Lysophospholipids transport across blood-brain barrier in an in vitro reconstruction model.

This study builds on our previous study, which highlighted the need for further research on the potential use of lysophospholipid (LPL) supplementation to prevent chronic and age-related diseases. We aimed to evaluate the transmembrane transport of LPL across rat and monkey blood-brain barrier (BBB) models. An in vitro monkey BBB model is required to elucidate the differences between rat and primate BBB-related data and to measure the permeability of LPLs being researched in relation to the human BBB. Based on our previous experiment, porcine liver decomposition product-derived phospholipids (PEL) strongly inhibit α-synuclein (α-Syn) aggregation. We have identified several candidates potentially relevant for the inhibition of α-Syn aggregation, such as LPC18:1, LPE18:1, and LPI18:0; however, the BBB permeability of these LPLs remains unclear. In the present study, we assessed the ability of these LPLs to pass through the in vitro rat and monkey BBB models. LPC18:1 showed high BBB permeability, LPI18:0 showed medium permeability, and the BBB permeation of LPE18:1 was negligible. Our results suggest that LPC18:1 and LPI18:0 are functional food factors that can cross the BBB.

Partially thrombosed giant basilar tip aneurysm that remarkably decreased in size after stent-assisted coiling associated with the disappearance of neovascularization.

Endovascular treatment for partially thrombosed giant basilar tip aneurysms has not been established because of its low cure rate and numerous associated comorbidities. Although some authors reported the growth mechanism of partially thrombosed aneurysm, there is no report for the process of its shrinkage after treatment. We describe a case of a partially thrombosed giant basilar tip aneurysm presenting with disturbance of consciousness because of a mass effect and brain edema. The patient underwent stent-assisted coiling using a low-profile visualized intraluminal support stent (Terumo). Although pre-operative magnetic resonance imaging (MRI) and angiography revealed prominent neovascularization of the inner aneurysmal layer, this vessel was absent on follow-up angiography 1 month after treatment. Repeat angiography demonstrated the gradual recanalization of the aneurysm. However, repeat MRI examinations showed remarkable shrinkage of the thrombosed aneurysm, and the complete disappearance of the thrombosed component was noted 6 months after treatment. The disappearance of neovascularization 1 month after the treatment may have contributed to the shrinkage of the thrombosed aneurysm. Stent-assisted coiling combined with alteration caused a hemodynamic change in this aneurysm, and the flow-diverting effect might have controlled this partially thrombosed giant aneurysm.

Structurally different lysophosphatidylethanolamine species stimulate neurite outgrowth in cultured cortical neurons via distinct G-protein-coupled receptors and signaling cascades.

Neurite outgrowth is important in neuronal circuit formation and functions, and for regeneration of neuronal networks following trauma and disease in the brain. Thus, identification and characterization of the molecules that regulate neurite outgrowth are essential for understanding how brain circuits form and function and for the development of treatment of neurological disorders. In this study, we found that structurally different lysophosphatidylethanolamine (LPE) species, palmitoyl-LPE (16:0 LPE) and stearoyl-LPE (18:0 LPE), stimulate neurite growth in cultured cortical neurons. Interestingly, YM-254890, an inhibitor of Gq/11 protein, inhibited 16:0 LPE-stimulated neurite outgrowth but not 18:0 LPE-stimulated neurite outgrowth. In contrast, pertussis toxin, an inhibitor of Gi/Go proteins, inhibited 18:0 LPE-stimulated neurite outgrowth but not 16:0 LPE-stimulated neurite outgrowth. The effects of protein kinase C inhibitors on neurite outgrowth were also different. In addition, both 16:0 LPE and 18:0 LPE activate mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase 1/2, but the effect of the MAPK inhibitor differed between the 16:0 LPE- and 18:0 LPE-treated cultures. Collectively, the results suggest that the structurally different LPE species, 16:0 LPE and 18:0 LPE stimulate neurite outgrowth through distinct signaling cascades in cultured cortical neurons and that distinct G protein-coupled receptors are involved in these processes.

Population Pharmacokinetics of Teicoplanin and Its Dosing Recommendations for Neutropenic Patients With Augmented Renal Clearance for Hematological Malignancies.

