Blockage Of Blood Flow Research Articles

Nanoparticles to diagnose and treat atherosclerosis

Researchers have developed nanoparticles that localize to arterial plaques and provide a possible new means to diagnose and treat atherosclerosis. Early detection of atherosclerosis is difficult and effective therapies are not available, making the condition a common cause of death worldwide. Plaques that are the hallmark of the disease form when white blood cells called macrophages attract cholesterol and agglomerate in arteries. These buildups can cause heart attacks, and when macrophages die, they can cause plaques to rupture and block blood flow, potentially causing strokes. High-density lipoprotein (HDL, or “good cholesterol”) deters plaque formation by promoting transport of cholesterol from plaques to the liver for excretion. In 2013, Shanta Dhar’s group at the University of Georgia reported the development of synthetic nanoparticles that mimic HDL functionally. In San Diego last week, Dhar and coworkers reported a modified version. The nanoparticles include a sugar-based macrophage-targeting ligan...

Nitric Oxide and Hydrogen Sulfide Regulation of Ischemic Vascular Remodeling.

Blockage or restriction of blood flow through conduit arteries results in tissue ischemia downstream of the disturbed area. Local tissues can adapt to this challenge by stimulating vascular remodeling through angiogenesis and arteriogenesis thereby restoring blood perfusion and removal of wastes. Multiple molecular mechanisms of vascular remodeling during ischemia have been identified and extensively studied. However, therapeutic benefits from these findings and insights are limited due to the complexity of various signaling networks and a lack of understanding central metabolic regulators governing these responses. The gasotransmitters NO and H2 S have emerged as master regulators that influence multiple molecular targets necessary for ischemic vascular remodeling. In this review, we discuss how NO and H2 S are individually regulated under ischemia, what their roles are in angiogenesis and arteriogenesis, and how their interaction controls ischemic vascular remodeling.

Multidetector Computed Tomography Evaluation of Malignant Superior Vena Cava Syndrome

ABSTRACTIntroductionSuperior vena cava syndrome results from the blockage of blood flow through the superior vena cava. It can be a medical emergency if it causes laryngeal or cerebral edema. Hence, prompt diagnosis is of utmost importance.Case reportA 65-year-old male patient came with complaints of progressive dyspnea and cough since 3 weeks. A contrast- enhanced multidetector computed tomography (MDCT) scan was done for the patient, which showed thrombus in the superior vena cava with a rich network of collaterals. The three-dimensional reconstruction was also done to demonstrate the collaterals.ConclusionThe MDCT provides an excellent tool to diagnose and assess the cause of superior vena cava obstruction.How to cite this articleBacker PH, VVP Seetha, Shukla AK, Nagesh R. Multidetector Computed Tomography Evaluation of Malignant Superior Vena Cava Syndrome. J Med Sci 2016;2(3):53-55.

Developing an in situ forming polyphosphate coacervate as a new liquid embolic agent: From experimental design to pilot animal study

A radiopaque temporary liquid embolic agent was synthesized from polyphosphate (PP) coacervates and optimized using a design of experiments approach. Variables studied were: strontium substitution (0–15mol%), barium substitution (0–15mol%), PP concentration and degree of polymerization of the polyphosphate (Dp). The viscosity, radiopacity and cell viability of the resulting coacervates were measured for 60 formulations and response surface modeling was used to determine the optimum coacervate that maximized radiopacity and cell viability. The optimum coacervate made from PP with a large Dp (9.5g NaPP/100mL, 2.2mol% Sr, 9mol% Ba and 3.8mol% Ca) was taken forward to a pilot animal trial. In this rabbit model, PP embolic agent successfully occluded the central auricular artery with promising biocompatibility. Further study is required to optimize the cohesiveness and clinical effectiveness of PP as an in situ setting temporary embolic agent. Statement of significanceThis article describes the development of a new radiopaque temporary liquid embolic agent from the optimization using design of experiments to a pilot animal study. Embolization is a minimally invasive interventional radiology procedure used to block blood flow in a targeted blood vessel. This procedure is used to treat many conditions including: tumors, aneurysms and arteriovenous malformations. Currently, no inherent radiopaque embolic agents are available in the clinic, which would allow for direct imaging of the material during the procedure and follow up treatment.

