Cognitive protection of sinomenine in type 2 diabetes mellitus through regulating the EGF/Nrf2/HO-1 signaling, the microbiota-gut-brain axis, and hippocampal neuron ferroptosis.

Recent years have witnessed a growing research interest in traditional Chinese medicine as a neuroprotective nutrient in the management of diabetic cognitive dysfunction. However, the underlying molecular mechanisms of sinomenine in mediating ferroptosis of hippocampal neurons have been poorly understood. This study sought to decipher the potential effect and molecular mechanism of sinomenine in the cognitive dysfunction following type 2 diabetes mellitus (T2DM). Multi-omics analysis was conducted to identify the microbiota-gut-brain axis in T2DM patient samples obtained from the publicly available database. In HT-22 cells, erastin was utilized to create a ferroptosis model, and streptozotocin was injected intraperitoneally to create a rat model of DM. It was noted that intestinal flora imbalance occurred in patients with T2DM-associated cognitive dysfunction. Sinomenine could reduce Erastin-induced hippocampus neuronal ferroptosis by increasing EGF expression. EGF protected hippocampal neurons against ferroptosis by activating the Nrf2/HO-1 signaling pathway. Furthermore, in vivo results confirmed that sinomenine blocked ferroptosis of hippocampal neurons and alleviated cognitive dysfunction in T2DM rats. Collectively, these results suggest that sinomenine confers neuroprotective effects by curtailing hippocampal neuron ferroptosis via the EGF/Nrf2/HO-1 signaling and microbiota-gut-brain axis. It may be a candidate for the treatment of diabetic cognitive dysfunction.

Dunaliella salina Alga Protects against Myocardial Ischemia/Reperfusion Injury by Attenuating TLR4 Signaling.

Myocardial ischemia/reperfusion (I/R) injury is marked by rapid increase in inflammation and not only results in myocardial apoptosis but also compromises the myocardial function. Dunaliella salina (D. salina), a halophilic unicellular microalga, has been used as a provitamin A carotenoid supplement and color additive. Several studies have reported that D. salina extract could attenuate lipopolysaccharides-induced inflammatory effects and regulate the virus-induced inflammatory response in macrophages. However, the effects of D. salina on myocardial I/R injury remain unknown. Therefore, we aimed to investigate the cardioprotection of D. salina extract in rats subjected to myocardial I/R injury that was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion. Compared with the vehicle group, the myocardial infarct size significantly decreased in rats that were pre-treated with D. salina. D. salina significantly attenuated the expressions of TLR4, COX-2 and the activity of STAT1, JAK2, IκB, NF-κB. Furthermore, D. salina significantly inhibited the activation of caspase-3 and the levels of Beclin-1, p62, LC3-I/II. This study is the first to report that the cardioprotective effects of D. salina may mediate anti-inflammatory and anti-apoptotic activities and decrease autophagy through the TLR4-mediated signaling pathway to antagonize myocardial I/R injury.

Runx1 regulates zebrafish neutrophil maturation via synergistic interaction with c-Myb.

Neutrophils play an essential role in the innate immune defense system in vertebrates. During hematopoiesis, the full function of neutrophils involves maturation of granules and related enzymes. Yet, transcription regulators that promote neutrophil maturation remain largely undefined. Here, two hematopoiesis-defective zebrafish mutants, runx1w84x and c-mybhkz3, were used to investigate the in vivo roles of Runx1 in cooperation with c-Myb in regulating neutrophil maturation. Loss of runx1 impairs primitive neutrophil development. Additional regulation of c-myb+/- and c-myb-/- induces a more severe phenotypes suggesting a synergistic genetic interaction between c-myb and runx1 in neutrophil maturation. Further studies revealed that the two transcription factors act cooperatively to control neutrophil maturation processes via transactivating a series of neutrophil maturation-related genes. These data reveal the in vivo roles of Runx1 in regulating primitive neutrophil maturation while also indicating a novel genetic and molecular orchestration of Runx1 and c-Myb in myeloid cell development. The study will provide new evidence on the regulation of neutrophil maturation during hematopoiesis.

Calycosin attenuates Angiostrongylus cantonensis-induced parasitic meningitis through modulation of HO-1 and NF-κB activation.

