Salvianolic Acid A Protects the Kidney against Oxidative Stress by Activating the Akt/GSK-3/Nrf2 Signaling Pathway and Inhibiting the NF-B Signaling Pathway in 5/6 Nephrectomized Rats.

Salvianolic acid A (SAA) is a bioactive polyphenol extracted from Bunge, which possesses a variety of pharmacological activities. In our previous study, we have demonstrated that SAA effectively attenuates kidney injury and inflammation in an established animal model of 5/6 nephrectomized (5/6Nx) rats. However, there has been limited research regarding the antioxidative effects of SAA on chronic kidney disease (CKD).

Salvianolic acid A attenuates kidney injury and inflammation by inhibiting NF-κB and p38 MAPK signaling pathways in 5/6 nephrectomized rats.

Salvianolic acid A (SAA) is a minor phenolic carboxylic acid extracted from Salviae miltiorrhizae Bunge (Danshen). SAA exhibits a variety of pharmacological activities, such as antioxidative, anti-thrombotic, neuroprotective, and anti-fibrotic effects, as well as protection from myocardial ischemia and prevention of diabetes and other diseases. Furthermore, SAA has shown renal-protective effects in doxorubicin-induced nephropathy.

NS1619 regulates the expression of caveolin-1 protein in a time-dependent manner via ROS/PI3K/PKB/FoxO1 signaling pathway in brain tumor microvascular endothelial cells.

NS1619, a calcium-activated potassium channel (Kca channel) activator, can selectively and time-dependently accelerate the formation of transport vesicles in both the brain tumor capillary endothelium and tumor cells within 15min of treatment and then increase the permeability of the blood-brain tumor barrier (BTB). However, the mechanism involved is still under investigation. Using a rat brain glioma (C6) model, the expression of caveolin-1, FoxO1 and p-FoxO1 protein were examined at different time points after intracarotid infusion of NS1619 at a dose of 30μg/kg/min.

Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway.

Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we first examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. Compared to MS treatment for 0 min group, the protein expression levels of occludin and claudin-5 in brain tumor tissue of rats showed no changes within 1 h and began to decrease significantly after 2 h of MS infusion.

Curcumin ameliorates the permeability of the blood-brain barrier during hypoxia by upregulating heme oxygenase-1 expression in brain microvascular endothelial cells.

Curcumin (Cur) is a major active component of the food flavor turmeric isolated from the powdered dry rhizome of Curcuma longa Linn., which has been used in traditional Chinese medicine to ameliorate intracerebral ischemic damage and reduce brain edema. However, the effects of Cur on the disruption of the blood-brain barrier (BBB) induced by brain ischemia are still unclear.

Role of ROS/RhoA/PI3K/PKB signaling in NS1619-mediated blood-tumor barrier permeability increase.

The calcium-activated potassium channel (K (Ca) channel) activator, NS1619, has been shown to selectively and time-dependently increase the permeability of the blood-tumor barrier (BTB) by downregulating the expression of tight junction (TJ) protein. However, the role of signaling cascades in this process has not been precisely elucidated. This study was performed to determine the role of signaling cascades involving reactive oxygen species (ROS)/RhoA/PI3K/PKB in increasing the permeability of the BTB induced by NS1619.

The protective mechanism for the blood-brain barrier induced by aminoguanidine in surgical brain injury in rats.

This study was performed to investigate the mechanism of blood-brain barrier (BBB) permeability change, which was induced by aminoguanidine (AG) after surgical brain injury (SBI) in rats. Compared to control group, AG (150 mg/kg, i.p.

Calcium-activated potassium channel activator down-regulated the expression of tight junction protein in brain tumor model in rats.

This study was performed to investigate the mechanism of the blood-brain tumor-barrier (BTB) permeability increase, which was induced by NS1619, a selective K(Ca) channel activator. Using a rat brain glioma (C6) model, we exam the expression of ZO-1 and occludin in mRNA and protein level at different time point after intracarotid infusion of NS1619 (30 μg/kg/min) to tumor sites via RT-PCR and Western blot analysis. The mRNA and protein expression of ZO-1 and occludin had no great change before infusion and began to decrease significantly after 2 h NS1619 infusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG).

Adenosine 5'-triphosphate-sensitive potassium channel activator induces the up-regulation of caveolin-1 expression in a rat brain tumor model.

This study was performed to determine whether minoxidil sulfate (MS), a selective Adenosine 5'-triphosphate-sensitive potassium channel (K (ATP) channel) activator, has an effect on the expression of caveolin-1 in the rat's brain tumor tissue. Using a rat brain glioma (C6) model, we found that the expression of caveolin-1 protein at tumor sites was greatly increased after intracarotid infusion of MS at a dose of 30 μg/kg/min for 15, 30, and 60 min via Western blot analysis. And the peak value of the caveolin-1 expression was observed in rats with glioma after 15 min of MS perfusion, which was significantly attenuated by reactive oxygen species (ROS) scavenger (N-2-mercaptopropionyl glycine, MPG).

