OBJECTIVE:Few studies have reported the direct effect of C-X-C motif chemokine ligand 10 (CXCL10) and Neuregulin 1 (Nrg1) on neurons after spinal cord injury (SCI). This study reports the role of CXCL10 in the regulation of neuronal damage after SCI and the potential therapeutic effect of Nrg1. METHODS:The expression level of CXCL10 and Nrg1 in SCI mice was analyzed in the Gene Expression Omnibus DataSets, followed by immunohistochemical confirmation using a mouse SCI model. HT22 cells and NSC34 cells were treated with CXCL10 and Nrg1, individually or in combination, and then assayed for cell viability. The percentage of wound closure was determined through the cell scratch injury model using HT22 and NSC34 cells. Potential molecular mechanisms were also tested in response to either the individual administration of CXCL10 and Nrg1 or a mixture of both molecules. RESULTS:CXCL10 expression was significantly increased in both young and old mice subjected to SCI, while Nrg1 expression was significantly decreased. CXCL10 induced a decrease in cell viability, which was partially reversed by Nrg1. CXCL10 failed to inhibit scratch healing in HT22 and NSC34 cells, while Nrg1 promoted scratch healing. At the molecular level, CXCL10-activated cleaved caspase 9 and cleaved caspase 3 were both inhibited by Nrg1 through pERK1/2 signaling in HT22 and NSC34 cells. CONCLUSIONS:CXCL10 is upregulated in SCI. Despite the negative effect on cell viability, CXCL10 failed to inhibit the scratch healing of HT22 and NSC34 cells. Nrg1 may protect neurons by partially antagonizing the effect of CXCL10.

Post-operative cognitive dysfunction (POCD) can be a serious surgical complication, and patients undergoing cardiac procedures are at particular risk for POCD. This study examined the effect of blocking neuroinflammation on behavioral and neurogenic deficits produced in a rat model of cardiopulmonary bypass (CPB). Minocycline, a drug with established anti-inflammatory activity, or saline was administered daily for 30 days post-CPB. Treatment with minocycline reduced the number of activated microglia/macrophages observed in the dentate gyrus of the hippocampus at 6 months post-CPB, consistent with an anti-inflammatory action in this CPB model. Behavioral testing was conducted at 6 months post-CPB utilizing a win-shift task on an 8-arm radial maze. Minocycline-treated animals performed significantly better than saline-treated animals on this task after CPB. In addition, the CPB-induced reduction in adult neurogenesis was attenuated in the minocycline-treated animals. Together, these findings indicate that suppressing neuroinflammation during the early post-surgical phase can limit long-term deficits in both behavioral and neurogenic outcomes after CPB.

OBJECTIVE Surgery can be highly effective for the treatment of medically intractable, neurological disorders, such as drug-resistant focal epilepsy. However, despite its benefits, surgery remains substantially underutilized due to both surgical concerns and nonsurgical impediments. In this work, the authors characterized a noninvasive, nonablative strategy to focally destroy neurons in the brain parenchyma with the goal of limiting collateral damage to nontarget structures, such as axons of passage. METHODS Low-intensity MR-guided focused ultrasound (MRgFUS), together with intravenous microbubbles, was used to open the blood-brain barrier (BBB) in a transient and focal manner in rats. The period of BBB opening was exploited to focally deliver to the brain parenchyma a systemically administered neurotoxin (quinolinic acid) that is well tolerated peripherally and otherwise impermeable to the BBB. RESULTS Focal neuronal loss was observed in targeted areas of BBB opening, including brain regions that are prime objectives for epilepsy surgery. Notably, other structures in the area of neuronal loss, including axons of passage, glial cells, vasculature, and the ventricular wall, were spared with this procedure. CONCLUSIONS These findings identify a noninvasive, nonablative approach capable of disconnecting neural circuitry while limiting the neuropathological consequences that attend other surgical procedures. Moreover, this strategy allows conformal targeting, which could enhance the precision and expand the treatment envelope for treating irregularly shaped surgical objectives located in difficult-to-reach sites. Finally, if this strategy translates to the clinic, the noninvasive nature and specificity of the procedure could positively influence both physician referrals for and patient confidence in surgery for medically intractable neurological disorders.