Angiostrongylus cantonensis causes a form of parasitic meningitis in humans. Albendazole (ABZ) kills nematode larvae in the brain. However, dead larvae can trigger a severe inflammatory response, resulting in brain damage. Accumulating evidence suggests that calycosin represents a potential anti-inflammatory therapeutic candidate. In this study, we investigated the combined effects of ABZ and calycosin in angiostrongyliasis caused by A. cantonensis in BALB/c mice. Inflammatory mediators (such as phospho-nuclear factor-κB, cyclooxygenase-2, matrix metalloproteinase-9, tumour necrosis factor-α and interleukin-1ß) are associated with the development of meningitis and immune inflammatory reactions. We found that A. cantonensis significantly induces inflammatory mediator production and increases the blood­brain barrier (BBB) permeability. However, co-administration of both ABZ and calycosin markedly suppressed meningitis and inflammatory mediator production and decreased the BBB permeability compared to treatment with a single drug. Furthermore, calycosin and ABZ plus calycosin treatment facilitated production of the antioxidant haem oxygenase-1 (HO-1). Moreover, co-therapy with ABZ and calycosin failed to mitigate angiostrongyliasis in the presence of tin-protoporphyrin IX, an HO-1-specific inhibitor. This finding suggests that the beneficial effects of ABZ plus calycosin treatment on the regulation of inflammation are mediated by the modulation of HO-1 activation. The present results provide new insights into the treatment of human angiostrongyliasis using co-therapy with ABZ and calycosin.

Impact of nasopharyngeal irradiation and gadolinium administration on changes in T1 signal intensity of the dentate nucleus in nasopharyngeal malignancy patients without intracranial abnormalities.

BACKGROUND: Irradiation has been found to increase T1 signal intensity (SI) of the dentate nucleus (DN) by accelerating the gadolinium deposition in patients after multiple gadolinium-based contrast agent (GBCA) administrations. Several reports have focused on this phenomenon in patients with brain tumors; however, data in patients receiving irradiation with no intracranial abnormalities (NIAs) are lacking. PURPOSE: To explore how nasopharyngeal irradiation affected SI changes on unenhanced T1 -weighted imaging (T1 WI) in the DN in nasopharyngeal malignancy (NPM) patients who presented with NIAs and who had multiple injection doses (IDs) of linear GBCAs. STUDY TYPE: Single-center, retrospective, case-control study. POPULATION: In all, 132 subjects: 66 NPM patients, 66 matched controls. FIELD STRENGTH/SEQUENCE: 1.5T and 3T/T1 WI, T2 WI, and fluid-attenuated inversion recovery (FLAIR). ASSESSMENT: Radiation doses (RDs) were calculated by a radiotherapy technician. SIs were measured by a radiologist. The DN-to-cerebellar white matter (CWM) SI ratios and their relative percentage change (Rchange ) were compared. STATISTICAL TESTS: Shapiro-Wilk test, paired t-test, independent t-test, Mann-Whitney U-test, Pearson and Spearman correlation. RESULTS: DN/CWM b ratios or R change from the NPM group were significantly higher than those from the control group (P < 0.001). No significant difference of DN/CWM a ratios was found between the two groups (P > 0.05). Positive correlations between R change , DN/CWM b ratio, and the number of IDs were found in both the NPM and control groups (P < 0.01). The overall changes of DN/CWM b ratio or R change between NPM and control groups were higher for the higher-IDs subgroup (≥10) than for the lower-IDs subgroup (<10). DATA CONCLUSION: Nasopharyngeal irradiation appeared to increase SI in T1 WI in NPM patients with NIAs and repeated GBCA administrations relative to control patients who also underwent GBCA administrations, especially when IDs ≥10. However, no significant association between R change and RDs to the DNs was found. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:250-259.

Angiostrongylus cantonensis infection induces MMP-9 and causes tight junction protein disruption associated with Purkinje cell degeneration.