Dexamethasone enhances calcium-activated potassium channel expression in blood-brain tumor barrier in a rat brain tumor model.

This study was performed to determine whether dexamethasone (DEX) had an effect on calcium-activated potassium channels (KCa channels) in blood-brain tumor barrier (BTB).Using a rat brain glioma model, we found that the expression of KCa channels protein was significantly increased in brain tumor tissue. And bradykinin-induced increase of KCa channels protein was further enhanced after DEX pretreatment for 3 days.

Temporary loss of perivascular aquaporin-4 in white matter after the spinal cord ischemic injury of rats.

The study was performed to investigate whether the ischemic gray matter and white matter show distinct patterns of aquaporin-4 (AQP4) expression in the reperfusion phase using an in-vivo transient spinal cord ischemia model in rats. We investigated to the time course of AQP4 expression at the blood-spinal cord interface by the quantitative immunogold and western blots methods. The results showed that disruption of AQP4 anchoring at the perivascular membrane did not lead to a net loss of protein.

The molecular mechanism of dexamethasone-mediated effect on the blood-brain tumor barrier permeability in a rat brain tumor model.

This study was performed to determine whether dexamethasone (DEX) had an effect on calcium-activated potassium channels (K(Ca) channels) and Occludin protein in blood-brain tumor barrier (BTB). Using a rat brain glioma model, we found that the expression of K(Ca) channels protein and Occludin protein was significantly increased in brain tumor tissue after DEX treatment for 3 days. Compared with non-DEX-treated animals, Evans Blue levels were greatly attenuated in DEX-treated animals.

Bradykinin-induced blood-tumor barrier opening is mediated by tumor necrosis factor-alpha.

Bradykinin has been shown to increase the permeability of blood-tumor barrier (BTB) selectively. This study was performed to determine whether tumor necrosis factor-alpha (TNF-alpha) was involved in the regulation of this biological process. We found that the levels of TNF-alpha mRNA and heat shock factor-1 (HSF1) protein in C6 cells were markedly up-regulated by bradykinin via real-time RT-PCR and Western blot methods.

Bradykinin preconditioning modulates aquaporin-4 expression after spinal cord ischemic injury in rats.

The study investigated whether bradykinin (BK) preconditioning could regulate the expression of aquaporin-4 (AQP4) using an in vivo transient spinal cord ischemia model in rats. BK was infused continuously via the left femoral artery with infusion pump for 15 min (10 microg/kg/min) then we induced ischemia for 20 min and reperfusion for 24 and 72 h respectively. The results demonstrated that the central part of the white matter exhibited loss of perivascular AQP4 and showed a partial recovery toward 72 h of reperfusion.

Role of aminoguanidine in brain protection in surgical brain injury in rat.

The study investigated the effect of aminoguanidine (AG) on surgical brain injury (SBI) in rat. AG (75, 150 and 300 mg/kg, i.p.

Bradykinin preconditioning induces protective effects on the spinal cord ischemic injury of rats.

The study was performed to investigate the effects of bradykinin preconditioning on spinal cord ischemic injury using an in vivo transient spinal cord ischemia model in rats. Prior to ischemia, bradykinin was infused continuously via the left femoral artery starting 15min before ischemia. Neurological functions were evaluated for 7 days postoperatively using modified Tarlov's scores.

Dexamethasone enhances adenosine 5'-triphosphate-sensitive potassium channel expression in the blood-brain tumor barrier in a rat brain tumor model.

This study was performed to determine whether dexamethasone (DEX) had an effect on ATP-sensitive potassium channels (K(ATP) channels) in blood-brain tumor barrier (BTB). Using a rat brain glioma model, we found that DEX could significantly increase the expression of K(ATP) channels protein at tumor sites. And bradykinin-induced increase of K(ATP) channels protein was further enhanced after DEX pretreatment for 3 consecutive days via Western blots and immunohistochemistry methods.

Bradykinin-induced blood-brain tumor barrier permeability increase is mediated by adenosine 5'-triphosphate-sensitive potassium channel.

Bradykinin has been shown to selectively transiently increase the permeability of the blood-brain barrier (BBB). This study was performed to determine whether ATP-sensitive potassium (K(ATP)) channels mediate the increase in permeability of brain tumor microvessels induced by BK. Using a rat brain glioma (C6) model, we found increased expression of K(ATP) channels at tumor sites via Western blot analysis, after intracarotid infusion of bradykinin at a dose of 10 microg/kg/min for 15 min.

Dexamethasone treatment modulates aquaporin-4 expression after intracerebral hemorrhage in rats.

This study investigated whether dexamethasone (DEX) treatment could regulate the expression of aquaporin-4 (AQP4) in rats with intracerebral hemorrhage (ICH). The results demonstrated that DEX significantly reduced AQP4 mRNA level in the perihematomal area compared with control group, but it increased the level in the brain area surrounding the third ventricle at day 1 post-ICH. There was no difference in AQP4 protein levels between DEX group and control group at the two above-mentioned brain regions at day 1 after ICH.