Amide herbicides are one of the most applied herbicides at present, and their ethylsulfonic acid-converted products (ESA) have long-lasting influences on environment.Therefore, adsorption-oxidative degradation of the ESA by MnO2 was investigated in this study.Influences of initial concentration of the MnO2, initial pH value and simultaneously presented metal ions on the removal efficiency of ESA were discussed.The results showed that the ESA was degraded by MnO2 efficiently in aqueous solutions, and the increase of initial concentration of MnO2 led to an increased ESA remove efficiency.In addition, the efficiency of of ESA removal increased as decreasing pH values, suggesting that the acidic conditions was favorable to the removal of ESA.The simultaneously presented metal ions had inhibitory effect on the removal of ESA with Fe3+ had greater effect than Na+ and Ca2+.

非甾体抗炎药(NSAIDs)萘普生有着广泛的使用,导致其在水环境和水生生物中被广泛检出.为考察萘普生水生环境安全,以斑马鱼胚胎为模型,将其暴露于不同质量浓度的萘普生溶液中,观察各时间点的死亡率、畸形率和孵化率等,并进一步研究了萘普生对幼鱼运动行为的影响.结果表明:萘普生对斑马鱼胚胎具有致死致畸效应,呈明显的时间—质量浓度效应关系.低质量浓度组的萘普生对斑马鱼早期发育没有显著影响,而在高质量浓度下,死亡率增加显著,48 h的心包囊肿率高达85％.与发育毒性不同,低质量浓度实验组在光照和黑暗条件下均能显著刺激了斑马鱼运动,而高质量浓度2 mg/L实验组却没有明显改变其运动活力.

The carotenoid compound trans-sodium crocetinate (TSC) has been shown to increase oxygenation in various tissues, including the brain. Notably, TSC can enhance oxygenation under conditions of reduced blood flow, thus attenuating the depth of an ischemic challenge. This study examined the impact of TSC on neuronal loss in an animal model of intracerebral hemorrhage (ICH). Utilizing a rat model of collagenase injection, TSC was shown to reduce perihematomal cellular loss after ICH, as assessed by Fluoro-Jade B staining in tissue sections. This is the first evidence demonstrating that TSC is capable of limiting hemorrhagic injury to neurons in the brain. The finding supports the concept that TSC may represent a candidate therapeutic for early intervention regardless of whether a stroke is hemorrhagic or ischemic in nature.

INTRODUCTION:Intussusception is a rare disease in adults and poses a challenge to identify and manage. In adults, surgical resection is the preferred treatment since half are due to malignancy. This case reveals an association between highly active antiretroviral therapy (HAART) and intussusception. PRESENTATION OF CASE:A 44 year-old female with history of HIV on highly active antiretroviral therapy (HAART) presented with 3 month history of epigastric pain, nausea, emesis, weight loss, and lactic acidosis. CT of abdomen showed two small bowel intussusceptions and pericolic fat infiltration. A diagnosis of mitochondrial toxicity secondary to HAART medication was made. HAART medication was discontinued with resolution of symptoms. Further work-up to exclude a mechanical cause for her symptoms including colonoscopy, small bowel follow through, esophagogastroduodenoscopy, and repeat CT were performed. All established an absence of malignancy and intussusception. DISCUSSION:Mitochondrial toxicity (MT) is a well-known complication of HAART. A hallmark of MT is lactic acidosis which when untreated can be fatal. Although MT is known to cause gastrointestinal symptoms, intussusception has not been previously reported. In our patient with MT, prolonged usage of HAART medication resulted in severe gastrointestinal symptoms and intussusception mimicking a surgical abdomen. Laparotomy has been recommended on adult patients with intussusceptions because of the high likelihood of identifying a pathologic lesion. The doctrine of adult intussusception is to operate for concern of malignancy. CONCLUSION:Surgeons, gastroenterologist and internist caring for patients on HAART therapy must be aware of the possibility of MT when evaluating HIV patients for possible surgical abdomen.