Angiostrongylus cantonensis causes a human central nervous system (CNS) infection characterized by eosinophilic meningitis or meningoencephalitis. Individuals infected with A. cantonensis exhibit unbalanced walking. The mechanism of extensive neurological impairments of hosts caused by A. cantonensis larvae remains unclear. Tight junction proteins (e.g., claudin-5 and zonula occludens-1) are the most important regulators of paracellular permeability and cellular adhesion. In a previous study, we found that increased matrix metalloproteinase-9 (MMP-9) activity may be associated with blood-CNS barrier disruption and/or the degeneration of Purkinje cells in eosinophilic meningitis caused by A. cantonensis. In the present study, the co-localization of MMP-9 and tight junction proteins on the degeneration of Purkinje cells was measured via confocal laser scanning immunofluorescence microscopy. The statistical evidence indicated that MMP-9 correlated between tight junction protein disruption and Purkinje cell degeneration at 20 days post-infection with A. cantonensis. In conclusion, Purkinje cell degeneration is highly correlated with tight junction protein disruption via the MMP-9 activation pathway.

Exogenous GDF11 attenuates non-canonical TGF-ß signaling to protect the heart from acute myocardial ischemia-reperfusion injury.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor beta 1 (TGF-ß1) superfamily that reverses age-related cardiac hypertrophy, improves muscle regeneration and angiogenesis, and maintains progenitor cells in injured tissue. Recently, targeted myocardial delivery of the GDF11 gene in aged mice was found to reduce heart failure and enhance the proliferation of cardiac progenitor cells after myocardial ischemia-reperfusion (I-R). No investigations have as yet explored the cardioprotective effect of exogenous recombinant GDF11 in acute I-R injury, despite the convenience of its clinical application. We sought to determine whether exogenous recombinant GDF11 protects against acute myocardial I-R injury and investigate the underlying mechanism in Sprague-Dawley rats. We found that GDF11 reduced arrhythmia severity and successfully attenuated myocardial infarction; GDF11 also increased cardiac function after I-R, enhanced HO-1 expression and decreased oxidative damage. GDF11 activated the canonical TGF-ß signaling pathway and inactivated the non-canonical pathways, ERK and JNK signaling pathways. Moreover, administration of GDF11 prior to reperfusion protected the heart from reperfusion damage. Notably, pretreatment with the activin-binding protein, follistatin (FST), inhibited the cardioprotective effects of GDF11 by blocking its activation of Smad2/3 signaling and its inactivation of detrimental TGF-ß signaling. Our data suggest that exogenous GDF11 has cardioprotective effects and may have morphologic and functional recovery in the early stage of myocardial I-R injury. GDF11 may be an innovative therapeutic approach for reducing myocardial I-R injury.

Diffusion tensor imaging of microstructural alterations in the trigeminal nerve due to neurovascular contact/compression.

BACKGROUND: Several recent studies have focused on microstructural changes in the trigeminal nerve in trigeminal neuralgia using diffusion tensor imaging (DTI). However, alterations after microvascular decompression (MVD) have rarely been investigated. Furthermore, the trigeminal nerve of asymptomatic individuals also presenting with neurovascular contact/compression (NVC) has not yet been studied. METHODS: Thirty-four patients suffering from trigeminal neuralgia and 34 healthy age-matched controls, who were identified as having unilateral NVC signs, underwent both DTI and high-resolution magnetic resonance imaging (MRI) for comparison. All trigeminal neuralgia patients underwent a post-surgical MRI scan after 7 days and a follow-up MRI scan within 6-8 months after surgery. The apparent diffusion coefficients (ADCs) and fractional anisotropy (FA) values were measured from coronal images in which the nerves from the root exit point to the distal segment were clearly shown. RESULTS: In 34 trigeminal neuralgia patients, the absolute FA value was significantly lower on the affected side (mean FA, 0.34 ± 0.03) than on the unaffected side (mean FA, 0.37 ± 0.05, p < 0.001). The FA ratio was also significantly different between the trigeminal neuralgia group (RsFA, 0.92 ± 0.06) and the control group (RsFA, 0.99 ± 0.09) (p = 0.001). The absolute ADC value between the two sides in patients and the ratios of ADC between the trigeminal neuralgia and control groups did not show any significant differences (p = 0.21 and 0.29, respectively). However, in 34 healthy subjects presenting with signs of NVC, neither the FA value nor the ADC showed a difference between sides (p > 0.05). The FA ratio of patients showed a significant increase on two follow-up MRI scans compared to the preoperative FA (p = 0.02 and 0.002, respectively), while the ADC ratio showed a significant decrease at 6 months after MVD (p = 0.004). CONCLUSION: This study of trigeminal neuralgia due to NVC found that DTI indexes could reflect alterations in the affected trigeminal nerve. Furthermore, a reversible change after MVD surgery could be potentially valuable for monitoring the change in white matter of the trigeminal nerve.