Role of Red Cells in Thrombosis and Hemostasis

Until recently it has been assumed that red blood cells (RBCs) play mainly a passive role in hemostasis and thrombosis, but now some studies have uncovered several novel roles for them in both of these processes. The best-known effects of RBCs in clotting in vivo are rheological, involving laminar shearing plus aggregation and deformability of RBCs. In addition, RBCs have specific receptors for platelets and fibrin(ogen) that may be involved in thrombosis. Furthermore, in the contraction of blood clots, the trapping of RBCs in the platelet-fibrin network and subsequent physical changes may be important for hemostasis and thrombosis. Contracted blood clots develop a remarkable structure, with a meshwork of fibrin and platelet aggregates on the exterior of the clot and a close-packed, tessellated array of compressed polyhedral RBCs within. The structure and properties of contracted clots vary depending on the relative amounts of platelets, fibrinogen and RBCs and the conditions of clotting. Such close-packed arrays of polyhedral erythrocytes, or polyhedrocytes, have also been observed in human arterial and especially venous thrombi taken from patients. The mechanical nature of this RBC shape change was confirmed by polyhedrocyte formation from the forces of centrifugation of blood without clotting. Many experiments suggest that polyhedrocytes are more prevalent under conditions associated with thrombosis and could be a marker of prothrombotic conditions. Consistent with this hypothesis, RBC membranes have been found to be a major source of exposure of phosphatidylserine, which forms a procoagulant surface to generate thrombin. Platelets (with their cytoskeletal motility proteins) and fibrin(ogen) (as the substrate bridging platelets for contraction) are required to generate the forces necessary to segregate platelets/fibrin from RBCs and to compress these cells into a tightly packed array. Clots formed after puncture of the mouse saphenous vein are composed primarily of polyhedrocytes, suggesting that they may be important in venous hemostasis. Moreover, the permeability of contracted clots is nearly the same as that of the endothelial cell lining, consistent with their functional significance. These results demonstrate how contracted clots form an impermeable barrier important for hemostasis and wound healing and also to restore flow past obstructive thrombi. On the other hand, they also help explain how fibrinolysis is greatly retarded after clots contract, as a result of these striking structural changes. In summary, RBCs may perform a dual role, both helping to stem bleeding but at the same time contributing to thrombosis in a variety of ways, including when the tightly packed array of RBCs in a contracted clot blocks blood flow and resists dissolution. Disclosures No relevant conflicts of interest to declare.

Modified platelet deposition on matrix metalloproteinase 13 digested collagen I

SummaryBackgroundAtherothrombosis underlies acute coronary syndromes, including unstable angina and acute myocardial infarction. Within the unstable plaque, monocytes express collagenolytic matrix metalloproteinases (MMPs), including MMP‐13, which degrades fibrous collagen. Following rupture, vessel wall components including degraded collagen are exposed to circulating platelets. Platelet receptors then mediate the recruitment and activation of platelets to form a thrombus, blocking blood flow and resulting in myocardial infarction and sudden death.ObjectivesHere we aim to provide information on the effects of collagen degradation on platelet adhesion and thrombus formation.MethodsUsing increasing concentrations of MMP‐13, we induced progressive degradation of fibrous and monomeric collagen I, visualized by electrophoresis, and then investigated the capacity of the resulting fragments to support static platelet adhesion and thrombus formation in whole flowing blood.ResultsBoth integrin and glycoprotein VI‐dependent interactions with fibrous collagen underpin high levels of platelet adhesion under both conditions, with little obvious effect of MMP‐13 treatment. Static platelet adhesion to monomeric collagen was strongly α2β1‐dependent regardless of degradation status. Under flow conditions, partially degraded monomeric collagen supported increased thrombus deposition at 10 μg mL −1 MMP‐13, falling close to background when collagen degradation was complete (100 μg mL −1 MMP‐13).ConclusionsNew binding activities come into play after partial digestion of collagen monomers, and net platelet‐reactivity through all axes is abolished as degradation becomes more complete.

