Variations in origin of the superior thyroid artery: an update for the head and neck surgeon.

Head and neck surgeons must have a thorough knowledge of head and neck vascular anatomy and its variations. This case report documents a variation in the superior thyroid artery encountered during a neck dissection and discusses the surrounding literature. A 55-year-old female with squamous cell carcinoma of the tongue underwent a partial glossectomy, right level I-IV neck dissection and reconstruction with a radial forearm free flap. During the procedure, an arterial branch was encountered arising 2-3cm caudal to the common carotid bifurcation. This variant branch was shown to represent the superior thyroid artery. On review of the literature, various classification systems of the superior thyroid artery origin have been described. Awareness of such anatomical variation is vital for the head and neck surgeon to avoid unexpected complication.

Use of a sternocleidomastoid muscle flap to protect the carotid artery during laryngectomy.

OBJECTIVES: This paper describes a simple method of securing tissue coverage of the great vessels at the initial surgery by rotating the divided sternal heads of the sternocleidomastoid muscle, a routine step during laryngectomy, and approximating them to the prevertebral fascia. The paper presents an illustrated case example where this technique in a salvage laryngectomy repair resulted in a protected vascular axis following a salivary leak. RESULTS: Since utilising this technique, there has been a marked reduction in the requirement of subsequent flap procedures to protect vessels, and no episodes of threatened or actual carotid blowout.

Nkx2-3 induces autophagy inhibiting proliferation and migration of vascular smooth muscle cells via AMPK/mTOR signaling pathway.

Vascular remodeling and restenosis are common complications after percutaneous coronary intervention. Excessive proliferation and migration of vascular smooth muscle cells (VSMCs) play important roles in intimal hyperplasia-induced vascular restenosis. NK2 Homeobox 3 (Nkx2-3), a critical member of Nkx family, is involved in tissue differentiation and organ development. However, the role of Nkx2-3 in VSMCs proliferation and migration remains unknown. In this study, we used carotid balloon injury model and platelet-derived growth factor-BB (PDGF)-treated VSMCs as in vivo and in vitro experimental models. EdU assay and CCK-8 assay were used to detect cell proliferation. Migration was measured by scratch test. Hematoxylin and eosin staining and immunohistochemistry staining were used to evaluate the intimal hyperplasia. The autophagy level was detected by fluorescent mRFP-GFP-LC3 in vitro and by transmission electron microscopy in vivo. It was shown that Nkx2-3 was upregulated both in balloon injured carotid arteries and PDGF-stimulated VSMCs. Adenovirus-mediated Nkx2-3 overexpression inhibited intimal hyperplasia after balloon injury, and suppressed VSMCs proliferation and migration induced by PDGF. Conversely, silencing of Nkx2-3 by small interfering RNA exaggerated proliferation and migration of VSMCs. Furthermore, we found that Nkx2-3 enhanced autophagy level, while the autophagy inhibitor 3-MA eliminated the inhibitory effect of Nkx2-3 on VSMCs proliferation and migration both in vivo and in vitro. Moreover, Nkx2-3 promoted autophagy in VSMCs by activating the AMP-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway. These results demonstrated for the first time that Nkx2-3 inhibited VSMCs proliferation and migration through AMPK/mTOR-mediated autophagy.

Anomalous innominate artery complicating tracheal surgical procedures.

OBJECTIVE: To highlight the importance of imaging in reducing an accidental injury to the anomalous brachiocephalic trunk and its branches during tracheal surgery. CASE REPORT: This paper reports two cases of accidental injury to the great vessels in the neck during tracheal surgery. The first incident occurred during a repeat tracheostomy, when the right common carotid artery was injured. On reviewing the computed tomography images, the bifurcation of the brachiocephalic artery was seen to the left of the midline, and the right common carotid artery was adherent just below the tracheostomy site. The second incident happened during surgery for tracheal stenosis, when there was an inadvertent injury to the main brachiocephalic trunk, which was adherent to the trachea in the lower neck region. CONCLUSION: For airway surgeons, radiological assessment of vascular structures in relation to the trachea prior to surgery is as important as the endoluminal airway assessment for the best outcome.

Adenosine kinase is critical for neointima formation after vascular injury by inducing aberrant DNA hypermethylation.

