Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is...Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.展开更多
Objective To investigate the rule of the aquaporin 4 (AQP4) expression in acute ischemic brain edema, and to study the correlation between AQP4 expression and diffusion weighted imaging (DWI) Methods Thirty ...Objective To investigate the rule of the aquaporin 4 (AQP4) expression in acute ischemic brain edema, and to study the correlation between AQP4 expression and diffusion weighted imaging (DWI) Methods Thirty six Wistar rats were divided into 2 groups randomly, control group (n=12) and operation group (n=24) in which right middle cerebral artery of each animal had been occluded unilaterally (MCAO) at interval times of: 15 minutes, 30 minutes, 1 hours, 3 hours, 6 hours and 24 hours, respectively The operation process of the control group was the same as the operation group except for the MCAO All groups were examined using DWI The apparent diffusion coefficient (ADC), relative density (rd) and relative area (rs) of the biggest hyperintensity signal layer on DWI were measured After that the animals were sacrificed and perfused with the mixture solution consisting of TTC The biggest layers of the ischemic cerebral tissues in each rat corresponding to the DWI were stained with TTC and examined with immunochemistry (△S) , in situ hybridization (α) and histology Results There was no significant change in the control group In the operation group, a hyperintensity signal was found in the DWI of the right MAC territory at 15 minutes after MCAO The ADC value decreased quickly within one hour after MCAO, while the AQP4 expression, rd DWI and rs DWI increased rapidly during this stage As time progressed, the ADC value decreased further to (2 1±0 6)×10 4 mm 2/s at 3 hours, and then began to increase slowly till 24 hours But the AQP4 expression (△S and α) and rd as well as the rs continuously increased slowly between 1 hour and 6 hours after MCAO, followed a peak after 6 hours The AQP4 expression (α) showed a positive relationship with the rs DWI, they all presented two peaks and a plateau The corresponding sequential pathologic changes were a gradual increase of intracellular edema (within one hour), then an emergence of vasogenic edema (1-6 hours), and fin展开更多
Background Previous studies have indicated that thrombi n (TM) may play a major role in brain edema after intracerebral hemorrhages (ICHs). However, the mechanism of TM-induced brain edema is poorly understood. In th...Background Previous studies have indicated that thrombi n (TM) may play a major role in brain edema after intracerebral hemorrhages (ICHs). However, the mechanism of TM-induced brain edema is poorly understood. In this study, we explored the effect of TM on the permeability of the blood brain barrier (BBB) and investigated its possible mechanism, aiming at providing a potential target for brain edema therapy after ICHs.Methods TM or TM + cathepsin G (CATG) was stereotaxically injected into the right caudate nucleus of Sprague-Dawley rats in vivo. BBB permeability was measured by Evans-Blue extravasation. Brain water content was determined by the dry-wet weight method. Brain microvascular endothelial cells were then cultured in vitro. After TM or TM+CATG was added to the endothelial cell medium, changes in the morphology of cells were dynamically observed by phase-contrast light microscopy, and the expression of matrix metalloproteinase-2 (MMP-2) protein was measured by immunohistochemical method.Results BBB permeability increased at 6 hours after a TM injection into the ipsilateral caudate nucleus (P<0.05), peaked between 24 hours (P<0.01) and 48 hours (P<0.05) after the injection, and then declined. Brain water content changed in parallel with the changes in BBB permeability. However, at all time points, BBB permeability and brain water content after a TM+CATG injection were not significantly different from the respective parameters in the control group (P>0.05). TM induced endothelial cell contraction in vitro in a time-dependent manner and enhanced the expression of MMP-2 protein. After incubation with TM+CATG, cell morphology and MMP-2 expression did not change significantly as compared to the control group (P>0.05).Conclusions Increased BBB permeability may be one of the mechanisms behind TM-induced cerebral edema. TM induces endothelial cell contraction and promotes MMP-2 expression by activating protease activated receptor-1 (PAR-1), possibly leading to the opening of the BBB.展开更多
The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (M...The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.展开更多
文摘Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
基金theNationalNaturalScienceFoundationofChina (No 3 0 0 70 2 47)
