Hyperglycemia Induces Progressive Changes in the Cerebral Microvasculature and Blood-brain Barrier Transport during Focal Cerebral Ischemia

Abstract

Hyperglycemia generally enhances cerebral ischemic injury. Most attention on a mechanism has focused on the adverse effect of increased lactate production (acidosis) leading to neuronal injury. The effects of hyperglycemic on another possible primary target, the cerebral microvasculature, is examined in this study. Focal cerebral ischemia was achieved by thread occlusion of the middle cerebral artery (MCA). Preischemic hyperglycemia was induced by intraperitoneal administration of 50% of D-glucose solution. In contrast to normoglycemic controls, glucose-injected rats showed a well demarcated pale infarct after 2 or 4 hours of ischemia reflecting a reduction in cerebral plasma volume (CPV) to 73 ± 9 and 55 ± 6% of contralateral by 2 and 4 hours respectively. Cerebral blood flow (CBF) measured by laser-Doppler flowmetry indicated that after the initial decline in CBF with MCA occlusion, hyperglycemia led to a further progressive reduction during ischemia. Blood-brain barrier transport measured by permeability surface area (PS) product for glutamine was reduced in both normoglycemic and hyperglycemic rats. However, the decline was greater in the hyperglycemic rats. Hyperglycemia induces progressive cerebrovascular changes and affects blood-brain barrier transport during focal cerebral ischemia. These changes may contribute to the adverse effects of hyperglycemia in stroke.