BACKGROUND: Plasma teicoplanin concentrations do not reach the therapeutic range in several patients with hematological malignancies. Nevertheless, the characteristics of the population pharmacokinetic (PPK) models have not been clarified for malignancy. The decrease in the teicoplanin concentration in patients with cancer has been attributed to augmented renal clearance (ARC). It is essential to identify the causative factors of ARC to construct a PPK model to optimize the administration method. The authors aimed to establish a PPK model and develop an appropriate dosing regimen for teicoplanin in patients with hematological malignancies. METHODS: PPK analysis was performed using therapeutic drug monitoring (TDM) data from 119 patients with hematological malignancies. The developed model was verified by predictive performance. RESULTS: The covariates affecting systemic clearance were serum creatinine, presence or absence of neutropenia (<500/µL), and body size descriptor. Patients with hematologic malignancies and neutropenia showed a 25% increase in clearance compared with those with a normal neutrophil count. The PPK model was constructed based on the presence or absence of neutropenia. This model allowed the selection of the most appropriate dosage regimen out of those recommended by the TDM guidelines for patients with eGFR of >60 mL/min/1.73 m2. The PPK model predicted a dosing regimen for achieving a 10% improvement in the coverage probability of the target concentration range during the loading and maintenance phases. CONCLUSIONS: The PPK model may help optimize dose regimens and evaluate dosing methods, using comparative simulations, in patients with hematological malignancies.

Nonbacterial Thrombotic Endocarditis Associated with Acute Promyelocytic Leukemia: An Autopsy Case Report.

Valve vegetation is one of the most fearful findings for physicians. The first diagnosis that comes to their mind is infective endocarditis (IE), but it can also be noninfective; nonbacterial thrombotic endocarditis (NBTE). NBTE can be even more challenging than IE for physicians because of the wide range of differential diagnoses such as malignancies, autoimmune disorders and human immunodeficiency virus. A 45-year-old woman presented at the emergency room with a sudden onset of dysarthria and right-sided hemiplegia. Laboratory data showed her blood counts and coagulation test were mostly normal and the magnetic resonance imaging detected a high-signal-intensity change in her left brain. An echocardiogram found a vegetation-like structure on her atrial valve. We highly suspected IE leading to cerebral embolism. The clot was successfully removed by our neurosurgeons and anticoagulation therapy was started concurrently. Her state of consciousness improved, but then she suffered a brain hemorrhage and died. The autopsy revealed that the cause of her vegetation was acute promyelocytic leukemia (APL). Based on these findings, it is important to remember that APL can be the cause of NBTE even if the blood count and coagulation tests are almost normal.

Utility of systemic voriconazole in equine keratomycosis based on pharmacokinetic-pharmacodynamic analysis of tear fluid following oral administration.

OBJECTIVE: To clarify the detailed pharmacokinetics (PK) of orally administered voriconazole in tear fluid (TF) of horses for evaluating the efficacy of voriconazole secreted into TF against equine keratomycosis. ANIMALS STUDIED: Five healthy Thoroughbred horses. PROCEDURES: Voriconazole was administrated through a nasogastric tube to each horse at a single dose of 4.0 mg/kg. TF and blood samples were collected before and periodically throughout the 24 hours after administration. Voriconazole concentrations in plasma and TF samples were analyzed using liquid chromatography-electrospray tandem-mass spectrometry. The predicted voriconazole concentration in both samples following multiple dosing every 24 hours was simulated by the superposition principle. RESULTS: The mean maximum voriconazole concentrations in plasma and TF were 3.3 µg/mL at 1.5 h and 1.9 µg/mL at 1.6 h, respectively. Mean half-life in both samples were 16.4 and 25.2 h, respectively. The ratio of predicted AUC0-24 at steady state in TF (51.3 µg∙h/mL) to previously published minimum inhibitory concentration (MIC) of Aspergillus and Fusarium species was >100 and 25.7, respectively. CONCLUSIONS: This study demonstrated the detailed single-dose PK of voriconazole in TF after oral administration and simulated the predicted concentration curves in a multiple oral dosing. Based on the analyses of PK-PD, the simulation results indicated that repeated oral administration of voriconazole at 4.0 mg/kg/d achieves the ratio of AUC to MIC associated with treatment efficacy against Aspergillus species. The detailed PK-PD analyses against pathogenic fungi in TF can be used to provide evidence-based medicine for equine keratomycosis.

