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Objective: The goal of this study was to investigate the protective effect of recombinant human EPO(rhEPO) on cerebral microvascular endothelial cells and the mechanisms by which rhEPO interacts with TJs proteins, claudin-5, Occludin and ZO-1 during the early period following traumatic brain injury. Research design: Rats (n = 81) were randomly divided into sham-operated group, TBI group and rhEPO+TBI group. Traumatic brain injury was induced by the Marmarou method. Methods and procedures: Rats were killed at 3, 24, 72 and 168 hours after TBI. The integrity of the blood–brain barrier was investigated by using a spectrophotometer to assess extravasation of Evans blue dye. The expression of Claudin-5, Occludin and ZO-1 were determined by immunohistochemistry and real-time fluorescence quantitative PCR. Results: From 3 hours to 3 days, rats in the TBI group demonstrated a remarkable increase in Evans blue content in the brain, relative to rats in the sham-operated group (p < 0.05). The expression of Claudin-5 and Occludin was significantly lower than those in the sham-operated group (p < 0.05). In contrast, rats in the TBI+rhEPO group demonstrated a significant decrease in brain levels. Conclusion: It was found that administration of rhEPO protected cerebral microvascular endothelial cells and reduced permeability of BBB and the mechanisms may be due to increasing the expression of TJs proteins. [ABSTRACT FROM AUTHOR]

Primary objective: Lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB) in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying disruption of the BBB in LPS-induced sepsis. Research design: Both in vitro and in vivo experiments were designed to test the role of AMP-activated protein kinase (AMPK) in LPS-induced BBB dysfunction. Methods and procedures: Human brain microvascular endothelial cells (HBMECs) were cultured. The protein expressions were detected by western blot. BBB integrity was determined by Evans Blue. Main outcomes and results: LPS (1 μg ml-1) dramatically increased the permeability of the BBB and the ROS productions, as well as reducing the expression levels of occludin and claudin-5 in cultured HBMECs. Inhibition of NAD(P)H oxidase by apocynin or up-regulation of AMPK reversed the LPS-induced abnormities in HBMECs. In LPS-induced sepsis in mice, it was found that LPS dramatically increased NAD(P)H oxidase protein expressions and ROS productions in the brain and disrupted BBB function assayed by Evans blue staining, which were abolished by AICAR treatment. Conclusions: It is concluded that AMPK activation improves the functions of the BBB impaired by LPS through suppression of NAD(P)H oxidase-derived ROS in mice. [ABSTRACT FROM AUTHOR]

Primary objective: This study was designed to evaluate the effect of hypobaric hypoxia (HH) on the function and expression of P2X receptors in rat hippocampus CA1 pyramidal cells. Research design: The functional changes of P2X receptors were investigated through the cell HH model and the expressional alterations of P2X receptors were observed through the animal HH model. Methods and procedure: P2X receptors mediated currents were recorded from the freshly dissociated CA1 pyramidal cells of 7--day--old SD rats by whole cell patch clamp recording. The expression and distribution of P2X receptors were observed through immunohistochemistry and western blot at HH 3--day and 7--day. Main outcomes and results: In acute HH conditions, the amplitudes of ATP evoked peak currents were decreased compared to control. The immunohistochemistry and western blot results reflected there was no change in P2X receptors expression after 3 days HH injury, while P2X receptors expression was up--regulated in response to 7 days HH injury. Conclusions: These findings supported the possibility that the function of P2X receptors was sensitive to HH damage and long--term function decrease should result in the expression increase of P2X receptors. [ABSTRACT FROM AUTHOR]

Background: Neural stem cell treatment and neurogenesis stimulation have gained attention as potential treatments for vascular dementia (VD). Currently, research mainly focuses on neurogenesis occurring in the sub-ventricular zone and dentate gyrus, while the research of the piriform cortex (Pir) is limited. Few results showed that weak neurogenesis exists in the Pir of adult rats. Since neurogenesis occurs in the Pir and is closely related to cognitive function, this study addressed the question of whether neurogenesis occurs in the Pir of an animal with the VD. Primary objective and hypothesis: This study investigated the effects of hyperbaric oxygen therapy on brain blood supply and neurogenesis in the piriform cortex (Pir) of rats with VD. Main outcomes and results: Compared to non-VD control rats (NC), rats with VD showed reduced rCBF, increased rCBV and slower MTT in the Pir. However, following hyperbaric oxygen (HBO) treatment in VD rats, rCBF increased, rCBV decreased and MTT increased. To determine whether the restoration in brain blood supply was associated with increased neurogenesis, immunohistochemical detection of nestin and doublecortin (DCX) was used. In the Pir of both normal and VD rats, nestin positive cells were localized to layer II (superficial cellular layer) and layer III (deep cellular layer). Nestin expression was increased in Pir cells in VD rats and was even more intensely expressed after the HBO treatment. DCX positive cells were mostly located in layer II from amygdaline fissure to rhinal fissure. Conclusion: These results suggest that HBO therapy can improve the blood supply and promote the neurogenesis in the Pir of adult rats with the VD. [ABSTRACT FROM AUTHOR]