AIMS: Adenosine receptors and extracellular adenosine have been demonstrated to modulate vascular smooth muscle cell (VSMC) proliferation and neointima formation. Adenosine kinase (ADK) is a major enzyme regulating intracellular adenosine levels but is function in VSMC remains unclear. Here, we investigated the role of ADK in vascular injury-induced smooth muscle proliferation and delineated the mechanisms underlying its action. METHODS AND RESULTS: We found that ADK expression was higher in the neointima of injured vessels and in platelet-derived growth factor-treated VSMCs. Genetic and pharmacological inhibition of ADK was enough to attenuate arterial injury-induced neointima formation due to inhibition of VSMC proliferation. Mechanistically, using infinium methylation assays and bisulfite sequencing, we showed that ADK metabolized the intracellular adenosine and potentiated the transmethylation pathway, then induced the aberrant DNA hypermethylation. Pharmacological inhibition of aberrant DNA hypermethylation increased KLF4 expression and suppressed VSMC proliferation as well as the neointima formation. Importantly, in human femoral arteries, we observed increased ADK expression and DNA hypermethylation as well as decreased KLF4 expression in neointimal VSMCs of stenotic vessels suggesting that our findings in mice are relevant for human disease and may hold translational significance. CONCLUSION: Our study unravels a novel mechanism by which ADK promotes VSMC proliferation via inducing aberrant DNA hypermethylation, thereby down-regulating KLF4 expression and promoting neointima formation. These findings advance the possibility of targeting ADK as an epigenetic modulator to combat vascular injury.

Importance of ß2AR elevation for re-endothelialization capacity mediated by late endothelial progenitor cells in hypertensive patients.

Dysfunction of late endothelial progenitor cells (EPCs) has been suggested to be associated with hypertension. ß2-Adrenergic receptor (ß2AR) is a novel and key target for EPC homing. Here, we proposed that attenuated ß2AR signaling contributes to EPCs dysfunction, whereas enhanced ß2AR signaling restores EPCs' functions in hypertension. EPCs derived from hypertensive patients exhibited reduced cell number, impaired in vitro migratory and adhesion abilities, and impaired re-endothelialization after transplantation in nude mice with carotid artery injury. ß2AR expression of EPCs from hypertensive patients was markedly downregulated, whereas the phosphorylation of the p38 mitogen-activated protein kinase (p38-MAPK) was elevated. The cleaved caspase-3 levels were elevated in EPCs. The overexpression of ß2AR in EPCs from hypertensive patients inhibited p38-MAPK signaling, whereas it enhanced in vitro EPC proliferation, migration, and adhesion and in vivo re-endothelialization. The ß2AR-mediated effects were attenuated by treating the EPCs with a neutralizing monoclonal antibody against ß2AR, which could be partially antagonized by the p38-MAPK inhibitor SB203580. Moreover, shear stress stimulation, a classic nonpharmacological intervention, increased the phosphorylation levels of ß2AR and enhanced the in vitro and in vivo functions of EPCs from hypertensive patients. Collectively, the current investigation demonstrated that impaired ß2AR/p38-MAPK/caspase-3 signaling at least partially reduced the re-endothelialization capacity of EPCs from hypertensive patients. Restoration of ß2AR expression and shear stress treatment could improve their endothelial repair capacity by regulating the p38-MAPK/caspase-3 signaling pathway. The clinical significance of ß2AR in endothelium repair still requires further investigation.NEW & NOTEWORTHY Impaired ß2-adrenergic receptor (ß2AR) expression with an elevation of p38-MAPK/caspase-3 signaling at least partially contributes to the decline of re-endothelialization capacity of late endothelial progenitor cells (EPCs) from hypertensive patients. ß2AR gene transfer and shear stress treatment improve the late EPC-mediated enhancement of the re-endothelialization capacity in hypertensive patients through activating ß2AR/p38-MAPK/caspase-3 signaling. The present study is the first to reveal the potential molecular mechanism of the impaired endothelium-reparative capacity of late EPCs in hypertension after vascular injury and strongly suggests that ß2AR is a novel and crucial therapeutic target for increasing EPC-mediated re-endothelialization capacity in hypertension.

Surgical and embryological perspective of a big loop of internal carotid artery extending laterally beyond internal jugular vein.