Mathematical modeling and simulation of the evolution of plaques in blood vessels

In this paper, a model is developed for the evolution of plaques in arteries, which is one of the main causes for the blockage of blood flow. Plaque rupture and spread of torn-off material may cause closures in the down-stream vessel system and lead to ischemic brain or myocardial infarctions. The model covers the flow of blood and its interaction with the vessel wall. It is based on the assumption that the penetration of monocytes from the blood flow into the vessel wall, and the accumulation of foam cells increasing the volume, are main factors for the growth of plaques. The dynamics of the vessel wall is governed by a deformation gradient, which is given as composition of a purely elastic tensor, and a tensor modeling the biologically caused volume growth. An equation for the evolution of the metric is derived quantifying the changing geometry of the vessel wall. To calculate numerically the solutions of the arising free boundary problem, the model system of partial differential equations is transformed to an ALE (Arbitrary Lagrangian-Eulerian) formulation, where all equations are given in fixed domains. The numerical calculations are using newly developed algorithms for ALE systems. The results of the simulations, obtained for realistic system parameters, are in good qualitative agreement with observations. They demonstrate that the basic modeling assumption can be justified. The increase of stresses in the vessel wall can be computed. Medical treatment tries to prevent critical stress values, which may cause plaque rupture and its consequences.

Sickle Cell Disease

Sickle cell disease affects between 70,000 and 90,000 individuals in the United States, the majority of whom are of African-American descent. The genetic basis of the disease is an abnormality in the β-globin gene, which causes the red blood cells to change to a “sickle” shape due to low oxygenation. The life span of patients with this disease has improved over the past few decades, although morbidity remains high. This review covers the pathophysiology of sickle cell disease and the stabilization and assessment, diagnosis and treatment, maintenance and preventive therapies, and cure of patients with sickle cell disease. Figures show hemoglobin electrophoresis; age at death for individuals with sickle cell disease in the years 1979, 1989, 1999, and 2006; sickled cells blocking blood flow; acute chest syndrome; dactylitis; and avascular necrosis. Tables list important trials, topics in need of further research, common complications, most common intravenous pain medications, and indications for transfusion. This review contains 6 highly rendered figures, 5 tables, 97 references, and a list of educational resources.

Numerical investigation of fluid–particle interactions for embolic stroke

Roughly one-third of all strokes are caused by an embolus traveling to a cerebral artery and blocking blood flow in the brain. The objective of this study is to gain a detailed understanding of the dynamics of embolic particles within arteries. Patient computed tomography image is used to construct a three-dimensional model of the carotid bifurcation. An idealized carotid bifurcation model of same vessel diameters was also constructed for comparison. Blood flow velocities and embolic particle trajectories are resolved using a coupled Euler–Lagrange approach. Blood is modeled as a Newtonian fluid, discretized using the finite volume method, with physiologically appropriate inflow and outflow boundary conditions. The embolus trajectory is modeled using Lagrangian particle equations accounting for embolus interaction with blood as well as vessel wall. Both one- and two-way fluid–particle coupling are considered, the latter being implemented using momentum sources augmented to the discretized flow equations. It was observed that for small-to-moderate particle sizes (relative to vessel diameters), the estimated particle distribution ratio—with and without the inclusion of two-way fluid–particle momentum exchange—were found to be similar. The maximum observed differences in distribution ratio with and without the coupling were found to be higher for the idealized bifurcation model. Additionally, the distribution was found to be reasonably matching the volumetric flow distribution for the idealized model, while a notable deviation from volumetric flow was observed in the anatomical model. It was also observed from an analysis of particle path lines that particle interaction with helical flow, characteristic of anatomical vasculature models, could play a prominent role in transport of embolic particle. The results indicate therefore that flow helicity could be an important hemodynamic indicator for analysis of embolus particle transport. Additionally, in the presence of helical flow, and vessel curvature, inclusion of two-way momentum exchange was found to have a secondary effect for transporting small to moderate embolus particles—and one-way coupling could be used as a reasonable approximation, thereby causing substantial savings in computational resources.