Trans-sodium crocetinate (TSC) is a novel carotenoid compound capable of enhancing the diffusion of small molecules in aqueous solutions. TSC improves the diffusion of oxygen and glucose, and increases oxygenation in ischemic brain tissue. TSC also dampens the intensity of an ischemic challenge during an ongoing ischemic event. The current study examined the impact of TSC in rat models of ischemic and hemorrhagic stroke. Rat three vessel occlusion (3VO), and combined 3VO and one vessel occlusion (3VO/1VO) models of ischemic stroke were evaluated for structural and behavioral outcomes. The effects of TSC were also tested in a rat model of intracerebral hemorrhage (ICH). Delayed treatment with TSC reduced infarct volume in a rodent model of transient focal ischemia involving either 2 or 6h of ischemia. Neurological outcomes, based on a multi-scale assessment and automated gait analysis, also were improved by TSC treatment. Additionally, TSC reduced edema and hemorrhagic volume in a rat model of ICH. An optimal therapeutic candidate for early intervention in ischemic stroke should be effective when administered on a delayed basis and should not aggravate outcomes associated with hemorrhagic stroke. The current findings demonstrate that delayed TSC treatment improves outcomes in experimental models of both ischemic and hemorrhagic stroke. Together, these findings suggest that TSC may be a safe and beneficial therapeutic modality for early stroke intervention, irrespective of the type of stroke involved.

The goal of our study was to determine if the timing of the tissue plasminogen activator (tPA) administration influenced its effect on blood-brain barrier (BBB) permeability and the subsequent risk of hemorrhagic transformation. Thirty spontaneously hypertensive male rats were subjected to a 90-minute unilateral middle cerebral artery occlusion. Six rats did not receive tPA treatment (vehicle control: Group 0), intravenous tPA was administered immediately after reperfusion (Group 1) or 4h after reperfusion (Group 2). Dynamic contrast enhancement (DCE) and gradient-echo (GRE) MR sequences were used to assess the dynamic evolution of BBB permeability and hemorrhagic transformation changes at the following time points: during occlusion, and 3h, 6h, and 24h post reperfusion. In all groups, BBB permeability values in the ischemic tissue were low during occlusion. In Group 0, BBB permeability values increased at 3h after reperfusion (p=0.007, compared with the values during occlusion), and further at 6h after reperfusion (p=0.004, compared with those at 3h post reperfusion). At 24h post reperfusion, the values decreased to a level relative to but still higher than those during occlusion (p=0.025, compared with the values during occlusion). At 3h after reperfusion, BBB permeability values in the ischemic tissue increased, but to a greater extent in Group 1 than in Group 0 (p=0.034) and Group 2 (p=0.010). At 6h after reperfusion, BBB permeability values in the ischemic tissue increased further in Group 2 than in Group 0 (p=0.006) and Group 1 (p=0.001), while Group 1 exhibited BBB permeability that were still abnormal but less than those observed at 3h (p=0.001). Group 2 tended to have a higher hemorrhage incidence (36.4%, 4/11) than Group 1 (10.0%, 1/10, p=0.311) and Group 0 (0%), and hemorrhages occurred around 6h after reperfusion when BBB permeability values were the highest. Mortality was higher in Group 2 (63.6%, 7/11) than in Group 0 (0%) and Group 1 (10.0%, 1/10, p=0.024). The findings suggest that the timing of tPA administration is of importance for its impact on BBB permeability and subsequent risk of hemorrhagic transformation.

This study aimed at determining the optimal age group for high-intensity focused ultrasound (HIFU) experiments for producing lesions in rats. Younger rats have thinner skulls, allowing for the acoustic waves to propagate easily through the skull without causing burns of the skin and brain surface. Younger rats however, have a smaller brain that can make HIFU focusing in the brain parenchyma challenging because of the focus size. In this study, we conducted transcranial HIFU sonications in rat pups of different ages (from 9 to 43 d) with a 1.5MHz MR compatible transducer. The electric power was selected to always reach a target temperature of at least 50°C in the parenchyma. The thickness of the skull and of the brain parenchyma was measured using T2-weighted MR imaging. Results showed that the thickness of the brain parenchyma increased quickly from P9 to P12, reaching 8.5 mm at P16, and then increasing gradually along with age. The skull thickness increased gradually from P9 to P26, and then more quickly after P30. The ratio between brain parenchyma thickness and skull thickness decreased gradually with age. For the pups at 30 d, the temperature in the brain tissue adjacent to the skull increased to 48.9°C, and those from the rodents older than 33 d reached 60°C or higher, which can produce undesired irreversible damage in this location. We conclude that young rats aged 16-26 d are optimal for experiments producing transcranial HIFU lesions in rats with an intact skull.