Knowledge of variations of the internal carotid artery is significant to surgeons and radiologists. The internal carotid artery normally runs a straight course in the neck. Its anomalies can lead to its iatrogenic injuries. We report a case of a large loop of the internal carotid artery in a male cadaver aged about 75 years. The common carotid artery terminated by dividing it into the external carotid artery and internal carotid arteries at the level of the upper border of the thyroid cartilage. From the level of origin, the internal carotid artery coursed upwards, backwards and laterally, and formed a large loop behind the internal jugular vein. The variation was found on the left side of the neck and was unilateral. The uncommon looping of the internal carotid artery might result in altered blood flow to the brain and may lead to misperceptions in surgical, imaging, and invasive procedures.

4-Methoxyphenyl (E)-3-(Furan-3-yl) Acrylate Inhibits Vascular Smooth Muscle Cell Proliferation.

The Cordyceps extract exhibits antiproliferative potential in vascular smooth muscle cells (SMCs) through the mitogen-activated protein kinase signaling pathway. In this study, we aimed to identify the active compounds in the Cordyceps extract and analyze their role in remodeling the arterial wall. On investigation, we discovered the following active compound: 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate and synthesized it. We performed antiproliferation and antimigration assays in addition to an in vivo vessel wall remodeling experiment. Investigation of the mechanism adopted by the active compound to remodel the vessel was performed. The newly synthesized compound inhibited the proliferation and migration of SMCs. Treatment with the synthesized compound reduced neointima formation in the balloon-injured Sprague-Dawley rat model. In addition, this compound inhibited the activation of matrix metalloproteinase-2 and matrix metalloproteinase-9 in type I collagen-activated SMCs. Moreover, this compound suppressed the expression of cycloxygenase-2 (COX-2) in SMCs. Therefore, this compound can exert potential antiarteriosclerotic effects by modulating vessel wall remodeling. In conclusion, the newly synthesized 4-methoxyphenyl (E)-3-(furan-3-yl) acrylate might be an alternative therapeutic intervention for the treatment of atherosclerosis.

Carotid Stent Restenosis and Thrombosis in Rabbits: The Effect of Antiplatelet Agents.

BACKGROUND: The purpose of the study was the comparative assessment of ticagrelor and clopidogrel effects on carotid post-balloon injury (PBI) and on post carotid artery stenting (CAS) rate of in-stent restenosis (ISR) and in-stent thrombosis in atherosclerotic rabbits. METHODS: Forty-eight New Zealand white rabbits on high-fat diet were randomized into 4 groups: A1: PBI and clopidogrel (30 mg/kg/d), A2: PBI and ticagrelor (21 mg/kg twice daily), B1: PBI, CAS, and clopidogrel (30 mg/kg/d), B2: PBI, CAS, and ticagrelor (21 mg/kg twice daily). All rabbits received orally aspirin (10 mg/kg/d) and interventions were performed in their right carotid arteries (RCAs). Optical coherence tomography (OCT) and carotid angiography were performed at end point, while platelet aggregation and lipid profile were measured. After euthanasia both carotids were obtained for histological examination. RESULTS: In B1 group, 3 rabbits presented thrombotic total occlusion of the stents, while none such episode was observed in B2 group. The neointimal areas in RCAs, calculated by OCT, did not differ between A1 and A2 groups, and between B1 and B2 groups (P > .05). From the histological findings, the intima/(media + intima) percentage (%) in RCAs of balloon-injured rabbits did not present any difference between groups (P = .812). Similarly, the immunohistochemically determined accumulation of endothelial cells and macrophages on vascular walls was equivalent between groups (P > .05). CONCLUSION: Following carotid balloon injury and stenting, clopidogrel and ticagrelor did not show any differential effects on the extent of neointimal formation and ISR in atherosclerotic rabbits receiving aspirin. Three thrombotic stent occlusions were noted in the clopidogrel treatment group, but this finding was not statistically significant.

