Brain ischemia is well known for its ability to compromise the function of the blood-brain barrier. We assessed blood-brain barrier integrity by examining the leakage of horseradish peroxidase (HRP) and different fragments of amyloid precursor protein from the vascular network into hippocampal parenchyma in rats exposed to brain ischemia with long-term survival. The areas of blood-brain barrier leakage were associated with increased staining of HRP and C-terminal of amyloid precursor protein/beta-amyloid peptide in perivascular space suggesting, respectively, an additional response to ischemia and neuronal death. These results suggest that the events associated with delayed neuronal death in hippocampus compromise blood-brain barrier function. Additionally, these data suggest that the leakage of cytotoxic amyloid precursor protein parts in the CA1 and other sectors of hippocampus may play a role in the development of creepy delayed neuronal death after the ischemia-reperfusion injury. These findings also suggest that the blood-brain barrier vessels along the hippocampal fissure especially in the medial part of the hippocampus are more vulnerable to ischemic episodes than those in other hippocampal areas.