The effect of propofol on hypoxia- and TNF-α-mediated BDNF/TrkB pathway dysregulation in primary rat hippocampal neurons.

AIMS: Hypoxia and inflammation may lead to BDNF/TrkB dysregulation and neurological disorders. Propofol is an anesthetic with neuroprotective properties. We wondered whether and how propofol affected BDNF/TrkB pathway in hippocampal neurons and astrocytes. METHODS: Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF-α treatment. The expression of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms were investigated. RESULTS: Hypoxia and TNF-α reduced the expression of BDNF, which was reversed by pretreatment of 25 µM propofol in hippocampal neurons. Furthermore, hypoxia and TNF-α increased the phosphorylation of ERK and phosphorylation of CREB at Ser142, while reduced the phosphorylation of CREB at Ser133, which were all reversed by 25 µM propofol and 10 µM ERK inhibitor. In addition, hypoxia or TNF-α did not affect TrkB expression, truncation, or phosphorylation in hippocampal neurons and astrocytes. However, in hippocampal neurons, 50 µM propofol induced TrkB phosphorylation, which may be mediated by p35 expression and Cdk5 activation, as suggested by the data showing that blockade of p35 or Cdk5 expression mitigated propofol-induced TrkB phosphorylation. CONCLUSIONS: Propofol modulated BDNF/TrkB pathway in hippocampal neurons via ERK/CREB and p35/Cdk5 under the condition of hypoxia or TNF-α exposure.

Propofol via Antioxidant Property Attenuated Hypoxia-Mediated Mitochondrial Dynamic Imbalance and Malfunction in Primary Rat Hippocampal Neurons.

BACKGROUND: Hypoxia may induce mitochondrial abnormality, which is associated with a variety of clinical phenotypes in the central nervous system. Propofol is an anesthetic agent with neuroprotective property. We examined whether and how propofol protected hypoxia-induced mitochondrial abnormality in neurons. METHODS: Primary rat hippocampal neurons were exposed to propofol followed by hypoxia treatment. Neuron viability, mitochondrial morphology, mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) production were measured. Mechanisms including reactive oxygen species (ROS), extracellular regulated protein kinase (ERK), protein kinase A (PKA), HIF-1α, Drp1, Fis1, Mfn1, Mfn2, and Opa1 were investigated. RESULTS: Hypoxia increased intracellular ROS production and induced mPTP opening, while reducing ATP production, MMP values, and neuron viability. Hypoxia impaired mitochondrial dynamic balance by increasing mitochondrial fragmentation. Further, hypoxia induced the translocation of HIF-1α and increased the expression of Drp1, while having no effect on Fis1 expression. In addition, hypoxia induced the phosphorylation of ERK and Drp1ser616, while reducing the phosphorylation of PKA and Drp1ser637. Importantly, we demonstrated all these effects were attenuated by pretreatment of neurons with 50 µM propofol, antioxidant α-tocopherol, and ROS scavenger ebselen. Besides, hypoxia, propofol, α-tocopherol, or ebselen had no effect on the expression of Mfn1, Mfn2, and Opa1. CONCLUSIONS: In rat hippocampal neurons, hypoxia induced oxidative stress, caused mitochondrial dynamic imbalance and malfunction, and reduced neuron viability. Propofol protected mitochondrial abnormality and neuron viability via antioxidant property, and the molecular mechanisms involved HIF-1α-mediated Drp1 expression and ERK/PKA-mediated Drp1 phosphorylation.

Clinical evaluation of volume of interest imaging combined with metal artifact reduction reconstruction techniques in coiling and stent assisted coiling during neurointerventional procedures.