Ginsenoside Rg1 prevents vascular intimal hyperplasia involved by SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in a rat balloon injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Mey. is a traditional tonic that has been used for thousands of years, and has positive effects on vascular diseases. Ginsenoside Rg1 (GS-Rg1) is one of the active ingredients of Panax ginseng C. A. Mey. and has been shown to have beneficial effects against ischemia/reperfusion injury. Our previously study has found that GS-Rg1 can mobilize bone marrow stem cells and inhibit vascular smooth muscle proliferation and phenotype transformation. However, pharmacological effects and mechanism of GS-Rg1 in inhibiting intimal hyperplasia is still unknown. AIM OF THE STUDY: This study was aimed to investigate whether GS-Rg1 prevented vascular intimal hyperplasia, and the involvement of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1 axes. MATERIALS AND METHODS: Rats were operated with carotid artery balloon injury. The treatment groups were injected with 4, 8 and 16 mg/kg of GS-Rg1 for 14 days. The degree of intimal hyperplasia was evaluated by histopathological examination. The expression of α-SMA (α-smooth muscle actin) and CD133 were detected by double-label immunofluorescence. Serum levels of SDF-1α, SCF and soluble FKN (sFKN) were detected by enzyme linked immunosorbent assay (ELISA). The protein expressions of SCF, SDF-1α and FKN, as well as the receptors c-kit, CXC chemokine receptor type 4 (CXCR4) and CX3C chemokine receptor type 1 (CX3CR1) were detected by immunochemistry. RESULTS: GS-Rg1 reduced intimal hyperplasia by evidence of the values of NIA, the ratio of NIA/MA, and the ratio of NIA/IELA and the ratio of NIA/LA, especially in 16 mg/kg group. Furthermore, GS-Rg1 8 mg/kg group and 16 mg/kg group decreased the protein expressions of the SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes in neointima, meanwhile GS-Rg1 8 mg/kg group and 16 mg/kg group also attenuated the expressions of SDF-1α, SCF and sFKN in serum. In addition, the expression of α-SMA and CD133 marked smooth muscle progenitor cells (SMPCs) was decreased after GS-Rg1 treatment. CONCLUSIONS: GS-Rg1 has a positive effect on inhibiting vascular intimal hyperplasia, and the underlying mechanism is related to inhibitory expression of SDF-1α/CXCR4, SCF/c-kit and FKN/CX3CR1 axes.

Total Panax notoginseng saponin inhibits balloon injury-induced neointimal hyperplasia in rat carotid artery models by suppressing pERK/p38 MAPK pathways

Total Panax notoginseng saponin (TPNS) is the main bioactivity compound derived from the roots and rhizomes of Panax notoginseng (Burk.) F.H. Chen. The aim of this study was to investigate the effectiveness of TPNS in treating vascular neointimal hyperplasia in rats and its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups, sham (control), injury, and low, medium, and high dose TPNS (5, 10, and 20 mg/kg). An in vivo 2F Fogarty balloon-induced carotid artery injury model was established in rats. TPNS significantly and dose-dependently reduced balloon injury-induced neointimal area (NIA) (P<0.001, for all doses) and NIA/media area (MA) (P<0.030, for all doses) in the carotid artery of rats, and PCNA expression (P<0.001, all). The mRNA expression of smooth muscle (SM) α-actin was significantly increased in all TPNS groups (P<0.005, for all doses) and the protein expression was significantly increased in the medium (P=0.006) and high dose TPNS (P=0.002) groups compared to the injury group. All the TPNS doses significantly decreased the mRNA expression of c-fos (P<0.001). The medium and high dose TPNS groups significantly suppressed the upregulation of pERK1/2 protein in the NIA (P<0.025) and MA (P<0.004). TPNS dose-dependently inhibited balloon injury-induced activation of pERK/p38MAPK signaling in the carotid artery. TPNS could be a promising agent in inhibiting cell proliferation following vascular injuries.

Releasing incisions of the buccal periosteum adjacent to the lower molar teeth can injure the facial artery: an anatomical study.

PURPOSE: Periosteal releasing incision (PRI) techniques are often used with guided bone regeneration procedures. As complications such as intra- and postoperative bleeding have been noticed, we aimed to study and clarify these as related to the PRI, especially on the mandibular buccal periosteum. METHODS: Fourteen sides from seven fresh-frozen Caucasian cadaveric heads were used in this study. The seven cadavers were derived from two females and five males. The mean age at the time of death was 75.9 ± 10.8 years. The PRI was made using a no. 15c blade using a surgical microscope. Subsequently, the fat tissue lateral to the periosteum was slightly dissected. The diameter of the facial artery (or its branch) and closest relationship between the tooth and position of the artery was recorded. Finally, the artery was traced back proximally to clarify its origin. RESULTS: On all sides, the inferior labial artery (ILA) was identified in the fat tissue lateral to and close to the periosteum. The ILA was closest to the periosteum at the midpoint of the PRI (approximately between the first and second molar teeth area or 10 mm mesial to the apex of the retromolar pad). The mean diameter of the ILA was 2.72 ± 0.26 mm. CONCLUSION: This anatomical finding should encourage dentists to make the PRI incision without invading the tissue underneath the periosteum.

