A hemorrhagic transformation model of mechanical stroke therapy with acute hyperglycemia in mice |
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Authors: | David Couret Steeve Bourane Aurélie Catan Brice Nativel Cynthia Planesse Anne‐Claire Dorsemans Imade Ait‐Arsa Maxime Cournot Philippe Rondeau Jessica Patche Alexy Tran‐Dinh Gilles Lambert Nicolas Diotel Olivier Meilhac |
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Affiliation: | 1. Université de La Réunion, INSERM, UMR 1188 Diabète Athérothrombose Réunion Océan Indien (DéTROI), Saint‐Denis de La Réunion, France;2. CHU de La Réunion, Service de Neuroréanimation, Saint‐Pierre de La Réunion, France;3. Plateforme CYROI, Cyclotron Réunion Océan Indien, Sainte‐Clotilde, France;4. H?pital Gabriel Martin, Service de Cardiologie, Saint‐Paul de La Réunion, France;5. CHU de La Réunion, Saint‐Denis de La Réunion, France;6. CHU Bichat, INSERM, Paris, France |
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Abstract: | Clinical benefit for mechanical thrombectomy (MT) in stroke was recently demonstrated in multiple large prospective studies. Acute hyperglycemia (HG) is an important risk factor of poor outcome in stroke patients, including those that underwent MT. The aim of this therapy is to achieve a complete reperfusion in a short time, given that reperfusion damage is dependent on the duration of ischemia. Here, we investigated the effects of acute HG in a mouse model of ischemic stroke induced by middle cerebral artery occlusion (MCAO). Hyperglycemic (intraperitoneal [ip] injection of glucose) and control (ip saline injection) 10‐week male C57BL6 mice were subjected to MCAO (30, 90, and 180 min) followed by reperfusion obtained by withdrawal of the monofilament. Infarct volume, hemorrhagic transformation (HT), neutrophil infiltration, and neurological scores were assessed at 24 hr by performing vital staining, ELISA immunofluorescence, and behavioral test, respectively. Glucose injection led to transient HG (blood glucose = 250–390 mg/dL) that significantly increased infarct volume, HT, and worsened neurological outcome. In addition, we report that HG promoted blood‐brain barrier disruption as shown by hemoglobin accumulation in the brain parenchyma and tended to increase neutrophil extravasation within the infarcted area. Acute HG increased neurovascular damage for all MCAO durations tested. HTs were observed as early as 90 min after ischemia under hyperglycemic conditions. This model mimics MT ischemia/reperfusion and allows the exploration of brain injury in hyperglycemic conditions. |
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Keywords: | acute hyperglycemia blood‐brain barrier brain hemorrhagic transformation ischemic stroke neutrophils RRID: AB_303154 RRID: AB_2650996 RRID: AB_2650997 RRID: AB_141359 |
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