Hypoxic/aglycemic stress alters blood-brain barrier transport systems

Abstract

Increased cerebrovascular permeability is an important factor responsible for the development of ischemic brain injury and edema formation associated with stroke pathophysiology. Extensive studies of stroke research have centered primarily on the response of neurons and astrocytes to hypoxic or ischemic insult. The response of cerebral capillary endothelial cells to hypoxia is not well understood. Damage to the blood-brain barrier (BBB) induced by hypoxia/ aglycemia may influence BBB permeability and transport mechanisms, thereby contributing to the development and severity of stroke. The development of a low flow in situ brain perfusion model was used in this study to illustrate the effect of ischemia/hypoperfusion coupled with hypoxia and aglycemia on BBB transport mechanisms. Three transport markers were used in various combinations of low flow, hypoxia, and aglycemia to characterize BBB transport mechanisms. The results of this study suggest BBB basal permeability is not com promised during low flow perfusion, however in the presence of hypoxia/ aglycemia, a significant change in BBB permeability is observed among the three transport markers. Thus, the effects of ischemia as produced by low flow, hypoxia, and aglycemia alter BBB permeability due to the probable impaired action of many transport systems under these adverse conditions.