Total Panax notoginseng saponin inhibits balloon injury-induced neointimal hyperplasia in rat carotid artery models by suppressing pERK/p38 MAPK pathways.

Total Panax notoginseng saponin (TPNS) is the main bioactivity compound derived from the roots and rhizomes of Panax notoginseng (Burk.) F.H. Chen. The aim of this study was to investigate the effectiveness of TPNS in treating vascular neointimal hyperplasia in rats and its mechanisms. Male Sprague-Dawley rats were randomly divided into five groups, sham (control), injury, and low, medium, and high dose TPNS (5, 10, and 20 mg/kg). An in vivo 2F Fogarty balloon-induced carotid artery injury model was established in rats. TPNS significantly and dose-dependently reduced balloon injury-induced neointimal area (NIA) (P<0.001, for all doses) and NIA/media area (MA) (P<0.030, for all doses) in the carotid artery of rats, and PCNA expression (P<0.001, all). The mRNA expression of smooth muscle (SM) α-actin was significantly increased in all TPNS groups (P<0.005, for all doses) and the protein expression was significantly increased in the medium (P=0.006) and high dose TPNS (P=0.002) groups compared to the injury group. All the TPNS doses significantly decreased the mRNA expression of c-fos (P<0.001). The medium and high dose TPNS groups significantly suppressed the upregulation of pERK1/2 protein in the NIA (P<0.025) and MA (P<0.004). TPNS dose-dependently inhibited balloon injury-induced activation of pERK/p38MAPK signaling in the carotid artery. TPNS could be a promising agent in inhibiting cell proliferation following vascular injuries.

Adventitial fibroblast-derived vascular endothelial growth factor promotes vasa vasorum-associated neointima formation and macrophage recruitment.

AIMS: Adventitial vasa vasorum provides oxygen and nourishment to the vascular wall, but whether it regulates vascular disease remains unclear. We have previously shown that an increased expression of VEGF (vascular endothelial growth factor) is associated with macrophage infiltration. This study aims to determine whether adventitial fibroblast (AF)-derived VEGF increases the number of vasa vasorum contributing to neointima formation through macrophage recruitment. METHODS AND RESULTS: In rat balloon injury model, vasa vasorum count was increased particularly in the adventitia accompanied by cell proliferation and VEGF expression. Both endogenous and PKH26-labelled exogenous macrophages were mainly distributed in adventitia around vasa vasorum. Interestingly, perivascular delivery of Ranibizumab preferentially concentrated in adventitia resulted in a decrease of neointima formation with concurrent reduction of vasa vasorum count and macrophage infiltration. AFs with adenovirus-mediated VEGF over-expression delivered to the adventitia significantly enhanced these pathological changes after injury. In Tie2-cre/Rosa-LoxP-RFP mice, endothelial cells were increased in the adventitia after wire injury. By using multiphoton laser scanning microscopy, macrophage rolling, adhesion and transmigration were observed in vasa vasorum. Moreover, adoptive transfer of macrophages accelerated injury-induced neointima formation. VEGF-neutralizing antibody administration also attenuated wire injury-induced neointima formation and macrophage infiltration. In primary cultured AFs, exogenous VEGF increased VEGF expression and secretion in a time- and dose-dependent manner. AF-conditioned medium promoted endothelial cell angiogenesis, vascular cell adhesion molecule-1 expression and macrophage adhesion was blocked by VEGF-neutralizing antibody and VEGFR2 inhibitor ZM323881, which also inhibited activation of VEGFR2/ERK1/2 pathway. CONCLUSION: These results demonstrate that AF-derived VEGF plays a significant role in the increase of vasa vasorum count which is involved in macrophage recruitment and neointima formation.

Proximal penholding method - A variant to enhance safety of ultrasoundguided central venous cannulation: A prospective pilot study.

