Increased mortality after stroke is associated with development of brain edema. The aim of the present study was to examine the contribution of endothelial myosin light chain (MLC) phosphorylation to hypoxia-induced blood-brain barrier (BBB) opening. Measurements of trans-endothelial electrical resistance (TEER) were performed to analyse BBB integrity in an in vitro co-culture model (bovine brain microvascular endothelial cells (BEC) and rat astrocytes). Brain fluid content was analysed in rats after stroke induction using a two-vein occlusion model. Dihydroethidium was used to monitor intracellular generation of reactive oxygen species (ROS) in BEC. MLC phosphorylation was detected using immunohistochemistry and immunoblot analysis. Hypoxia caused a decrease of TEER values by more than 40%, which was prevented by inhibition of the MLC-kinase (ML-7, 10 lmol/L). In addition, ML-7 significantly reduced the brain fluid content in vivo after stroke. The NAD(P)H-oxidase inhibitor apocynin (500 lmol/L) prevented the hypoxia-induced TEER decrease. Hypoxia-dependent ROS generation was completely abolished by apocynin. Furthermore, ML-7 and apocynin blocked hypoxia-dependent phosphorylation of MLC. Our data demonstrate that hypoxia causes a breakdown of the BBB in vitro and in vivo involving ROS and the contractile machinery.

Background and Purpose-Cerebral venous ischemia often induces severe brain edema. Vascular endothelial growth factor (VEGF), which induces angiogenesis, is also known as vascular permeability (VP) factor. The present study was undertaken to investigate whether the inhibition of VEGF could reduce brain edema formation and cerebral venous infarction (CVI) in a rat 2-vein occlusion (2-VO) model. Methods-We used 2-VO model in which 2 adjacent cortical veins were photochemically occluded. Male Wistar rats (nϭ25) were divided into 2 groups: one group was treated with a VEGF antagonist (antagonist group, nϭ10) and the second group was treated with phosphate-buffered solution (PBS) (PBS group, nϭ15). VEGF antagonist or PBS was injected intraperitoneally immediately after 2-VO. The developing ischemic infarct was evaluated by magnetic resonance imaging (MRI) and histology 24 hours after occlusion. Results-VEGF expression was observed in the cytoplasm of neurons exclusively in the area of vasogenic edema that was shown as a high-intensity area in the apparent diffusion coefficient of water map. Ischemic volumes calculated from each MR images, which are related to infarction and/or vasogenic edema, respectively, were significantly smaller in the antagonist group as compared with the PBS group (PϽ0.05) Conclusions-Our study is the first to provide evidence that the inhibition of VEGF attenuates VP and reduces CVI in the acute stage. Although VEGF is a significant angiogenesis factor, we concluded that the inhibition of VEGF might be a new therapy for both brain edema formation and CVI.

Without denying the efficacy of the single-stage surgery, two-stage management can be a reasonable alternative for carefully selected patients who have spinal infection.

After 2-vein occlusion, continuous intraventricular administration of BDNF protected the cerebral cortex against apoptosis and reduced infarct size without affecting rCBF.

Once infection is clinically controlled, a titanium mesh-bone graft composite and plate in combination with aggressive debridement might provide an effective therapy for spinal osteomyelitis requiring surgery. Despite studying a small number of patients, we can conclude that titanium mesh reconstruction can be useful as a surgical method in selected low-risk patients with vertebral osteomyelitis.