consequences of Cerebral Oedema on the Prognosis of Spontaneous Intracerebral Haemorrhages

Abstract : Spontaneous intracerebral haemorrhage (ICH) is associated with a dramatic prognosis and remains devoid of specific treatment. Therefore, understanding the mechanisms of ICH pathology and repair is a matter of high priority. The peri-haemorrhagic zone, commonly called "peri-haematomal oedema" (PHE), might be a promising candidate for therapeutic interventions. However, its underlying mechanisms, natural evolution and prognostic value remain to date unclear. This thesis aimed at studying the mechanisms and consequences of this PHE. To do so, we combined an experimental (animal model of ICH) and a neuropathological (post-mortem study on human tissue) approach.We used the double autologous blood injection model to reproduce ICH in a large cohort of male and female rats. In a first study, we showed how multimodal MRI is a reliable tool to track the dynamic progression of peri-haematomal injuries and we characterized the kinetics of different PHE components (water content, [micro]-vessel injuries, neuro-inflammation and iron deposits). In a second study, we investigated the short and long-term consequences of ICH. We reported that a deep ICH provokes long term cognitive impairments in rats that affects both hippocampal and non hippocampal aspects of cognition contrasting with early spontaneous locomotor recovery. We also showed that focal striatal ICH induces distant brain atrophy and hypometabolism involving limbic system structures and cortical areas. We included 19 cases of patients who died from ICH in a post-mortem study. We provided evidence for Neutrophil extracellular Traps (NETs) infiltration within the haematoma core but also and within the PHE. We also investigated the natural kinetic of natural blood clearance process after ICH in human brain tissue with a focus on the monocyte-macrophage scavenger receptor (CD163)/hemoxygenase-1 (HO-1) pathway. Our findings contribute to refine our perception of PHE, to optimize the translational pipeline and, hopefully, to identify innovative therapeutic strategies for ICH.
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Submitted on : Monday, May 30, 2022 - 2:41:11 PM
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Laurent Puy. Mechanisms and Consequences of Cerebral Oedema on the Prognosis of Spontaneous Intracerebral Haemorrhages. Human health and pathology. Université de Lille, 2021. English. ⟨NNT : 2021LILUS058⟩. ⟨tel-03681643⟩

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