Scintigraphic evaluation of therapeutic angiogenesis induced by VEGF-loaded chitosan nanoparticles in a rodent model of hindlimb ischemia

We examined the therapeutic effect of chitosan nanoparticles (CHI) incorporating vascular endothelial growth factor (VEGF) on hindlimb ischemia using single photon emission computed tomography (SPECT) perfusion imaging. Rats (n=24) were divided randomly into four groups of six: control, VEGF, CHI, and CHI incorporated with VEGF (CHI-VEGF). The right femoral artery was ligated to block blood flow, and SPECT perfusion images were obtained every week for 4 weeks. The morphology of the synthesized CHI was identified as a spherical shape with an even size distribution (range, 93–250 nm). The VEGF loading efficiency in CHI was 8.6±2.1%. Upon injection into the femoral artery, 17.6±8.2% of the 99mTc-labeled CHI-VEGF administered remained in the ischemic lesion. The restoration of blood flow (ratio of ischemia to normal) measured by SPECT perfusion imaging was greater in animals treated with CHI-VEGF compared to that in the control (p=0.028), VEGF (p=0.010), and CHI (p=0.011) groups. Administering CHI-VEGF had a significant therapeutic effect in a hindlimb ischemic rat model. 99mTc gamma perfusion imaging was useful to study therapeutic angiogenesis. Open image in new window

Blood flow reduction of covered small side branches after flow diverter treatment: A computational fluid hemodynamic quantitative analysis

Small side branches related brain infarction remains one of the major concerns for flow-diverter devices. However, among several factors, whether this high-profile stent would significantly block blood flow into small side branches remains unclear. The authors quantitatively evaluate blood flow reduction due to the deployment of flow-diverter devices using computational fluid dynamics approach. Thirty one patient-specific anterior inferior cerebellar artery geometries were employed. The flow-diverter device was hypothetically embedded into the basilar trunk, and to cover the anterior inferior cerebellar arteries. The blood flow reduction of each anterior inferior cerebellar artery following flow-diverter device deployment was calculated, with independent validations for both inflow and outflow conditions. Efficient diameters of the anterior inferior cerebellar arteries were calculated to evaluate any correlation with blood flow reduction after flow-diverter devices.The blood flow reduction ratio was shown to be 3.61±1.94%. There was moreover no significant difference of either inflow or outflow boundary conditions during the simulation. The results were calculated approximately as a modest linear correlation between the blood flow reduction ratio and the size of anterior anterior inferior cerebellar arteries which had a mean efficient diameter of 1.12±0.36mm (range from 0.31mm to 1.91mm), and the R2 was 0.361. When covered by flow-diverter devices, the mechanical blood flow reduction in anterior inferior cerebellar arteries was found to be low with a maximum value estimated to be less than 8%. Therefore, mechanical blood flow reduction is probably not the leading factor contributing to small side branches related brain infarction.

Application of blocking blood flow in laparoscopic opening-taking embryo operation on interstitial tubal pregnancy