Evaluation of the Intracranial Flow Alteration during Manual Syringe and Continuous Pump Aspiration.

GOALS: While mechanical thrombectomy (MT) has been shown to be effective in the treatment of acute large vessel occlusions, adjunctive measures, such as balloon guide catheters (BGC) and aspiration techniques, are utilized heterogeneously. Clarifying the effects of aspiration applied to the anterior cerebral circulation with proximal flow arrest can shed light on embolic protection during MT. MATERIALS AND METHODS: Manual and pump aspiration were applied through a BGC in a synthetic cerebrovascular model with a 60 ml syringe and a Penumbra pump, respectively. Flow direction was observed during the procedure with fluorescent particles and ultraviolet light. Flow rates were monitored at the simulated internal carotid artery and middle cerebral artery (MCA). FINDINGS: Both aspiration methods produced retrograde flow in all the modeled cerebrovascular segments. In the syringe aspiration methods, an interval phase occurred during the experimental trial in which suction forces paused and MCA flow became anterograde through posterior communication artery collateral circulation. CONCLUSION: Flow patterns vary with different methods of aspiration. With proximal flow arrest, continuous aspiration methods induce constant retrograde flow in all vessels, whereas manual aspiration demonstrates various flow changes, including periods of anterograde flow during the procedure, which may be less effective at distal re-embolization prevention.

Lysophosphatidic acid signaling regulates the KLF9-PPARγ axis in human induced pluripotent stem cell-derived neurons.

Lysophosphatidic acid (LPA) is a lipid signaling molecule that plays several significant roles in the nervous system during development and injury. In this study, we differentiated human induced pluripotent stem cells (iPSCs) into neurons as an in vitro model to examine the specific effects of LPA. We demonstrated that LPA activates peroxisome proliferator-activated receptor gamma (PPARγ), a ligand-activated nuclear receptor, as well as its cognate receptor LPA1 on human iPSC-derived neurons to enhance proliferation and neurite outgrowth. Furthermore, we found that the gene expression of Kruppel-like factor 9 (KLF9), a member of the large KLF transcription factor family, was induced by LPA treatment. Knockdown of KLF9 decreased proliferation and neurite outgrowth in vehicle- and LPA-treated IPSC-derived neurons compared to cells expressing KLF9. In conclusion, LPA plays dual roles as a ligand mediator through the activation of cell surface G-coupled protein receptors and as an intracellular second messenger through the activation of PPARγ. We discuss the contribution of the LPA1-PPARγ-KLF9 axis to neurite outgrowth and proliferation in human iPSC-derived neurons.

Novel balloon-and-aspiration method for cerebral venous sinus thrombosis: dental-floss technique.

Cerebral venous sinus thrombosis is sometimes fatal. The standard treatment for sinus thrombosis is anticoagulation, but endovascular intervention must be considered when medical treatment fails. Mechanical thrombectomy is usually required when a large clot burden exits. Unfortunately, in sinus thrombosis attributable to a clot burden larger than that in an intracranial artery, the conventional technique used for intraarterial acute stroke intervention with a stent retriever and/or aspiration is not very effective. The authors describe here their endovascular approach to mechanical thrombectomy for sinus thrombosis using aspiration combined with angioplasty balloon support.

Utility of a Y-configured stentriever technique as a rescue method of thrombectomy for an intractable rooted thrombus located on the middle cerebral artery bifurcation: technical note.

Mechanical thrombectomy with stentriever and/or aspiration is the new gold standard for the treatment of acute strokes with large-vessel occlusion. As many as 20% of cases remain refractory to current stentriever and/or aspiration devices. "Saddle clots" obstructing a bifurcation may be a particular challenge for recanalization with conventional techniques and devices. The authors describe an alternative technique to bifurcation occlusions resistant to the conventional mechanical thrombectomy approach in which they simultaneously deployed 2 stentrievers into both branches of an occluded bifurcation. This stentriever Y-configuration was very effective in managing a challenging intracranial bifurcation occlusion.