Matrix metalloproteinase-2 and matrix metalloproteinase-9 in mice with ocular toxocariasis.

In ocular toxocariasis, Toxocara canis-induced inflammatory reaction can lead to eye destruction and granuloma, which is formed by immune cell infiltration and concurrent extensive remodeling tissue. Herein, the histomorphology of granuloma and proteinase production in the eye of T. canis-infected BALB/c mice were investigated. Pathological effects substantially increased after the infection culminated in a severe leukocyte infiltration and granuloma formation from days 4 to 56 post-inoculation. The matrix metalloproteinase (MMP)-2 and MMP-9 activities remarkably increased, compared with those of uninfected control, by gelatin zymography and Western blot analysis in ocular toxocariasis. Granuloma formation had a remarkably positive correlation with MMP-2 and MMP-9 levels. We suggested that T. canis larvae and leukocytes infiltrated from blood vessel both migrated into corpus adiposum orbitae. Activated leukocytes secreted MMP-2 and MMP-9, leading to fibronectin degradation. The imbalance of MMP-2/TIMP-2 and MMP-9/TIMP-1 may play a role in inflammatory cell infiltration and extracellular matrix degradation, forming granuloma, in ophthalmological pathogenesis of T. canis infection.

Naringenin inhibited migration and invasion of glioblastoma cells through multiple mechanisms.

Glioblastoma (GBM) is the most mortality brain cancer in the world. Due to high invasion and drug resistance cause the poor prognosis of GBM. Naringenin, an ingredient of citrus, exhibits many cellular functions such as antioxidant, anti-inflammation, and anticancer. Naringenin inhibits the migration of bladder and lung cancer via modulation of MMP-2 and/or MMP-9 activities, Naringenin inhibits migration and trigger apoptosis in gastric cancer cells through downregulation of AKT pathway. However, the effects of naringenin in GBM still remain to be elucidated. In this study, we reveal the molecular mechanisms of naringenin in the inhibition of migration and invasion in GBM. No overt alternation of cell proliferation was found in of GBM 8901 cells treated with different concentration of naringenin. Slight decreased cell viability was found in GBM 8401 cell treated with 200 and 300 µM naringenin. Significant reduction of migration and invasion as assayed by Boyden chamber analysis was found in of GBM cells treated with 100, 200, and 300 µM naringenin. Zymography analysis also revealed that the activities of MMP-2 and MMP-9 of GBM cells were significantly inhibited in response to 100, 200, or 300 µM naringenin treatment. Proteins of MMP-2 and MMP-9 were downregulated in naringenin treated GBM cells. In addition, naringenin also attenuated the activities of ERK and p38. Naringenin decreased mesenchymal markers (snail and slug) expression as revealed by Western blot analysis. Taken together, our findings indicated that naringenin eliminated the migration and invasion of GBM cells through multiple mechanisms including inhibition of MMPs, ERK, and p38 activities and modulation of EMT markers. Our results also suggested that naringenin may be a potential agent to prevent metastasis of GBM.

Lumbrokinase attenuates myocardial ischemia-reperfusion injury by inhibiting TLR4 signaling.

Lumbrokinase, a novel antithrombotic agent, purified from the earthworm Lumbricus rubellus, has been clinically used to treat stroke and cardiovascular diseases. However, inflammatory responses associated with the cardioprotective effect of lumbrokinase remain unknown. In this study, the signaling pathways involved in lumbrokinase-inhibited expressions of inflammation mediators were investigated in rats subjected to myocardial ischemia-reperfusion (I-R) injury. The left main coronary artery of anesthetized rats was subjected to 1h occlusion and 3h reperfusion. The animals were treated with/without lumbrokinase and the severities of I-R-induced arrhythmias and infarction were compared. Lumbrokinase inhibited I-R-induced arrhythmias and reduced mortality, as well as decreased the lactate dehydrogenase levels in carotid blood. Lumbrokinase also inhibited the enhancement of I-R induced expressions of cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), and matrix metalloproteinase (MMP)-9 through toll-like receptor 4 (TLR4) signaling pathway. Moreover, our results demonstrated that stimulation with lumbrokinase decreases the phosphorylation of JNK, IκB, and NF-κB. These findings suggested that lumbrokinase is a potent cardioprotective drug in rats with I-R injury. The cardioprotective effects of lumbrokinase may be correlated with its inhibitory effect on the I-R-induced expressions of COX-2, iNOS and MMP-9, mediated by TLR4 signaling through JNK and NF-κB pathways.