文摘Objective To investigate the rule of the aquaporin 4 (AQP4) expression in acute ischemic brain edema, and to study the correlation between AQP4 expression and diffusion weighted imaging (DWI) Methods Thirty six Wistar rats were divided into 2 groups randomly, control group (n=12) and operation group (n=24) in which right middle cerebral artery of each animal had been occluded unilaterally (MCAO) at interval times of: 15 minutes, 30 minutes, 1 hours, 3 hours, 6 hours and 24 hours, respectively The operation process of the control group was the same as the operation group except for the MCAO All groups were examined using DWI The apparent diffusion coefficient (ADC), relative density (rd) and relative area (rs) of the biggest hyperintensity signal layer on DWI were measured After that the animals were sacrificed and perfused with the mixture solution consisting of TTC The biggest layers of the ischemic cerebral tissues in each rat corresponding to the DWI were stained with TTC and examined with immunochemistry (△S) , in situ hybridization (α) and histology Results There was no significant change in the control group In the operation group, a hyperintensity signal was found in the DWI of the right MAC territory at 15 minutes after MCAO The ADC value decreased quickly within one hour after MCAO, while the AQP4 expression, rd DWI and rs DWI increased rapidly during this stage As time progressed, the ADC value decreased further to (2 1±0 6)×10 4 mm 2/s at 3 hours, and then began to increase slowly till 24 hours But the AQP4 expression (△S and α) and rd as well as the rs continuously increased slowly between 1 hour and 6 hours after MCAO, followed a peak after 6 hours The AQP4 expression (α) showed a positive relationship with the rs DWI, they all presented two peaks and a plateau The corresponding sequential pathologic changes were a gradual increase of intracellular edema (within one hour), then an emergence of vasogenic edema (1-6 hours), and fin
文摘Background Previous studies have indicated that thrombi n (TM) may play a major role in brain edema after intracerebral hemorrhages (ICHs). However, the mechanism of TM-induced brain edema is poorly understood. In this study, we explored the effect of TM on the permeability of the blood brain barrier (BBB) and investigated its possible mechanism, aiming at providing a potential target for brain edema therapy after ICHs.Methods TM or TM + cathepsin G (CATG) was stereotaxically injected into the right caudate nucleus of Sprague-Dawley rats in vivo. BBB permeability was measured by Evans-Blue extravasation. Brain water content was determined by the dry-wet weight method. Brain microvascular endothelial cells were then cultured in vitro. After TM or TM+CATG was added to the endothelial cell medium, changes in the morphology of cells were dynamically observed by phase-contrast light microscopy, and the expression of matrix metalloproteinase-2 (MMP-2) protein was measured by immunohistochemical method.Results BBB permeability increased at 6 hours after a TM injection into the ipsilateral caudate nucleus (P<0.05), peaked between 24 hours (P<0.01) and 48 hours (P<0.05) after the injection, and then declined. Brain water content changed in parallel with the changes in BBB permeability. However, at all time points, BBB permeability and brain water content after a TM+CATG injection were not significantly different from the respective parameters in the control group (P>0.05). TM induced endothelial cell contraction in vitro in a time-dependent manner and enhanced the expression of MMP-2 protein. After incubation with TM+CATG, cell morphology and MMP-2 expression did not change significantly as compared to the control group (P>0.05).Conclusions Increased BBB permeability may be one of the mechanisms behind TM-induced cerebral edema. TM induces endothelial cell contraction and promotes MMP-2 expression by activating protease activated receptor-1 (PAR-1), possibly leading to the opening of the BBB.
文摘The present study evaluated the effect of dl-3-n-butylphthalide(NBP) ,a novel brain protective agent, on brain edema in rats following focal ischemia. Edema was induced by occluding the right middle cerebral artery (MCAO).producing permanent focal ischemia in the right cerebral hemisphere,which developed ip-silateral brain edema reproducibly. Edema was assessed 24 h after MCA occlusion by determining the brain water content from wet and dry weight measurements,and the sodium,potassium concentrations with ion-selective electrodes. In this model,NBP at the dose of 80,160 and 240 mg/kg po 15 min after MCAO prevented from brain edema in a dose-dependent manner. A significant reduction of sodium content and an increase in potassium level were observed in all drug-treated groups. It showed that NBP strongly attenuated brain water entry,sodium accumulation and potassium loss. Nimodipine treatment(5mg/kg sc) also reduced brain edema (P<0. 05). The results suggest that a strong anti-edema activity of NBP may play an important role to contribute to the treatment of ischemic damage.