Aims: A significant incidence of Posterior Vessel Wall Puncture (PVWP) was reported during ultrasound guidance (USG) for internal jugular vein (IJV) catheterization. We studied a new technique of USGIJV cannulation to minimize or avoid PVWP, thereby decreasing overall complication rate, irrespective of the operators' experience level. Materials and Methods: After ethical approval, a prospective study was conducted on adult patients of either gender between 18-65 years of age, belonging to the American Society of Anesthesiologists Physical Status I-III, undergoing general anesthesia and requiring USG-guided IJV cannulation. After induction of general anesthesia and intubation, USG-guided IJV cannulation was done using technique of "proximal pen-holding method" in patients placed in supine position with neck rotated in 15° rotation to the opposite side. The primary outcome was defined as success rate of USG-guided IJV cannulation and incidence of PVWP. The secondary outcome was the incidences of complications such as arterial puncture, adjacent tissue damage, and performer's ease of the procedure (0-10 scale; 0 denoting no ease and extreme difficulty and 10 denoting extreme ease and no difficulty). Results: In 135 patients, right IJV puncture, guidewire, and central line insertion were achieved in single attempt without any PVWP by nine operators which included two anesthesia consultants and seven senior registrars. No complications were reported and ease of procedure were rated as median (interquartile range) of 10 (10). Conclusions: The "proximal pen-holding method" for real-time USG-IJV cannulation helped in avoiding PVWP with lesser complication rate and greater performer's ease.

Usefulness of a New Electronic Conductivity Device with a Pedicle Probe and a Multi-axis Angiography Unit for Inserting a C1 Lateral Mass Screw Safely and Tightly: A Technical Note.

The C1 lateral mass screw (LMS) is widely used as one of the screws for atlantoaxial fixation. Tight bicortical screwing from the posterior to anterior cortical margin of the atlas is recommended. However, important structures, such as the internal carotid artery, are located around this area so precision is required to avoid injuring them. We describe the usefulness of a new electronic conductivity device (ECD) with a pedicle probe and a multi-axis angiography unit for inserting the C1 LMS. Four consecutive patients who were treated with C1 and C2 posterior fixation using an ECD and a multi-axis angiography unit in the hybrid operating room were included. All patients were treated successfully. Seven of eight bicortical screws could be inserted into the perfectly ideal location. The median (interquartile range) distance from the anterior margin of the atlas to the tip of the screw was 0.81 mm (0.43, 1.21 mm). This study suggested that the ECD and multi-axis angiography unit are useful for inserting the C1 LMS safely and tightly.

Adenosine-induced transient hypotension for carotid artery injury during endoscopic skull-base surgery: case report and review of the literature.

BACKGROUND: As the management of ventral skull-base pathology has transitioned from open to endonasal treatment, there has been an increased focus on the prevention and endoscopic endonasal management of internal carotid artery (ICA) and major vascular injury. The use of adenosine to induce transient hypotension or flow arrest has been previously described during intracranial aneurysm surgery; however, there have been no reports of the technique being used during endonasal skull-base surgery to achieve hemostasis following major vascular injury. METHODS: Case report (n = 1) and literature review. RESULTS: A 25-year-old female underwent attempted endoscopic endonasal resection of an advanced right-sided chondrosarcoma. During resection of the tumor, brisk arterial bleeding was encountered consistent with focal injury to the right cavernous ICA. Stable vascular hemostasis could not be achieved with tamponade. An intravenous bolus dose of adenosine was administered to induce a transient decrease in systemic blood pressure and facilitate placement of the muscle patch over the direct site of vascular injury. The patient subsequently underwent endovascular deconstruction of the right ICA. CONCLUSION: This is the first reported use of adenosine to induce transient hypotension for a major vascular injury sustained during endonasal skull-base surgery. Based on well-established safety data from neurosurgical application, adenosine has the potential to be used as a safe and effective adjunctive technique in similar endonasal circumstances and may represent an additional tool in the armamentarium of the skull-base surgeon. Surgeons should consider having adenosine available when a risk of ICA injury is anticipated.

Linagliptin protects rat carotid artery from balloon injury and activates the NRF2 antioxidant pathway.

Percutaneous coronary intervention (PCI) is main treatment for acute coronary syndrome (ACS). However, restenosis caused by PCI-induced injury influences the outcome of patients. Linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has been reported to ameliorate intimal hyperplasia post vascular injury. The underlying mechanisms by which linagliptin protects against balloon injury are unclear and require to be explored. Herein, Wistar rats with carotid artery balloon injury were given 1, 2 or 3 mg/kg/day linagliprin for 6 weeks. We found that linagliptin attenuated vascular injury-mediated neointima formation in rats without affecting body weight and blood glucose levels. ELISA results indicated that linagliptin significantly reduced overproduction of cytokines including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and IL-6 post balloon injury. By detecting the level of malondialdehyde (MDA) and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), we found that linagliptin prevented balloon injury-induced oxidative stress. Additionally, linagliptin decreased the level of Kelch ECH-associating protein 1 (KEAP1) compared with injury group. Results of Western blots and electrophoretic mobility shift assay (EMSA) demonstrated that linagliptin augmented nuclear accumulation of nuclear factor-E2-related factor 2 (NRF2) and its binding ability to target genes in rats with balloon injury. Moreover, heme oxygenase-1 (HO-1) and NAD (P) H quinine oxidoreductase 1 (NQO1), two downstream targets of NRF2, were further up-regulated after linagliptin treatment compared with injury group. In conclusion, our data suggest that linagliptin protects carotid artery from balloon injury-induced neointima formation and activates the NRF2 antioxidant pathway.