Lysophospholipid-Related Diseases and PPARγ Signaling Pathway.

The nuclear receptor superfamily includes ligand-inducible transcription factors that play diverse roles in cell metabolism and are associated with pathologies such as cardiovascular diseases. Lysophosphatidic acid (LPA) belongs to a family of lipid mediators. LPA and its naturally occurring analogues interact with G protein-coupled receptors on the cell surface and an intracellular nuclear hormone receptor. In addition, several enzymes that utilize LPA as a substrate or generate it as a product are under its regulatory control. Recent studies have demonstrated that the endogenously produced peroxisome proliferator-activated receptor gamma (PPARγ) antagonist cyclic phosphatidic acid (cPA), which is structurally similar to LPA, inhibits cancer cell invasion and metastasis in vitro and in vivo. We recently observed that cPA negatively regulates PPARγ function by stabilizing the binding of the co-repressor protein, a silencing mediator of retinoic acid, and the thyroid hormone receptor. We also showed that cPA prevents neointima formation, adipocyte differentiation, lipid accumulation, and upregulation of PPARγ target gene transcription. The present review discusses the arbitrary aspects of the physiological and pathophysiological actions of lysophospholipids in vascular and nervous system biology.

Protective Effects of Tormentic Acid, a Major Component of Suspension Cultures of Eriobotrya japonica Cells, on Acetaminophen-Induced Hepatotoxicity in Mice.

An acetaminophen (APAP) overdose can cause hepatotoxicity and lead to fatal liver damage. The hepatoprotective effects of tormentic acid (TA) on acetaminophen (APAP)-induced liver damage were investigated in mice. TA was intraperitoneally (i.p.) administered for six days prior to APAP administration. Pretreatment with TA prevented the elevation of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (T-Bil), total cholesterol (TC), triacylglycerol (TG), and liver lipid peroxide levels in APAP-treated mice and markedly reduced APAP-induced histological alterations in liver tissues. Additionally, TA attenuated the APAP-induced production of nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and IL-6. Furthermore, the Western blot analysis showed that TA blocked the protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2), as well as the inhibition of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) activation in APAP-injured liver tissues. TA also retained the superoxidase dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) in the liver. These results suggest that the hepatoprotective effects of TA may be related to its anti-inflammatory effect by decreasing thiobarbituric acid reactive substances (TBARS), iNOS, COX-2, TNF-α, IL-1ß, and IL-6, and inhibiting NF-κB and MAPK activation. Antioxidative properties were also observed, as shown by heme oxygenase-1 (HO-1) induction in the liver, and decreases in lipid peroxides and ROS. Therefore, TA may be a potential therapeutic candidate for the prevention of APAP-induced liver injury by inhibiting oxidative stress and inflammation.

Short-term treatment with a 2-carba analog of cyclic phosphatidic acid induces lowering of plasma cholesterol levels in ApoE-deficient mice.

Plasma cholesterol levels are associated with an increased risk of developing atherosclerosis. An elevated low-density lipoprotein cholesterol (LDL-C) level is a hallmark of hypercholesterolemia in metabolic syndrome. Our previous study suggested that when acetylated LDL (AC-LDL) was co-applied with a PPARγ agonist, rosiglitazone (ROSI), many oil red O-positive macrophages could be observed. However, addition of cyclic phosphatidic acid (cPA) to ROSI-stimulated macrophages completely abolished oil red O-stained cells, indicating that cPA inhibits PPARγ-regulated AC-LDL uptake. This study aimed to determine whether metabolically stabilized cPA, in the form of a carba-derivative of cPA (2ccPA), could reduce plasma cholesterol levels and affect the expression of genes related to atherosclerosis in apolipoprotein E-knockout (apoE(-/-)) mice. 2ccPA reduced LDL-C levels in these mice (n = 3) from 460 to 330 mg/ml, from 420 to 350 mg/ml, and 420 to 281 mg/ml under a western-type diet. 2ccPA also reduced expression of lipid metabolism-related genes, cytokines, and chemokines in ApoE-deficient mice on a high-fat diet. Taken together, these results suggest that 2ccPA governs anti-atherogenic activities in the carotid arteries of apoE-deficient mice.