Objective To explore the safety and feasibility of blocking blood flow in interstitial tubal pregnancy treated with laparoscopic opening-taking embryo operation. Methods The clinical data of 98 patients with lump interstitial tubal pregnancies (requesting reserve procreate function) from January 2006 to December 2013 were chosen. Among them, 56 patients were in study group (January 2010-December 2013) and 42 patients were in control group (January 2006-December 2009). All patients were treated with opening-taking embryo by laparoscopic operation. In study group, we first blocked the uterine artery and ovarian artery blood supply of pregnancy lump, secondly opened pregnancy lump and stripped gestation sac with hydraulic pressure separation during operation. Whereas, in control group, we opened pregnancy lump and taken out pregnancy tissues according to convention method without blocking blood flow. Operation success rate, operation blood volume, operation time, persistent ectopic pregnancy (PEP) happening rate, fallopian tube unobstructed information, and pregnancy information after operation were compared between two groups. Results In study group, operation success rate was 96.4%, which was significantly higher than that in control group (61.9%) (P<0.01); operation blood volume was[(20.7±10.4)ml], which was significantly less than that in control group [(60.7±18.4)ml](P<0.01); operation time [(46.6±14.2)min] was significantly shorter than that in control group [(66.5±19.4)min](P<0.01); there was no PEP in study group, while there were 5 PEPs (11.9%) in control group. Fallopian tube unobstructed rate after operation in study group (76.9%) was significantly higher than that in control group (41.7%) (P<0.05). Conclusions Application of blocking blood flow in opening-taking embryo by laparoscopic operation on lump interstitial tubal pregnancies is safe and effective. Key words: Fallopian tubes /BS/SU; Pregnancy, tubal /SU; Laparoscopy

Cardiology patient page. Spontaneous coronary artery dissection (SCAD).

The coronary arteries carry oxygen- and nutrient-rich blood to the heart, which allows it to pump and supply blood to the body. The coronary arteries can become blocked by various processes related to cholesterol (atherosclerotic) or other causes (nonatherosclerotic), which can cause heart attacks when the blockages are severe enough to impede blood flow to the heart. Although the atherosclerotic form is most common, nonatherosclerotic blockages (especially dissections/tears) are increasingly recognized as important causes of heart attacks, particularly in women. This article focuses on spontaneous coronary artery dissection (SCAD). SCAD is defined as a tear in the coronary arterial wall that is not related to trauma or medical instrumentation. This spontaneous tear can result from a disruption of the innermost lining of the arterial wall, causing blood to rush in from the lumen (center channel of the artery) into the arterial wall. Alternatively, separation of the arterial walls can occur as a result of bleeding caused by spontaneous rupture of small vessels that feed the arterial wall. The buildup of blood inside the arterial wall compresses the lumen, blocking blood flow to the heart. SCAD is considered to be rare in the general population, although it has been underdiagnosed, and its true prevalence is unknown. Overall, it is an infrequent cause of and accounts for only up to 4% of heart attacks.1 However, SCAD proportionally causes a higher number of heart attacks in young women; ≈25% of women ≤50 years old had heart attacks caused by SCAD in 1 series.2 SCAD affects predominantly women in ≈90% …

Anti-inflammatory effects of vinpocetine in atherosclerosis and ischemic stroke: a review of the literature.

Immune responses play an important role in the pathophysiology of atherosclerosis and ischemic stroke. Atherosclerosis is a common condition that increases the risk of stroke. Hyperlipidemia damages endothelial cells, thus initiating chemokine pathways and the release of inflammatory cytokines—this represents the first step in the inflammatory response to atherosclerosis. Blocking blood flow in the brain leads to ischemic stroke, and deprives neurons of oxygen and energy. Damaged neurons release danger-associated molecular patterns, which promote the activation of innate immune cells and the release of inflammatory cytokines. The nuclear factor κ-light-chain-enhancer of activated B cells κB (NF-κB) pathway plays a key role in the pathogenesis of atherosclerosis and ischemic stroke. Vinpocetine is believed to be a potent anti-inflammatory agent and has been used to treat cerebrovascular disorders. Vinpocetine improves neuronal plasticity and reduces the release of inflammatory cytokines and chemokines from endothelial cells, vascular smooth muscle cells, macrophages, and microglia, by inhibiting the inhibitor of the NF-κB pathway. This review clarifies the anti-inflammatory role of vinpocetine in atherosclerosis and ischemic stroke.

