| OBJECTIVE: Brain edema is a serious histopathological response associated with brain ischemia reperfusion injury. The increased intracranial pressure (ICP) and heniation are severe sequelae, which potentially aggravate the neurological outcome , even leading to death. Brain edema is principally composed of cytotoxic and vasogenic edema, and both appear during brain ishchemia reperfusion injury. The former is considered to occur in early brain swelling resulting from ischemia due to the failure of the ionic pump which normally maintains celluar homeostasis. The latter attributes to the blood-brain barrier (BBB) breakdown: fluid escapes from the intravascular to the extravascular and extracelluar space. The failure of BBB does not only faciliate brain edema, but also increase the risk of cerebral hemorrhage. Therefore it is important to protect BBB during brain ishchemai reperfusion injury.Aquaporin 4 is one member of water channel membrane protein family, which involves in water bi-direction transmembrane transport in CNS. It located in the brain-blood and brain-CSF interfaces, including astrocyte endfeet around blood vessels , microvascular endothelial cells and ependymal cells. Accumulating evidence suggest that AQP4 is related to the formation and resolution of brain edema. Toinvestigate the changes of blood-brain barrier (BBB) permeability and AQP4 expression after the focal brain ischemia reperfusion injury in rats, immunohistochemistry is used to detect IgG exudation, which reflect the BBB permeability, and the AQP4 expression in different time after reperfusion injury.METHODS: Healthy male Sprague-Dawley rats, weighing 230-280 g, were randomly assigned to sham-operated group (n=6), ischemia reperfusion group (n=24), which was further averagely divided into 4 subgroups according to the duration of reperfusion injury: 6 h, 2 4h, 4 8h and 7 d. The transient focal ischemia reperfusion injury was induced by introducing a silicone-coated monofilament nylon suture (diameter 0.28 mm) from the right external carotid artery (ECA) to the origin of the MCA . The filament was removed after 90 min to allow reperfusion. The animals evaluated the neurological deficit score were killed at 6 h, 24 h, 48 h, 72h and 7d after reperfusion setout. Then the brains were removed and sliced. Immunohistological staining was used to detect IgG exudation , which reflected the BBB damage degree, and AQP4 expressionRESULTS: 1. The neurological deficit symptoms appeared significantly after the rats suffered from the brain ischemia reperfusion injury. It showed an aggravated trend during the 6 h～48 h after reperfusion injury. However, the neurological symptoms started to alleviate at 72 h and restored at 7d. 2. It was not until 24h after reperfusion that IgG exudation was significant (P<0.05). The peak of IgG exudation appeared at 48h after injury. After then IgG exudation started to decrease. 3. The AQP4 expression in the border of the lesion did not increase significantly at 6 h ischemia reperfusion injury until 24 h (P<0.05). At 24 h after reperfusion it appeared significantly upregulated,.Then it remained such trend until 7 d after injury. 4. There was significantly positive correlation between BBB permeability and the AQP4 expression after the brain ischemia reperfusion injury in rats (r= 0.771, P<0.01 ).CONCLUSION: The upregulated AQP4 expression correlated tightly with the increased BBB permeability, and both are involved in the formation of edema induced by brain ischemia reperfusion in rats. |
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