Coline Grisotto1,2, Janice Taïlé1, Cynthia Planesse1, Nicolas Diotel1, Marie-Paule Gonthier1, Olivier Meilhac1,3, David Couret1,2. 1. Diabète Athérothrombose Thérapies Réunion Océan Indien, INSERM, UMR 1188, Université de La Réunion, 2 rue Maxime Rivière, 97400 Sainte-Clotilde, La Réunion, France. 2. CHU de la Réunion, Service de Neuroréanimation, 97410 Saint-Pierre de la Réunion, La Réunion, France. 3. CHU de la Réunion, 97400 Saint-Denis de la Réunion, La Réunion, France.
Abstract
BACKGROUND: Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. METHODS: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. RESULTS: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30-46.7%) vs. 28.45 (IQR 21-30%); p = 0.016) and HT (HFD: 2 (IQR 1-5) vs. ND: 0 (IQR 0-1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. CONCLUSION: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.
BACKGROUND:Stroke in context of type 2 diabetes (T2D) is associated with a poorer outcome than in non-diabetic conditions. We aimed at creating a new reproducible mouse model of stroke in impaired glucose tolerance conditions induced by high-fat diet. METHODS: Adult C57BL6 mice were fed for 2 months with either normal diet (ND) or high-fat diet (HFD). We used a model of Middle Cerebral Artery Occlusion (MCAO) for 90 min. Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT) were used to assess pre-diabetic status. Brain infarct volume, hemorrhagic transformation (HT) as well as systemic and cerebral inflammatory markers were evaluated. RESULTS: HFD was associated with an increased body weight and glycemia following OGTT. The HFD group presented a significant increase in brain infarct volume (38.7 (IQR 30-46.7%) vs. 28.45 (IQR 21-30%); p = 0.016) and HT (HFD: 2 (IQR 1-5) vs. ND: 0 (IQR 0-1); p = 0.012) and higher levels of IL-6 and MCP-1 in infarcted hemisphere compared to the ND group. CONCLUSION: Two months of HFD in adult mice were sufficient to alter the lipid profile and the control of hyperglycemia. These metabolic perturbations were significantly associated with increased infarct volume and hemorrhagic complications.
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