Molecular evaluation of thrombosis using X-ray phase contrast imaging with microbubbles targeted to P-selectin in mice.

OBJECTIVES: X-ray phase contrast imaging (PCI) provides excellent image contrast by utilizing the phase shift. The introduction of microbubbles into tissues can cause a phase shift to make microbubbles visibly identified on PCI. In this study, we assessed the feasibility of targeted microbubble-based PCI for the detection of thrombosis. METHODS: The absorption and phase contrast images of P-selectin-targeted microbubbles (MBP) were obtained and compared in vitro. MBP, control IgG-targeted microbubbles (MBC), and unbound microbubbles (MBU) were tested for binding specificity on thrombi expressing P-selectin. MBP were used as molecular PCI probes to evaluate P-selectin expression in a mouse model of arteriovenous shunt thrombosis that was created using PE tubes in the bypass outside of the mouse body. RESULTS: PCI clearly showed the microbubbles not viewable via absorption contrast imaging (ACI). In vitro attachment of MBP (91.60 ± 11.63) to thrombi was significantly higher than attachment of MBC (17.80 ± 4.02, P < 0.001) or MBU (9.80 ± 2.59, P < 0.001). In the mouse model of arteriovenous shunt thrombosis, the binding affinity of MBP (15.50 ± 6.25) was significantly greater than that of MBC (0.50 ± 0.84, P < 0.001) or MBU (0.33 ± 0.52, P < 0.001). CONCLUSIONS: Our results indicate that molecular PCI may be considered as a novel and promising imaging modality for the investigation of thrombosis. KEY POINTS: • Small thrombi are rarely detected by conventional radiography. • Phase contrast imaging (PCI) provides higher contrast and spatial resolution than conventional radiography. • P-selectin targeted microbubbles detected by PCI may suggest early thrombosis.

Association of Brachial-Ankle Pulse Wave Velocity with Asymptomatic Intracranial Arterial Stenosis in Hypertension Patients.

BACKGROUND: Intracranial arterial stenosis is a common cause of ischemic stroke in Asians. We therefore sought to explore the relationship of brachial-ankle pulse wave velocity and intracranial arterial stenosis in 834 stroke-free hypertensive patients. METHODS: Intracranial arterial stenosis was evaluated through computerized tomographic angiography. Brachial-ankle pulse wave velocity was measured by an automated cuff device. RESULTS: The top decile of brachial-ankle pulse wave velocity was significantly associated with intracranial arterial stenosis (P = .027, odds ratio = 1.82; 95% confidence interval: 1.07-3.10). The patients with the top decile of brachial-ankle pulse wave velocity showed 56% higher risk for the presence of intracranial arterial stenosis to the whole population, which was more significant in patients younger than 65 years old. We also found that brachial-ankle pulse wave velocity related to both intracranial arterial stenosis and homocysteine. CONCLUSION: Our study showed the association of brachial-ankle pulse wave velocity with asymptomatic intracranial arterial stenosis in hypertension patients, especially in relative younger subjects. Brachial-ankle pulse wave velocity might be a relatively simple and repeatable measurement to detect hypertension patients in high risk of intracranial arterial stenosis.

Region-specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping.

