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 extensively. This study evaluated the effects of IPC on brain edema formation and endothelial cell damage that follows subsequent permanent focal cerebral ischemia in the rat. Transient (15 minute) middle cerebral artery occlusion (MCAO) was used for IPC. Three days after IPC or a sham operation, permanent MCAO was induced. Twenty-four hours after permanent MCAO, neurologic deficit, infarction volume, and water and ion content were evaluated. Six hours post-ischemia, blood-brain barrier (BBB) permeability was examined using [3H]-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 potential marker of vascular injury. The model of IPC significantly reduced brain infarction and neurologic deficit. Compared with a sham operation, IPC also significantly attenuated brain edema formation in the intermediate (sham 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 g/g dry weight; P < 0.01) of the ipsilateral hemisphere but not in the core zone. Blood-brain barrier disruption assessed by [3H]-inulin was significantly attenuated in the IPC group and the number of blood vessels that displayed HSP70 immunoreactivity 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 into methods for preserving cerebrovascular function during ischemia.
Masada
T
T
Department of Surgery, University of Michigan, Ann Arbor 48109-0532, USA.
Hua
Y
Y
Xi
G
G
Ennis
S R
SR
Keep
R F
RF
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001812:Blood-Brain Barrier / Q000502:physiology*; D001921:Brain / Q000473:pathology*; D001929:Brain Edema / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D002544:Cerebral Infarction / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D007839:Functional Laterality; D018840:HSP70 Heat-Shock Proteins / Q000032:analysis; D007444:Inulin / Q000493:pharmacokinetics; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D007444:Inulin