Glioblastoma multiforme (GBM) is the most common and lethal form of brain cancer and these tumors are highly resistant to chemo- and radiotherapy. Radioresistance is thought to result from a paucity of molecular oxygen in hypoxic tumor regions, resulting in reduced DNA damage and enhanced cellular defense mechanisms. Efforts to counteract tumor hypoxia during radiotherapy are limited by an attendant increase in the sensitivity of healthy brain tissue to radiation. However, the presence of heightened levels of molecular oxygen during radiotherapy, while conventionally deemed critical for adjuvant oxygen therapy to sensitize hypoxic tumor tissue, might not actually be necessary. We evaluated the concept that pre-treating tumor tissue by transiently elevating tissue oxygenation prior to radiation exposure could increase the efficacy of radiotherapy, even when radiotherapy is administered after the return of tumor tissue oxygen to hypoxic baseline levels. Using nude mice bearing intracranial U87-luciferase xenografts, and in vitro models of tumor hypoxia, the efficacy of oxygen pretreatment for producing radiosensitization was tested. Oxygen-induced radiosensitization of tumor tissue was observed in GBM xenografts, as seen by suppression of tumor growth and increased survival. Additionally, rodent and human glioma cells, and human glioma stem cells, exhibited prolonged enhanced vulnerability to radiation after oxygen pretreatment in vitro, even when radiation was delivered under hypoxic conditions. Over-expression of HIF-1α reduced this radiosensitization, indicating that this effect is mediated, in part, via a change in HIF-1-dependent mechanisms. Importantly, an identical duration of transient hyperoxic exposure does not sensitize normal human astrocytes to radiation in vitro. Taken together, these results indicate that briefly pre-treating tumors with elevated levels of oxygen prior to radiotherapy may represent a means for selectively targeting radiation-resistant hypoxic cancer cells, and could serve as a safe and effective adjuvant to radiation therapy for patients with GBM.

OBJECTIVE To examine the effects of niacin on lysophosphatidylcholine (LPC)-induced intercellular adhesion molecule-1 (ICAM-1), and gained insight to the mechanisms. METHOD Human umbilical vein endothelial cell line was cultured using Medium 200 medium in incubator at 37 °C and 5% CO2 condition.Experimental groups:(1) the negative control group:medium; (2) LPC different time groups:the medium added with 20 µmol/L final concentration of LPC, were cultured for 10 min and 8 h, 24 h; (3) LPC+ p38-mitogen-activated protein kinase (p38MAPK) inhibitor (SB203580) group:the medium added with 10 µmol/L p38MAPK inhibitor (SB203580) was cultured for 1 h, then human umbilical vein endothelial cells (HUVECs) added with the LPC were cultured for 10 min, 8 h and 24 h.(4) LPC+different niacin dose group:after separately adding with 0.25, 0.5, 1 mmol/L niacin, the cells were cultured for 18 h, then HUVECs added with the LPC were cultured for 10 min, 8 h and 24 h. Cell concentration in each group was 5×10(5)/ml, inoculated in 6-well plates, each well 1 ml. Detected by Western blot analysis of pp38MAPK, ICAM-1 protein content, real-time quantitative PCR to detect endothelial cell ICAM-1 mRNA expression, cell immunofluorescence to detect LPC-induced ICAM-1 protein expression. RESULT In LPC 24 h group, the expression of ICAM-1 protein was significantly increased 0.786 ± 0.02, the LPC+niacin group, ICAM-1 protein levels (0.487 ± 0.015) was significantly lower than the LPC 24 h group (P < 0.01), in LPC+SB203580 intervention group, ICAM-1 protein levels (0.461 ± 0.011) was significantly lower than that of the LPC 24 h group (P < 0.01), but did not reach the level of the control group. Adding LPC to culture for 10 min, phosphorylation of p38MAPK (pp38MAPK) reached its peak (0.47 ± 0.02), niacin could reduce the pp38MAPK (0.07 ± 0.02), SB203580 could also reduce its activity (0.11 ± 0.02). Adding LPC to culture for 8 h, ICAM-1 mRNA expression (8.16 ± 0.15) compared with the control group (1.00 ± 0.02) had a significant increase (t = 24.34, P < 0.01). Compared with the LPC 8 h, niacin reduced LPC-induced ICAM-1 mRNA expression (3.85 ± 0.14), and showed a dose-dependent manner (F = 8.06, P < 0.01), while SB203580 could not effectively reduce the ICAM-1 mRNA (8.09 ± 0.11). CONCLUSION Niacin prevented LPC-induced endothelial dysfunction by reducing expression of ICAM-1. These mechanisms appeared to be at least partly mediated by suppression of the pp38MAPK in endothelial cells. These pleiotropic effects of niacin may potentially contribute to the beneficial effects of risk reduction for atherosclerotic disease.

