Effect of Hyperglycemia on Brain Penetrating Arterioles and Cerebral Blood Flow Before and After Ischemia/Reperfusion
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ORIGINAL ARTICLE
Effect of Hyperglycemia on Brain Penetrating Arterioles and Cerebral Blood Flow Before and After Ischemia/Reperfusion Marilyn J. Cipolla & Julie A. Godfrey
Received: 17 November 2009 / Revised: 7 January 2010 / Accepted: 22 January 2010 / Published online: 9 March 2010 # Springer Science+Business Media, LLC 2010
Abstract The effect of preexisiting hyperglycemia on cerebral blood flow (CBF) and brain penetrating arterioles before and after 2 h of ischemia and 30 min of reperfusion was determined. Male Wistar rats that were either hyperglycemic (50 mg/kg streptozotocin; n=24) or normoglycemic (n= 24) were subjected to transient ischemia by filament occlusion or nonischemic. CBF was measured prior to ischemia using microspheres and during transient ischemia using laser Doppler. Edema was compared by wet/dry weights. Constriction to apamin, TRAM-34, and LNNA, inhibitors of small- and intermediate-conductance calcium-activated potassium channels (SK and IK) and nitric oxide, were compared in penetrating arterioles from the ischemic hemisphere to investigate changes in basal tone and endothelium-dependent vasodilator responses. Preexisiting hyperglycemia did not affect CBF in nonischemic animals or after transient ischemia; however, edema was significantly greater. Ischemia and reperfusion caused decreased basal tone in penetrating arterioles similarly in normoglycemic and hyperglycemic animals that was restored by apamin, and further increased by TRAM-34 and L-NNA. The restoration of tone in penetrating arterioles by apamin and TRAM-34 suggests that transient ischemia activates SK and IK channels in penetrating arterioles. This effect of ischemia was not different between normoglycemic and hyperglycemic animals, suggesting that it was related to ischemia and reperfusion rather than hyperglycemia. M. J. Cipolla (*) : J. A. Godfrey Departments of Neurology, Obstetrics, Gynecology & Repro Sciences, and Pharmacology, University of Vermont, 89 Beaumont Ave., Given C454, Burlington, VT 05405, USA e-mail: [email protected]
Keywords Hyperglycemia . Ischemic stroke . Lenticulostriate arterioles . Calcium-activated potassium channels . Cerebral edema
Introduction Hyperglycemia is common in acute stroke, affecting 30– 50% of patients, often without preexisting diabetes [1–4]. Numerous studies have shown that admission hyperglycemia worsens stroke outcome and is an independent risk factor for death and disability following ischemic stroke [4– 9]. The risk of death in nondiabetic hyperglycemic stroke patients is increased 3-fold [9], suggesting that it is hyperglycemia per se and not complications associated with diabetes that contributes to poor outcome in these patients. In animal studies, hyperglycemia has also been shown to aggravate ischemic injury. Preexisting hyperglycemia increases infarction, edema formation, and hemorrhagic transformation during transient ischemia [10–13]. Both metabolic derangements [13] and increased perfusion deficit due to poor reperfusion [10–12] have been shown to contribute
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