PURPOSE: Three-dimensional (3D) scans with flat detector angiographic systems are widely used for neurointerventions by providing detailed vascular information. However, its associated radiation dose and streak metal artifact generated by implanted treatment devices remain issues. This work evaluates the feasibility and clinical value of volume of interest imaging combined with metal artifact reduction (VOI+MAR) to generate high quality 3D images with reduced radiation dose and metal artifacts. MATERIAL AND METHODS: Full volume (FV) and VOI scans were acquired in 25 patients with intracranial aneurysms and treated with either endovascular coiling (n=9) or stent assisted coiling (n=16) procedures. FV and VOI scans were reconstructed with conventional syngo DynaCT and VOI +MAR prototype software, respectively. RESULTS: Quantitative evaluation results demonstrated that compared with standard FV syngo DynaCT images, overall image quality was improved in the VOI+MAR reconstructed images, with streak metal artifacts considerably reduced or even removed; details of soft tissue in the vicinity of the metal devices was well preserved or recovered in the majority of cases. Radiation dose to patients calculated by dose area product was found to be significantly reduced using VOI scans. CONCLUSION: This study confirmed the feasibility of using VOI+MAR prototype software to achieve high image quality of a small volume of clinical interest and to reduce radiation dose. This technique has potential to improve patient safety and treatment outcomes.

Increasing the selectivity to ethylene in the MTO reaction by enhancing diffusion limitation in the shell layer of SAPO-34 catalyst.

The zinc cation accommodation in the cavities of the shell layer and the facilitated aromatic formation over the zinc cation modified SAPO-34 with a core-shell like structure introduce extra diffusion limitation for bulky hydrocarbons, which increases the selectivity to ethylene and the ethylene to propylene ratio at the initial stage of the MTO reaction.

Three-dimensional image fusion of CTA and angiography for real-time guidance during neurointerventional procedures.

AIM: To evaluate the accuracy of three-dimensional (3D) images from two modalities-CT angiography (CTA) and digital subtraction angiography (DSA). Additionally, to explore the value of using preprocedural CTA for real-time guidance during neurointerventional procedures. MATERIALS AND METHODS: 25 patients with CTA-confirmed cerebral arterial lesions were enrolled. For 12 of these patients, 3D DSA images of the contrast medium-enhanced target vessel were acquired during the intervention and registered with the preprocedurally acquired CTA images for evaluation of the accuracy of image fusion, focusing on the target vessel and the lesion. For the other 13 patients, a low-dose non-contrast 3D angiographic scan was performed. The preprocedurally acquired CTA image was then registered with the coordinate of angiography and overlaid onto the live fluoroscopic image to provide interventional guidance. RESULTS: Based on visual inspection by two experienced physicians and quantitative evaluation, excellent accuracy in the 3D registration of the CTA and DSA was achieved for all 12 patients examined. Additionally, CTA could be used successfully to guide the interventional procedures, including both diagnostic DSA and stent treatment. The radiation dose and contrast medium use were compared with those used by conventional interventional procedures and both were found to be significantly reduced. CONCLUSIONS: 3D CTA and angiographic image fusion was approved as highly accurate for neurovasculature. Additionally, using the fusion technique to guide interventional procedures enhanced the workflow, and required much less radiation exposure and contrast medium use, thus helping to reduce potential risks and increase treatment safety.

CBCT-based 3D MRA and angiographic image fusion and MRA image navigation for neuro interventions.

Digital subtracted angiography (DSA) remains the gold standard for diagnosis of cerebral vascular diseases and provides intraprocedural guidance. This practice involves extensive usage of x-ray and iodinated contrast medium, which can induce side effects. In this study, we examined the accuracy of 3-dimensional (3D) registration of magnetic resonance angiography (MRA) and DSA imaging for cerebral vessels, and tested the feasibility of using preprocedural MRA for real-time guidance during endovascular procedures.Twenty-three patients with suspected intracranial arterial lesions were enrolled. The contrast medium-enhanced 3D DSA of target vessels were acquired in 19 patients during endovascular procedures, and the images were registered with preprocedural MRA for fusion accuracy evaluation. Low-dose noncontrasted 3D angiography of the skull was performed in the other 4 patients, and registered with the MRA. The MRA was overlaid afterwards with 2D live fluoroscopy to guide endovascular procedures.The 3D registration of the MRA and angiography demonstrated a high accuracy for vessel lesion visualization in all 19 patients examined. Moreover, MRA of the intracranial vessels, registered to the noncontrasted 3D angiography in the 4 patients, provided real-time 3D roadmap to successfully guide the endovascular procedures. Radiation dose to patients and contrast medium usage were shown to be significantly reduced.Three-dimensional MRA and angiography fusion can accurately generate cerebral vasculature images to guide endovascular procedures. The use of the fusion technology could enhance clinical workflow while minimizing contrast medium usage and radiation dose, and hence lowering procedure risks and increasing treatment safety.