Involvement of stromal cell-derived factor-1α (SDF-1α), stem cell factor (SCF), fractalkine (FKN) and VEGF in TSG protection against intimal hyperplasia in rat balloon injury.

BACKGROUND: Intimal hyperplasia is the major therapeutic concern after percutaneous coronary intervention. The aim of this study is to investigate effects of 2,3,4',5-tetrahydroxystilbene-2-O-ß-D glucoside (TSG) on intimal hyperplasia and the underling mechanisms through attenuating the expressions of stromal cell-derived factor-1α (SDF-1α)/CXCR4, stem cell factor (SCF)/c-kit and fractalkine (FKN)/CX3CR1, and through promoting re-endothelialization with vascular endothelial growth factor (VEGF). METHOD: Rats were operated with carotid artery balloon injury. The treatment groups were gavaged with 50 and 100 mg/kg/d of TSG. After 10 days of treatment, carotid artery pathological changes were evaluated by histology. Serum levels of SDF-1α, SCF, FKN and VEGF were detected by enzyme linked immunosorbent assay. The protein expressions of the receptors c-kit, CXCR4, CX3CR1, as well as CD34 and proliferating cell nuclear antigen (PCNA) were detected by immunochemistry. RESULTS: TSG dose-dependently inhibited balloon injury-induced intimal hyperplasia, as evidenced by reducing neointima area (NIA), neointima area/media area (NIA/MA), neointima area/internal elastic area (NIA/IELA), and by decreasing the protein expression of PCNA. TSG reduced serum levels of SDF-1α, SCF and FKN, and it also decreased the expressions of the corresponding receptors c-kit, CXCR4, CX3CR1 in neointima. Importantly, the level of VEGF in peripheral blood and the expression of CD34 in vascular walls were increased to promote re-endothelialization. CONCLUSIONS: This study clearly demonstrated that TSG was effective in inhibiting intimal hyperplasia, and this effect was mediated, at least in part, through the SCF/c-kit, SDF-1α/CXCR4 and FKN/CX3CR1 axes. Importantly, TSG could increase VEGF and CD34 to promote endothelial repair.

Ginsenoside Re inhibits vascular neointimal hyperplasia in balloon-injured carotid arteries through activating the eNOS/NO/cGMP pathway in rats.

Ginsenoside Re (GS-Re) is one of the main ingredients of ginseng, a widely known Chinese traditional medicine, and has a variety of beneficial effects, including vasorelaxation, antioxidative, anti-inflammatory, and anticancer properties. The aims of the present study were to observe the effect of GS-Re on balloon injury-induced neointimal hyperplasia in the arteries and to investigate the mechanisms underlying this effect. A rat vascular neointimal hyperplasia model was generated by rubbing the endothelium of the common carotid artery (CCA) with a balloon, and GS-Re (12.5, 25 or 50 mg/kg/d) were subsequently continuously administered to the rats by gavage for 14 days. After GS-Re treatment, the vessel lumen of injured vessels showed significant increases in the GS-Re 25.0 and 50.0 mg/kg/d (intermediate- and high-dose) groups according to H.E. staining. Additionally, a reduced percentage of proliferating cell nuclear antigen (PCNA)-positive cells and an increased number of SM α-actin-positive cells were detected, and the levels of NO, cyclic guanosine monophosphate (cGMP), and eNOS mRNA as well as the phos-eNOSser1177/eNOS protein ratio were obviously upregulated in the intermediate- and high-dose groups. Moreover, the promotive effects of GS-Re on NO and eNOS expression were blocked by L-NAME treatment to different degrees. These results suggested that GS-Re can suppress balloon injury-induced vascular neointimal hyperplasia by inhibiting VSMC proliferation, which is closely related to the activation of the eNOS/NO/cGMP pathway.