Attenuation of ischemic brain edema and cerebrovascular injury after ischemic preconditioning in the rat

Ischemic preconditioning (IPC) induces neuroprotection to subsequent severe ischemia, but its effect on the cerebrovasculature has not been studied ex tensively. This study evaluated the effects of LPC on brain edema formation and endothelial cell damage that follows subsequent permanent focal cerebr al ischemia in the rat. Transient (15 minute) middle cerebral artery occlus ion (MCAO) was used for IPC. Three days after IPC or a sham operation, perm anent MCAO was induced. Twenty-four hours after permanent MCAO, neurologic deficit, infarction volume, and water and ion content were evaluated. Six h ours post-ischemia, blood-brain barrier (BBB) permeability was examined usi ng [H-3]-inulin. Water, ion contents, and BBB permeability were assessed in three zones (core, intermediate, and outer) depending on their relation to the MCA territory. Heat shock protein 70 (HSP70) was also examined as a po tential marker of vascular injury. The model of IPC significantly reduced b rain infarction and neurologic deficit. Compared with a sham operation, IPC also significantly attenuated brain edema formation in the intermediate (s ham and IPC water contents: 5.99 +/- 0.65 vs. 4.99 +/- 0.81 g/g dry weight; P < 0.01) and outer zones (5.02 +/- 0.48 vs. 4.37 +/- 0.42 gig dry weight; P < 0.01) of the ipsilateral hemisphere but not in the core zone. Blood-br ain barrier disruption assessed by [H-3]-inulin was significantly attenuate d in the IPC group and the number of blood vessels that displayed HSP70 imm unoreactivity was also reduced. Thus, IPC significantly attenuates ischemic brain edema formation, BBB disruption, and, as assessed by HSP70, vascular injury. Understanding the mechanisms involved in IPC may provide insight i nto methods for preserving cerebrovascular function during ischemia.