Hepatic blood volume imaging with the use of flat-detector CT perfusion in the angiography suite: comparison with results of conventional multislice CT perfusion.

PURPOSE: To prospectively determine the feasibility of flat-detector (FD) computed tomography (CT) perfusion to measure hepatic blood volume (BV) in the angiography suite in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty patients with HCC were investigated with conventional multislice and FD CT perfusion. CT perfusion was carried out on a multislice CT scanner, and FD CT perfusion was performed on a C-arm angiographic system, before transarterial chemoembolization procedures. BV values of conventional and FD CT perfusion were measured within tumors and liver parenchyma. The arterial perfusion portion of CT perfusion BV was extracted from CT perfusion BV by multiplying it by a hepatic perfusion index. Relative values (RVs) for CT perfusion arterial BV and FD CT perfusion BV (FD BV) were defined by dividing BV of tumor by BV of parenchyma. Relationships between BV and RV values of these two techniques were analyzed. RESULTS: In all patients, both perfusion procedures were technically successful, and all 33 HCCs larger than 10 mm were identified with both imaging methods. There were strong correlations between the absolute values of FD BV and CT perfusion arterial BV (tumor, r = 0.903; parenchyma, r = 0.920; both P < .001). Bland-Altman analysis showed a mean difference of -0.15 ± 0.24 between RVs for CT perfusion arterial BV and FD BV. CONCLUSIONS: The feasibility of FD CT perfusion to assess BV values of liver tumor and surrounding parenchyma in the angiographic suite was demonstrated.

Computer-aided evaluation of the anatomical accuracy of hybrid SPECT/spiral-CT imaging of lesions localized in the neck and upper abdomen.

OBJECTIVE: The purpose of this study was to investigate the anatomical accuracy of hardware-based single-photon emission computed tomography/computed tomography (SPECT/CT) registration in the upper abdomen and neck. METHODS: The database consisted of 90 patients referred for SPECT/CT for diagnostic workup of either thyroid/parathyroid disease (n=46) or abdominal neuroendocrine tumours (n=44). In the first group, 99mTc-MIBI was used as the tracer and in the second 123I-metaiodobenzylguanidine (n=13), 111In-octreotide (n=28) or 99mTc-octreotide (n=3). For predefined structures represented by both modalities, the distances between the centres of gravity of their CT and SPECT representation were determined in a semiautomated manner. In cervical data sets, this analysis was performed for the submandibular salivary glands (n=92) and in abdominal data sets for 69 neoplastic foci. RESULTS: The mean distances were 5.7 ± 2.0 mm (range: 1.84-9.67 mm) in the neck and 6.8 ± 3.3 mm (range: 1.4-19.7 mm) in the abdomen. In 42 out of 92 of the cervical and 40 out of 69 of the abdominal data sets at least one of the X-direction-determined, Y-direction-determined, and Z-direction-determined distances was greater than the SPECT pixel width of 4.6 mm. CONCLUSION: The anatomical accuracy of hardware-based SPECT/CT fusion depends also on the region of the body studied. For example, in the neck and upper abdomen the accuracy is lower than in the lower lumbar spine. In clinical routine, SPECT/CT data sets acquired for the neck and upper abdomen should be regularly checked and corrected for SPECT/CT misalignment. This is, in particular, important when CT-based corrections of SPECT involving pixelwise data integration such as for attenuation correction are made.