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.