Plasminogen and Plasmin Increase after Polytrauma Shifting the Thrombin/Plasmin Activity Ratio Toward Fibrinolysis

Background: Hemostasis is regulated by a dynamic balance between thrombin and plasmin activity, and the supply of prothrombin and plasminogen in the general circulation. This dynamic balance is important so that the formation of clots occurs at the site of injury, but does not spread to distal sites where thrombus formation can block blood flow and lead to organ dysfunction. Procoagulant and fibrinolytic activity is regulated by the supply of both active enzymes, and their respective zymogens. Disruption in the plasma levels of the enzymes and zymogens can lead to coagulopathies that have serious effects on morbidity and mortality. Polytrauma and hemorrhage can lead to an acute coagulopathy in rats that mimics the clinical hypocoagulation in both civilian and military patients with severe trauma and hemorrhage. This coagulopathy could be due an imbalance between the pro-coagulant or fibrinolytic systems.Hypothesis: We hypothesized that the dynamic balance between thrombin and plasmin activities would be altered after polytrauma and hemorrhage, favoring fibrinolysis.Method: Sprague-Dawley rats (n=8) were anesthetized with Isoflurane. Polytrauma was induced by damage to the small intestines, the left and medial liver lobes, the right leg skeletal muscle, and by fracturing the right femur. Rats were then bled to a mean arterial pressure of 40mmHg and held there until 40% of the blood volume was removed. No fluid resuscitation was given. Blood samples were taken before (time 0) and at 30, 60, 120 and 240min. Rat plasmin and thrombin activity were measured by enzymatic assay. Plasminogen and prothrombin were measured after conversion to their respective active enzymes with tissue plasminogen activator or factor Xa respectively. Active enzyme was subtracted from the total to give the levels of zymogens. D-dimers were measured by ELISA.Results: There was no significant change in plasma thrombin activity after polytrauma and hemorrhage. Prothrombin levels fell slightly, but significantly over time. In contrast, plasmin activity rose significantly by 30min and continued to be elevated through the next 4hrs (235%, p<0.05), and was paralleled by an increase in D-dimers (10±2.6 to 59±16ng/ml, P<0.05). Surprisingly, plasminogen also rose in the first 30min and continued to be significantly elevated by 4hrs paralleling the rise in plasmin (100±2.7 to 119±3.9ug/ml, P<0.05). Prothrombin and plasminogen levels were 40 to 100 times higher than their respective active enzymes at each time point, suggesting that the zymogen pool is not depleted even in this severe trauma model. The thrombin/plasmin activity ratio was calculated and found to fall rapidly 30 min after polytrauma and was low over the next 4hrs.Conclusion: These data suggest that polytrauma and hemorrhage lead to dynamic changes in procoagulant and fibrinolytic systems. There was a rise in plasmin activity, and the fall in the thrombin/plasmin ratio suggesting that the fibrinolytic component dominates over time. The fall in prothrombin suggests consumption of the zymogen. Surprisingly, plasminogen levels rose quickly, suggesting that this acute phase protein is actively secreted after polytrauma. The high levels of prothrombin and plasminogen in comparison to thrombin and plasmin, suggests that the precursor pool for the active enzymes is not depleted. Polytrauma and hemorrhage led to a rapid decrease in the thrombin/plasmin activity ratio and suggests that fibrinolysis is rapidly activated. These results provide mechanistic support to clinical data showing that early treatment with anti-fibrinolytic drugs reduces bleeding. This project was funded by US Army Medical Research and Materiel Command. DisclosuresNo relevant conflicts of interest to declare.

Alain Tedgui: atherosclerosis research à la Française.

