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Master Thesis

Effets délétères des n-6 AGPI sur l'ischémie cérébrale retardée après hémorragie sous-arachnoïdienne chez le rat

Abstract : Background and goal of study: Delayed cerebral ischaemia (DCI) [1] is the first cause of morbidity after subarachnoid haemorrhage (SAH). A growing body of evidence suggests that arachidonic acid (AA) metabolism is a driving force behind the patho-physiology of DC. Several eicosanoids were found in the cerebrospinal fluid (CSF) of patients with DCI. These potent vasoconstrictors induce platelet aggregation and mediate inflammation which in turn leads to ischemic brain injury. The aim of our study was first to estimate the occurrence of DCI in a pro-inflammatory state using an high-omega 6 polyunsaturated fatty acids diet (w6) and second to identify eicosanoids underlying this trend. Materials and methods: Sixty rats (400g) were randomly assigned to one of 4 groups: (n=15 per group: a double 250μL intracisternal injection of autologous arterial blood (SAH groups) or artificial CSF (CSF group) was performed. To induce a proinflammatory state animals were fat with w6 during 6 weeks before SAH procedure (SAH_w6). Evaluation of uptakes of 3 [99mTc]­radiolabeled agents was achieved using microSPECT/CT imaging: HMPAO at D5 for cerebral perfusion quantification and AnnexinV at D4 for apoptotic activity study. Brain and plasma were harvested at D6 for further lipidomics analysis. Results and discussion: W6 enriched diet state before SAH dramatically decreased HMPAO uptake compare to SAH group. AnnexinV uptake were also significantly increased in the SAH_w6 group compare to SAH group. w6/w3 plasma ratio was significantly higher in the SAH_w6 group compare to others. Brain concentrations of 8isoPGA2 and LXA4 were higher in the SAH_w6 group compare to SAH group. Conclusion: For the first time, a SAH rat model served to highlight the deleterious role of w6 in the pathophysiology of DCI. Arachidonic-acid-derived eicosanoids seem to be involved through their pleiotropic effects. [1] Vergouwen, M. D. I. et al. Stroke 42, 924–929 (2011)
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David Tonon. Effets délétères des n-6 AGPI sur l'ischémie cérébrale retardée après hémorragie sous-arachnoïdienne chez le rat. Sciences du Vivant [q-bio]. 2017. ⟨dumas-01878057⟩

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