Cyclic phosphatidic acid induces G0/G1 arrest, inhibits AKT phosphorylation, and downregulates cyclin D1 expression in colorectal cancer cells.

Lysophosphatidic acid (LPA) and its analogs are well-known mitogens for various cell types. Many reports have confirmed that several types of cancer cell produce LPA to promote survival, growth and tumorigenesis. This indicates that the interface between the LPA signaling pathway and the cell cycle signaling system is critical to the control of cancer cell proliferation. However, our previous study indicated that cyclic phosphatidic acid (cPA), which is structurally similar to LPA, inhibits the proliferation and migration of colon cancer cells. It has been reported that cPA shows several biological activities not shown by LPA. However, understanding of the detailed molecular and cellular mechanism underlying the regulation of the cell cycle by cPA is still in its infancy. In this study, we investigated the effect of cPA treatment on human DLD-1 colon cancer cells by analyzing cell cycle dynamics, gene expression, and AKT phosphorylation. Our findings indicate that cPA inhibits cell cycle progression in DLD-1 colon cancer cells via the downregulation of cyclin D1 and the inhibition of AKT phosphorylation.

Cyclic phosphatidic acid inhibits alkyl-glycerophosphate-induced downregulation of histone deacetylase 2 expression and suppresses the inflammatory response in human coronary artery endothelial cells.

Activation of the endothelium by alkyl-glycerophosphate (AGP) has been implicated in the development of atherosclerosis. Our previous study suggested that cyclic phosphatidic acid (cPA) inhibits arterial wall remodeling in a rat model in vivo. However, the mechanisms through which specific target genes are regulated during this process remain unclear. Here, we examined whether cPA inhibited AGP-induced expression of class I histone deacetylases (HDACs, namely HDAC1, HDAC2, HDAC3, and HDAC8), which may affect subsequent transcriptional activity of target genes. Our experimental results showed that human coronary artery endothelial cells (HCAECs) expressed high levels of HDAC2 and low levels HDAC1, HDAC3, and HDAC8. Moreover, AGP treatment induced downregulation of HDAC2 expression in HCAECs. However, cotreatment with cPA inhibited this downregulation of HDAC2 expression. Interestingly, treatment with AGP increased the expression and secretion of endogenous interleukin (IL)-6 and IL-8; however, this effect was inhibited when HCAECs were cotreated with cPA or the synthetic peroxisome proliferator-activator receptor gamma (PPARγ) antagonist T0070907. Thus, our data suggested that cPA may have beneficial effects in inflammation-related cardiovascular disease by controlling HDAC2 regulation.

[Radiation Dose Reduction through the Optimization of Mask Images in Cerebral Angiography].

PURPOSE: To verify the effectiveness of optimizing the number of mask images in DSA for radiation dose reduction during cerebral angiography. METHODS: A total of 60 angiography sessions in 2 times for 30 patients performed by the same operator were included in this study. In order to compare the effects of optimization to change the injection delay time of DSA from 1 s to the shortest possible time, the number of mask images, the number of imaging frames, and radiation doses between sessions were compared and analyzed retrospectively. RESULTS: In one DSA run, the number of mask images was decreased from 6 (5-7) to 3 (2-3) frames (p<0.01)/57.1% (median [IQR]/reduction rate), the number of imaging frames was decreased from 34 (32-36) to 32 (29-34) frames (p<0.01)/7.9%, and the radiation dose was decreased from 33 (23-47) to 30 (21-40) mGy (p<0.01)/8.3%. In magnification angiography, the reductions rate was significantly increased. In one angiography session, the number of mask images was decreased from 45 (35-72) to 19 (16-34) frames (p<0.01)/54.6%, the number of imaging frames was decreased from 242 (199-385) to 211 (181-346) frames (p<0.01)/8.3%, the radiation dose of DSA was decreased from 295 (190-341) to 242 (167-305) mGy (p<0.01)/11.6%, and the total radiation dose was decreased from 369 (259-418) to 328 (248-394) mGy (p<0.01)/7.5%. CONCLUSION: Using the shortest possible injection delay time for the number of mask image optimization was an effective radiation dose reduction method.