Atherosclerosis is a slow-progressing, life-threatening condition in which fatty deposits accumulate in blood vessel walls and develop into thick plaques. Although these early stages of the disease generally progress asymptomatically and can develop over decades, if and when a plaque eventually ruptures, it can cause a thrombus that blocks blood flow and may cause death within minutes. Alain Tedgui Over the last 3 decades, Alain Tedgui, Director of the Paris Cardiovascular Research Center (PARCC), has studied nearly every step of the disease, including how blood pressure and flow influence cell signaling, gene expression, and the deposition of lipids in artery walls,1–4 how inflammatory processes perpetuate the condition,5–8 and how, when plaques rupture, they release thrombogenic microparticles.9,10 In a recent interview with Circulation Research , Tedgui explained that he maintained this wide diversity of research interests by doing science the French way—training excellent scientists, giving them independence, but keeping them close. He also emphasized that maintaining such diversity is the key to keeping an open mind and making the most interesting discoveries. Tedgui is unquestionably a world leader in atherosclerosis research. But surprisingly, he started out with the intention of becoming a mathematician. Quickly realizing his true calling, he managed to turn a PhD in theoretical fluid mechanics into experimental expertise in arterial wall biology, and never looked back. ### Where Did You Grow Up? I grew up in the city of Oran in Algeria, North Africa, which at the time was French. And I left when it became independent in 1962. I was eight-and-a-half years old, and we moved to Paris, France, where my father already had some family. ### Tell Me About Your Family? I am from a Jewish family. I have a younger brother and older sister. I’m in the middle. My father was a carpenter. He left school and started …

Characteristics and outcomes of varied treatment modalities for partially thrombosed intracranial aneurysms: a review of 35 cases

The purpose of this study was to analyze the characteristics of partially thrombosed intracranial aneurysms (PTIAs) in terms of location, shape, size, and symptoms, and to assess outcome according to the type of treatment. We reviewed the radiological and clinical findings of 35 cases of PTIAs followed in our institution between 2006 and 2011. We divided all treatment modalities into two groups. Patients in group A (n = 15) were treated by blood flow blockage from the lesion of the pathogenic segment of the parent where the PTIAs originated, and patients in group B (n = 20) were only treated with obliteration of the remnant perfused aneurysmal sac. Radiological and clinical outcomes of treatment were compared between the two groups. Group A showed complete occlusion in 15 cases (100 %) compared to six cases (30.0 %) in group B (p < 0.001). No cases required retreatment in group A, while six cases (30.0 %) underwent retreatment in group B (p = 0.027). In terms of clinical outcome, 12 cases (80.0 %) showed symptomatic improvement in group A compared to eight cases (40.0 %) in group B (p = 0.037). Nine cases (60.0 %) showed improvement in postoperative GOS at six months compared to initial preoperative GOS in group A versus four (20.0 %) in group B (p = 0.032). PTIAs should be treated by preventing blood flow from the lesion of the pathogenic segment of the parent artery where PTIAs originate. This treatment approach is associated with better clinical and radiological outcomes.

Substrate-mediated delivery of microRNA-145 through a polysorbitol-based osmotically active transporter suppresses smooth muscle cell proliferation: implications for restenosis treatment.

Smooth muscle cells (SMCs) can grow over a stent surface and block blood flow through the stent, resulting in restenosis. MicroRNAs (miRNAs) are post-transcriptional regulators that contribute to cell proliferation, survival, and metabolism. Several miRNAs, including miR-145, have been identified that regulate vascular SMC proliferation and are down-regulated under conditions of proliferation. We hypothesized that SMC proliferation would be reduced or diminished if miR-145 expression was restored in SMCs. We designed a method to coat the stent surface with miR-145 to suppress the over-growth of SMCs. For effective miRNA delivery, various types of nanocarriers were tested for enhanced transfection efficiency and biocompatibility in the case of surface-mediated delivery. Physico-chemical characterization of the prepared nanoparticles was performed, and the cell viabilities and transfection efficiencies of the carriers were studied and compared to select the most efficient carrier for substrate-mediated delivery. The polysorbitol-based osmotically active transporter (PSOAT) retained its transgene delivery capacity and had higher biocompatibility than the other tested carriers. We detected reporter and therapeutic gene expression at the stent surface following PSOAT-mediated delivery. SMC proliferation after the treatment with PSOAT/miR-145 nanoparticles (PMN) was monitored using the MTS assay, and miR-145 target gene expression after PMN treatment was measured by reverse transcription-polymerase chain reaction. PSOAT-mediated delivery of miR-145 was associated with efficient intracellular expression of the therapeutic gene. A drastic reduction in SMC proliferation was observed after PMN treatment, and miR-145 target proteins were down-regulated upon miR-145 replacement.