In Parkinson's disease (PD), iron elevation in specific brain regions as well as selective loss of dopaminergic neurons is a major pathologic feature. A reliable quantitative measure of iron deposition is a potential biomarker for PD and may contribute to the investigation of iron-mediated PD. The primary purpose of this study is to assess iron variations in multiple deep grey matter nuclei in early PD with a novel MRI technique, quantitative susceptibility mapping (QSM). The inter-group differences of susceptibility and R2* value in deep grey matter nuclei, namely head of caudate nucleus (CN), putamen (PUT), global pallidus (GP), substantia nigra (SN), and red nucleus (RN), and the correlations between regional iron deposition and the clinical features were explored in forty-four early PD patients and 35 gender and age-matched healthy controls. Susceptibility values were found to be elevated within bilateral SN and RN contralateral to the most affected limb in early PD compared with healthy controls (HCs). The finding of increased susceptibility in bilateral SN is consistent with work on a subgroup of patients at the earliest clinical detectable state (Hoehn and Yahr [1967]: Neurology 17:427-442; Stage I). However, increased R2* values were only seen within SN contralateral to the most affected limb in the PD group when compared with controls. Furthermore, bilateral SN magnetic susceptibility positively correlated with disease duration and UPDRS-III scores in early PD. This finding supports the potential value of QSM as a non-invasive quantitative biomarker of early PD.

Breast Cancer: Diffusion Kurtosis MR Imaging-Diagnostic Accuracy and Correlation with Clinical-Pathologic Factors.

PURPOSE: To assess diagnostic accuracy with diffusion kurtosis imaging (DKI) in patients with breast lesions and to evaluate the potential association between DKI-derived parameters and breast cancer clinical-pathologic factors. MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. Data from 97 patients (mean age ± standard deviation, 45.7 years ± 13.1; range, 19-70 years) with 98 lesions (57 malignant and 41 benign) who were treated between January 2014 and April 2014 were retrospectively analyzed. DKI (with b values of 0-2800 sec/mm(2)) and conventional diffusion-weighted imaging data were acquired. Kurtosis and diffusion coefficients from DKI and apparent diffusion coefficients from diffusion-weighted imaging were measured by two radiologists. Student t test, Wilcoxon signed-rank test, Jonckheere-Terpstra test, receiver operating characteristic curves, and Spearman correlation were used for statistical analysis. RESULTS: Kurtosis coefficients were significantly higher in the malignant lesions than in the benign lesions (1.05 ± 0.22 vs 0.65 ± 0.11, respectively; P < .0001). Diffusivity and apparent diffusion coefficients in the malignant lesions were significantly lower than those in the benign lesions (1.13 ± 0.27 vs 1.97 ± 0.33 and 1.02 ± 0.18 vs 1.48 ± 0.33, respectively; P < .0001). Significantly higher specificity for differentiation of malignant from benign lesions was shown with the use of kurtosis and diffusivity coefficients than with the use of apparent diffusion coefficients (83% [34 of 41] and 83% [34 of 41] vs 76% [31 of 41], respectively; P < .0001) with equal sensitivity (95% [54 of 57]). In patients with invasive breast cancer, kurtosis was positively correlated with tumor histologic grade (r = 0.75) and expression of the Ki-67 protein (r = 0.55). Diffusivity was negatively correlated with tumor histologic grades (r = -0.44) and Ki-67 expression (r = -0.46). CONCLUSION: DKI showed higher specificity than did conventional diffusion-weighted imaging for assessment of benign and malignant breast lesions. Patients with grade 3 breast cancer or tumors with high expression of Ki-67 were associated with higher kurtosis and lower diffusivity coefficients; however, this association must be confirmed in prospective studies.

Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption.

Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection.

Collateral circulation prevents masticatory muscle impairment in rat middle cerebral artery occlusion model.

The rat suture middle cerebral artery occlusion (MCAO) is a frequently used animal model for investigating the mechanisms of ischemic brain injury. During suture MCAO, transection of the external carotid artery (ECA) potentially restrains blood flow and impairs masticatory muscle and other ECA-supported territories, consequently influencing post-operation animal survival. This study was aimed at investigating the effect of ECA transection on the hemodynamic alterations using a novel synchrotron radiation (SR) angiography technique and magnetic resonance imaging in live animals. Fifteen male adult Sprague-Dawley rats were used in this study. Animals underwent MCAO, in which the ECA was transected. SR angiography was performed before and after MCAO. Rats then underwent magnetic resonance imaging (MRI) to detect the tissue lesion both intra- and extra-cranially. Animals with SR angiography without other manipulations were used as control. High-resolution cerebrovascular morphology was analyzed using a novel technique of SR angiography. The masticatory muscle lesion was further examined by hematoxylin and eosin staining. MRI and histological results showed that there was no masticatory muscle lesion at 1, 7 and 28 days following MCAO with ECA transection. In normal condition, the ECA and its branch external maxillary artery were clearly detected. Following ECA transection, the external maxillary artery was still observed and the blood supply appeared from the anastomotic branch from the pterygopalatine artery. SR angiography further revealed the inter-relationship of hemisphere extra- and intra-cranial vasculature in the rat following MCAO. Transection of the ECA did not impair masticatory muscles in rat suture MCAO. Interrupted blood flow could be compensated by the collateral circulation from the pterygopalatine artery.