Pork Liver Decomposition Product May Improve Frontal Lobe Function in Humans-Open Trial.

Porcine Liver Decomposition Product (PLDP) was obtained by treating pig liver homogenate with protease and filling it into capsules. We have already confirmed from three clinical trials that PLDP enhances visual memory and delays memory recall, and we believe that its activity is due to various phospholipids, including phosphatidylcholine (PC). In this study, we clinically evaluated PLDP for depressive symptoms caused by a decline in cognitive function. This clinical trial was conducted using the Revised Hasegawa Dementia Scale (HDS-R). The HDS-R (maximum score is 30 points) is a test similar to the Mini-Mental State Examination (MMSE), which is commonly used in Japan. Dementia is suspected if the score falls below 20 on the HDS-R. Additionally, in a previous clinical trial, there was no change in scores in the placebo group after three doses of the HDS-R. In order to clearly confirm the effectiveness of PLDP, this study was conducted under stricter conditions (HDS-R points of 15 to 23) than previous clinical trials (all participants had scores of 20 or higher). Therefore, from ethical considerations, a clinical trial was conducted using the scores before PLDP administration as a control. In this study, PLDP was administered orally at 4 capsules per day, and the HDS-R was confirmed 2 and 4 weeks after administration. A significant increase in HDS-R scores was observed at 2 and 4 weeks after PLDP administration. Additionally, regarding each item of the HDS-R, PLDP significantly increased 2 and 4 weeks after oral administration for the question items assessing delayed recall, and the question item assessing verbal fluency tasks was recognized. From the above results, we confirmed the reproducibility of the effect of PLDP in improving the delayed recall of verbal memories. Furthermore, increasing scores on verbal fluency tasks suggest that PLDP may enhance frontal lobe function and prevent or improve depressive symptoms. The effects observed in this study may differ from the mechanisms of action of existing antidepressants, and we believe that this may lead to the discovery of new antidepressants.

Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells.

Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA-PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 µM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance.

Highly purified, multi-wall carbon nanotubes induce light-chain 3B expression in human lung cells.

Bronchial epithelial cells are targets of inhalation and play a critical role in the maintenance of mucosal integrity as mechanical barriers against various particles. Our previous result suggest that vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. Increasing evidence suggests that autophagy may critically influence vital cellular processes such as apoptosis, cell proliferation and inflammation and thereby may play a critical role in pulmonary diseases. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles. In this study, the authors focus on the autophagic responses of HTT2800 exposure. The HTT2800-exposed cells induced LC3B expression and induced cell growth inhibition.

The clinical results of transcervical carotid artery stenting and frequency chosen as the approach route of carotid artery stenting in 1,067 consecutive cases.

BACKGROUND: Carotid artery stenting (CAS) is generally performed via a transfemoral approach. A transbrachial approach is usually chosen as an alternative when CAS via a transfemoral approach is difficult. At our institutions, a transcervical approach is chosen when the previous two approach routes are not available. We reviewed CAS cases treated via the transcervical route in our 1,067 CAS series to investigate the safety, feasibility, and frequency of this procedure as an approach route of CAS. METHODS: We performed 1,067 CAS procedures in 1,067 consecutive cases between December 2002 and June 2011. Initially, a transfemoral route was chosen, and secondarily a transbrachial route, the last choice was a transcervical route. A transbrachial approach was chosen in 96 (9.0%) cases and a transcervical approach in ten (0.9%). We reviewed the characteristics and outcomes of CAS performed via a transcervical approach. RESULTS: CAS was successfully performed on all ten transcervical-approach patients. Eight procedures were performed under local anesthesia and two under general anesthesia. Perioperative morbidity and mortality were both 0%. The modified Rankin scale (mRS) showed no deterioration at 3 months except for one case whose mRS became five because of an embolic stroke after aortic valve replacement. CONCLUSIONS: CAS via a transcervical approach was safe and feasible, and its frequency chosen as an approach route was 0.9%. This procedure can be an alternative to transfemoral or transbrachial approaches when CAS via either of these approaches is too difficult.