Blood-brain barrier (BBB) leakage plays a key role in
cerebral ischemia-
reperfusion injury. It is quite necessary to further explore the characteristic and mechanism of BBB leakage during
stroke. We induced a focal
cerebral ischemia model by transient
middle cerebral artery occlusion in male rats for defining the time course of BBB permeability within 120 h following reperfusion and evaluate the specific role of tight junction (TJ) associated
proteins claudin-5,
occludin, and ZO-1 as well as
protein kinase C delta (PKCδ) pathway in BBB leakage induced by
reperfusion injury. We verified a bimodal increase in the permeability of the BBB following focal
ischemia by
Evans blue assay. Two peaks of BBB permeability appeared at 3 h and 72 h of reperfusion after 2 h focal
ischemia, respectively. The leak at the endothelial cell was represented at the level of transmission electron microscopy. TTC staining results showed increased
infarct size with time after
cerebral ischemia reperfusion. The
mRNA and
protein expression levels of these three TJ associated
proteins were significantly decreased compared with the
sham-operated group within 120 h of reperfusion, corresponding to the time-dependent change of the biphasic pattern in BBB leakage. The redistribution of
claudin-5,
occludin, and ZO-1 in
ischemia brain microvascular endothelial cells was observed at the same time points. In addition, Western blot assay revealed PKCδ level was also significantly increased in a similar biphasic pattern to above results within 120 h after
cerebral ischemia-reperfusion. This study demonstrates the timing of TJ associated
proteins claudin-5,
occludin, and ZO-1 in light of BBB permeability associated with
cerebral ischemia reperfusion, and suggests PKCδ pathway may participate in TJ barrier open and BBB leakage during
reperfusion injury in a time-dependent manner.