A Method for Generate a Mouse Model of Stroke: Evaluation of Parameters for Blood Flow, Behavior, and Survival

Stroke is one of the common causes of death and disability. Despite extensive efforts in stroke research, therapeutic options for improving the functional recovery remain limited in clinical practice. Experimental stroke models using genetically modified mice could aid in unraveling the complex pathophysiology triggered by ischemic brain injury. Here, we optimized the procedure for generating mouse stroke model using an intraluminal suture in the middle cerebral artery and verified the blockage of blood flow using indocyanine green coupled with near infra-red radiation. The first week after the ischemic injury was critical for survivability. The survival rate of 11% in mice without any treatment but increased to 60% on administering prophylactic antibiotics. During this period, mice showed severe functional impairment but recovered spontaneously starting from the second week onward. Among the various behavioral tests, the pole tests and neurological severity score tests remained reliable up to 4 weeks after ischemia, whereas the rotarod and corner tests became less sensitive for assessing the severity of ischemic injury with time. Further, loss of body weight was also observed for up 4 weeks after ischemia induction. In conclusion, we have developed an improved approach which allows us to investigate the role of the cell death-related genes in the disease progression using genetically modified mice and to evaluate the modes of action of candidate drugs.

Effect of exogenous apelin-13 on cerebral ischemia-reperfusion injury in rats

Objective To evaluate the effect of exogenous apelin-13 on cerebral ischemia-reperfusion （I/R） injury in rats .Methods Fifty-eight male Sprague-Dawley rats ,aged 6-8 weeks ,weighing 250-320 g ,were randomly divided into 7 groups using a random number table ：sham operation group （group S , n=10 ） ,I/R group （n=10） ,dimethyl sulfoxide group （group D , n=6） ,apelin-13 （1 nmol） ＋ I/R group （group A1 , n=6） , apelin-13 （5 nmol ） ＋ I/R group （group A5 , n=10 ） ,apelin-13 （5 nmol ） ＋ LY294002 （PI3K inhibitor ） group （group A5 ＋LY , n=10） ,and apelin-13 （10 nmol） ＋ I/R group （group A10 , n=6） .Focal cerebral ischemia was produced by introducing a nylon intraluminal suture into the cervical internal carotid artery and advancing it intracranially to block blood flow into the middle cerebral artery according to the method described by Longa et al . The corresponding dose of apelin-13 ,apelin-13＋ LY294002 10 nmol ,or the equal volume of dimethyl sulfoxide was injected into the lateral cerebral ventricle in each group at 30 min before cerebral ischemia .Neurological function was assessed and scored using neurologic behavior scores （NBSs） at 24 and 72 h of reperfusion .The rats were sacrificed at 24 h of reperfusion and brains removed for detection of cell apoptosis and expression of phosphorylated-glycogen synthase kinase 3 beta （pGSK-3β） .The rats were sacrificed at 72 h of reperfusion to measure the cerebral infarct size .Results Compared with S group ,NBSs at each time point were significantly＆nbsp;decreased ,the cerebral infarct size was enlarged ,the number of apoptotic neurons was increased ,and pGSK-3βexpression was up-regulated in group I/R （ P〈0.05 or 0.01） .Compared with I/R group ,NBSs were significantly increased ,and the cerebral infarct size was decreased in A 5 and A10 groups ,and the number of apoptotic neurons was reduced ,and pGSK-3βexpression was up-regulated in group A5 （ P〈0.05） .NBSs were significantly lower , the cerebral infarct size was larger ,and pGSK-3βexpression was lower in A5＋LY group than in A5 group （ P〈0.05） .Conclusion Exogenous Apelin-13 can attenuate cerebral I/R injury in rats and activation of the PI3K signaling pathway and enhanced inactivation of GSK-3βare involved in the mechanism . Key words: Reperfusion injury; Brain; Apelin-13