Ischemic neuronal damage is a common feature of occlusive strokes, hemorrhagic strokes, and traumatic brain injury. In addition, ischemia can be an anticipated or unanticipated complication of a variety of surgical procedures. Most therapeutic strategies for managing ischemic injury seek to re-establish blood flow, suppress neural metabolism, and/or limit specific cellular injury cascades. An alternative therapeutic approach is to enhance the delivery of metabolic substrates to ischemic tissue. This strategy is typified by efforts to increase tissue oxygenation by elevating the levels of circulating oxygen. Our studies are examining a complementary approach in which the delivery of metabolic substrates is enhanced by facilitating the diffusion of oxygen and glucose from the vasculature into neural tissue during ischemia. This is achieved by increasing the diffusivity of small molecules in aqueous solutions, such as plasma and interstitial fluid. The carotenoid compound, trans-sodium crocetinate (TSC) is capable of increasing oxygen and glucose diffusivity, and our studies demonstrate that TSC increases cerebral tissue oxygenation in the penumbra of a focal ischemic event. In addition, TSC treatment reduces the volume of cerebral infarction in rodent models of both permanent and temporary focal ischemia. This strategy of "metabolic reflow" thus blunts the metabolic challenge in partially-perfused tissue and reduces ischemic neural injury.

OBJECTIVE:To compare the antifibrotic effect of oxymatrine and captopril in mice with chronic viral myocarditis (CVMC) and determine the possible antifibrotic mechanism of oxymatrine in CVMC. METHODS:Ninety Balb/c mice were randomly divided into normal control group 1 (n = 10), normal control group 2(n = 10) and CVMC model group (n = 70). The mice in CVMC model group were infected with coxsackievirus B(3) (CVB(3)) on days 0, 14 and 28 to establish CVMC model. The volume of CVB(3) suspension was 0.20 ml, 0.25 ml and 0.30 ml, whose 50% tissue culture infection dose was 10(9) respectively. The mice in the normal control group 1 and 2 were given normal saline of volumes equal to those of viral suspension given to the model group at the same time points. Echocardiography and collagen specific picrosirius red staining were performed to evaluate the CVMC model on day 42 for the mice of the normal control group 1 and 8 mice of CVMC model group. The remaining mice in CVMC model group were randomly divided into CVMC control group, captopril group and oxymatrine group on day 42. From then on, the mice in captopril group and oxymatrine group were treated with captopril or oxymatrine at the dose of 100 mg/kg, by gavage once a day for 28 days, and meanwhile the mice in CVMC control group and the normal control group were given equal-volume normal saline by gastric gavage every day, for 28 days successively. All these mice were sacrificed on day 70. Heart tissue slices were stained with collagen specific picrosirius red and the collagen volume fraction (CVF) was calculated with image analysis software. The expressions of AngII and TGF-beta1 were determined by immunohistochemistry and Western blotting. RESULTS:Compared with normal group 1, the left ventricular end-diastolic internal diameters, left ventricular end-systolic internal diameters and heart rates were significantly increased in CVMC model group (P < 0.05, P < 0.01, P < 0.05, respectively), ejection fractions, fractional shortenings and peak velocity of aorta were all significantly decreased in CVMC model group (P < 0.01 for all comparisons), and CVF levels were significantly increased in CVMC group (P < 0.01) on day 42. Compared with normal control group 2, captopril group and oxymatrine group, CVF levels and the expressions of TGF-beta1 were significantly increased in CVMC control group (P < 0.01 for all comparisons) on day 70. The expressions of AngII in CVMC control group were higher than those in normal control group and captopril group (P < 0.01 for all comparisons), but there were no significant difference between oxymatrine group and CVMC control group (P > 0.05) on day 70. CONCLUSION:Oxymatrine can inhibit myocardial fibrosis in CVMC, and the mechanisms of its antifibrotic effects might be related with the down-regulation of TGF-beta1 expression.