Spectral CT evaluation of interstitial brachytherapy in pancreatic carcinoma xenografts: preliminary animal experience.

OBJECTIVES: We sought to evaluate the capability of spectral CT to detect the therapeutic response to (125)I interstitial brachytherapy in a pancreatic carcinoma xenograft nude mouse model. METHODS: Twenty mice bearing SWl990 human pancreatic cancer cell xenografts were randomly separated into two groups: experimental (n = 10; 1.0 mCi) and control (n = 10; 0 mCi). After a two-week treatment, spectral CT was performed. Contrast-to-noise ratio (CNR) and iodine concentration (IC) in the lesions were measured and normalized to the muscle tissue, and nIC CD31 immunohistochemistry was used to measure microvessel density (MVD). The relationships between the nIC and MVD of the tumours were analysed. RESULTS: The nIC of the experimental group was significantly lower than that of the control group during the multiphase examination. A significant difference in the MVD was observed between the two groups (P <0.001). The nIC values of the three-phase scans have a certain positive correlation with MVD (r = 0.57, p < 0.0001; r = 0.48, p = 0.002; r = 0.63, p = 0.0017 in the 10, 25, and 60 s phase, respectively). CONCLUSIONS: Spectral CT can be a useful non-invasive imaging modality in evaluating the therapeutic effect of (125)I interstitial brachytherapy to a pancreatic carcinoma. KEY POINTS: Spectral CT offers opportunities to assess therapeutic response in pancreatic cancer cases. Spectral CT findings correlated with vascular changes associated with (125)I seed implantation. Spectral CT with monochromatic imaging removed most (125)I seed artefacts.

Contrast-enhanced multiphasic CT and MRI of primary hepatic pregnancy: a case report and literature review.

Primary hepatic pregnancy is extremely rare and difficult to diagnose radiologically. We present a 32-year-old woman with primary hepatic pregnancy diagnosed by using multi-modality imaging techniques, including ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI), which highlights diagnostic challenges. These techniques can define tissue planes in detail and identify embryo implantation into the hepatic parenchyma, thereby allowing accurate preoperative diagnosis and preoperative planning by the surgical team. To the best of our knowledge, this study is the first in the English literature to report a case of primary hepatic pregnancy, in which diffusion-weighted and contrast-enhanced multiphasic MRI were utilized for diagnosis and evaluation.

CT of the pancreas: comparison of image quality and pancreatic duct depiction among model-based iterative, adaptive statistical iterative, and filtered back projection reconstruction techniques.

The purpose of this study is to compare CT images of the pancreas reconstructed with model-based iterative reconstruction (MBIR), adaptive statistical iterative reconstruction (ASiR), and filtered back projection (FBP) techniques for image quality and pancreatic duct (PD) depiction. Data from 40 patients with contrast-enhanced abdominal CT [CTDIvol: 10.3 ± 3.0 (mGy)] during the late arterial phase were reconstructed with FBP, 40% ASiR-FBP blending, and MBIR. Two radiologists assessed the depiction of the main PD, image noise, and overall image quality using 5-point scale independently. Objective CT value and noise were measured in the pancreatic parenchyma, and the contrast-to-noise ratio (CNR) of the PD was calculated. The Friedman test and post-hoc multiple comparisons with Bonferroni test following one-way ANOVA were used for qualitative and quantitative assessment, respectively. For the subjective assessment, scores for MBIR were significantly higher than those for FBP and 40% ASiR (all P < 0.001). No significant differences in CT values of the pancreatic parenchyma were noted among FBP, 40% ASiR, and MBIR images (P > 0.05). Objective image noise was significantly lower and CNR of the PD was higher with MBIR than with FBP and 40% ASiR (all P < 0.05). Our results suggest that pancreatic CT images reconstructed with MBIR have lower image noise, better image quality, and higher conspicuity and CNR of the PD compared with FBP and ASiR.