Objective To study the dynamic changes of collagen metabolism and MMP-2/TIMP-2 expressions in hearts of diabetic rats. Methods Wistar rots were randomly divided into four groups: 4-week normal controls, 4-week diabetic rats, 12-week normal controls, and 12-week diabetic rats. The diabetic rats were induced by injecting streptozotocin(STZ, 60 mg/kg). The collagen content, serum MMP-2/TIMP-2 levels, cardiac activity, mRNA and protein expressions of MMP-2/TIMP-2 were determined. Results The collagen contents were increased in diabetic rat hearts (P<0.01). The activity, mRNA expression and protein level of MMP-2 were decreased (P<0.01 except P <0.05 in MMP-2 activity between 4-week diabetic rats vs normal controls) while the serum level and mRNA expression of TIMP-2 were increased (P<0. 05, P <0.01) in diabetic hearts. The serum MMP-2 level and cardiac TIMP-2 protein level were slightly increased at 4 weeks (P>0.05) but markedly at 12 weeks (P<0.05, P<0.01) in diabetic rats. The cardiac MMP-2/TIMP-2 content was positively related to the serum MMP-2/TIMP-2 levels (r=0.565, P<0. 01 ;r=0.415, P<0.05) and gene and protein expressions of TIMP-2 (r=0.609, 0.620; P<0.01) while it was negatively related to activity, gene and protein expressions of MMP-2 (r=-0.797, -0.704, -0.613; P<0.01). Conclusion Imbalance of MMP-2/TIMP-2 might participate in the development of diabetic cardiomyopathy. Serum MMP-2/TIMP-2 might be potential markers for early diagnosis of diabetic cardiomyopathy.

OBJECTIVE:The present study was designed to explore the roles of MMP-2/TIMP-2 in cardiac fibrosis and to study the effects of benazepril, an angiotensin-converting enzyme inhibitor (ACEI) on cardiac remodelling in streptozotocin(STZ)-induced diabetic rats.METHODS AND RESULTS:Male Wistar rats were randomly divided into three groups: a normal control group (NC), a diabetes mellitus-untreated group (DM) and a diabetes mellitus benazepril-treated group (DB). Diabetes mellitus was induced in the DM and DB groups by intraperitoneal injection of streptozotocin (60 mg/kg). DB rats were treated with benazepril 10 mg/kg/day for 12 weeks by remedial perfusing of the stomach. In the DM group, compared with the NC group, the gene and protein expression of MMP-2 decreased while the TIMP-2 gene and protein expression increased in heart tissues, along with a markedly cardiac collagen deposition.All the above changes were attenuated by benazepril treatment in the DB group.CONCLUSIONS:The imbalance of MMP-2 and TIMP-2 expressions in heart tissues might participate in interstitial fibrosis in diabetic myocardiopathy. Benazepril may ameliorate cardiac fibrosis partly by regulating the MMP-2/TIMP-2 system.

OBJECTIVE:As an endogenous antioxidant, taurine could retard the development of diabetic cardiovascular complications. Whereas, whether TAU has a protective effect on diabetic vascular endothelium in young patients is still unclear. This study aimed to investigate the protective effect of taurine on early vascular endothelial dysfunction and its possible mechanism by detecting the changes of oxLDL/LOX-1 system in young STZ-induced diabetic rats. Doing so, the authors expect to find an effective approach in clinical practice to the prevention and treatment of diabetic vascular complication.METHOD:Six-week-old rats were divided randomly into normal control (CN group, n=8), diabetes mellitus group (DM group, n=8) and taurine supplement group (DM+TAU group, n=8). Diabetes was induced in the rats by intraperitoneal injection of streptozotocin (STZ, 60 mg/kg) and after the onset of diabetes, the rats in DM+TAU group were given free access to drinking water containing 1% taurine. At the end of 4 weeks, blood glucose, serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), oxidized low density lipoprotein (oxLDL) and sICAM-1 levels were determined, meanwhile LOX-1 and ICAM-1 expression on abdominal aortas were examined by immunostaining, Western blotting and reverse transcription PCR, respectively. The results were quantified by densitometry.RESULT:Compared to normal control, in STZ-induced diabetic rats, the levels of serum TC, TG, LDL, oxLDL and sICAM-1 were all increased (P<0.01 for all), meanwhile LOX-1 and ICAM-1 expression (protein and mRNA) in the endothelium layers of abdominal aortas were also markedly enhanced (P<0.01 for all); while in taurine supplemented rats, the levels of serum TG (0.64+/-0.12 vs. 0.97+/-0.18), TC (0.82+/-0.18 vs. 1.01+/-0.23), oxLDL (3.1+/-0.6 vs. 4.2+/-0.6), sICAM-1 (108.3+/-18.0 vs. 130.7+/-17.4), expression of LOX-1 and ICAM-1 protein (1.02+/-0.19 vs. 2.60+/-0.33, 1.21+/-0.22 vs. 2.98+/-0.31) as well as mRNA (0.45+/-0.09 vs. 0.96+/-0.15, 0.50+/-0.07 vs. 0.87+/-0.16) were all markedly lower than those of untreated diabetic rats (P<0.05 for all). Also, the level of LOX-1 protein expression was positively correlated with levels of serum oxLDL (r=0.922, P=0.001), sICAM-1 (r=0.753, P=0.031) and ICAM-1 expression on abdominal aorta (r=0.849, P=0.008).CONCLUSION:Vascular endothelial dysfunction was present in early stage of young diabetic rats and taurine supplement could protect against this early endothelial dysfunction by its antioxidation to inhibit the role of oxLDL/LOX-1 system in young rats with diabetes mellitus.

Cerebral vasospasm is a major complication of subarachnoid hemorrhage (SAH). This chapter describes a reproducible, low-mortality, and low-cost model of SAH-induced vasospasm in the mouse. Autologous blood is injected into the cisterna magna of adult mice, and the diameters of large cerebral arteries are measured postmortem. Acute (6–12 h) and persistent (1–3 days) phases of vascular narrowing are observed in cerebral arteries. Vascular narrowing is associated with thickening of the vascular wall and corrugation of the internal elastic lamina; these histological findings have been described by Lin and associates.1 A key advantage of this model is the use of a species for which a variety of resources are available, such as a range of genetically-modified animals. This mouse model could therefore assist in identifying and verifying mechanisms contributing to vascular pathology associated with SAH and facilitate the initial screening of candidate therapies for cerebral vasospasm.

OBJECTIVE:The present study was designed to examine the changes of MMP-2/TIMP-2 in the hearts of streptozotocin-induced diabetic rats and gain insight into their roles in extracellular matrix (ECM) remodelling on an experimental animal model of diabetic cardiomyopathy.METHODS AND RESULTS:Sixteen male Wistar rats were randomly divided into two groups: normal control and diabetic rats. Diabetes mellitus was induced in rats by streptozotocin injection. All rats were fed with standard chow and water ad libitum for 4 weeks. At 4 weeks diabetic rats were associated with a lower body weight (BW) and heart weight (HW) but a higher HW/BW. In the diabetic group, serum MMP-2 level had a tendency to increase but not significantly, while serum TIMP-2 significantly increased. Both the activity and expression of MMP-2 weakened in the hearts of diabetic rats. TIMP-2 gene expression in myocardium enhanced significantly. TIMP-2 protein level in diabetic heart was strengthened slightly but not significantly. VG staining showed a marked deposition of collagen in the diabetic group. Multivariate analysis revealed that total collagen content correlated negatively with the activity and gene expression of MMP-2 in the myocardium, and correlated positively with TIMP-1 mRNA expression.CONCLUSIONS:The decrease in MMP-2 activity and expression and increase in TIMP-2 gene expression in the myocardium of diabetic rats may lead to impairment of collagen degradation and contribute to the matrix deposition in diabetic myocardiopathy. The correlation between the serum level and cardiac expression of TIMP-2 in diabetic rats suggested that serum TIMP-2 level may be a viable marker for early diagnosis of diabetic myocardiopathy.

Objective To report a patient with bilateral traumatic carotid cavernous fistulae (TCCF) who was successfully treated with endovascular covered stent deployment. Methods A 58-year-old male patient with severe head injury presented with pulsatile exophthalmos and bruit. The cerebral angiogram revealed bilateral TCCF. The preservation of ICA in bilateral TCCF patient is very important, so we decided to use coverd stents to occlude the fistulae. After receiving antiplatelet drugs for 3 d, the patient underwent bilateral covered stent implantation by endovascular approach under the general anesthesia. Results The bilateral TCCF were successfully treated by endovascular deployment of expandable coronary PTFE-covered stents (Jostent GraftMaster covered stents 3.5 mm×12 mm and 3.5 mm×16 mm) in bilateral ICA. The angiogram immediately after the intervention revealed obliteration of bilateral TCCF and both ICAs were fully patent. The bruit disappeared immediately after covered stent implantation and the chemosis of both eyes disappeared several days later. No complications related with the endovascular therapy were observed. Conclusion Covered stent implantation is an alternative method for TCCF, especially suitable for the patient whose ICA is cannot be preserved by detachable balloon or the patient who cannot tolerate the ICA occlusion.