Imaging reveals the focal area of spreading depolarizations and a variety of hemodynamic responses in a rat microembolic stroke model

Spreading depolarizations (SDs) occur in stroke, but the spatial association between SDs and the corresponding hemodynamic changes is incompletely understood. We applied multimodal imaging to visualize the focal area of selected SDs, and hemodynamic responses with SDs propagating over the ischemic cortex. The intracarotid infusion of polyethylene microspheres (d=45 to 53 μm) produced multifocal ischemia in anesthetized rats (n=7). Synchronous image sequences captured through a cranial window above the frontoparietal cortex revealed: Changes in membrane potential (voltage-sensitive (VS) dye method); cerebral blood flow (CBF; laser speckle contrast (LSC) imaging); and hemoglobin (Hb) deoxygenation (red intrinsic optical signal (IOS) at 620 to 640 nm). A total of 31 SD events were identified. The foci of five SDs were seen in the cranial window, originating where CBF was the lowest (56.9±9%), but without evident signs of infarcts. The hyperemic CBF responses to propagating SDs were coupled with three types of Hb saturation kinetics. More accentuated Hb desaturation was related to a larger decrease in CBF shortly after ischemia induction. Microsphere-induced embolization triggers SDs in the rat brain, relevant for small embolic infarcts in patients. The SD occurrence during the early phase of ischemia is not tightly associated with immediate infarct evolution. Various kinetics of Hb saturation may determine the metabolic consequences of individual SDs.     

Links between oral health and personality at a law enforcement school

One of the territories of dental psychosomatics is the link between personality characterisctics and dental status. The aim of the present study was to survey the relationship between temperament and character factors and dental status in police students. It can be hypothesized, that some temperament factors can increase the risk for dental health problems. After dental screening 792 police students completed the Temperament and Character Inventory (TCI) devised by Cloninger. 57.5% of students rated their own teeth as being in good or very good condition, and only 2.8% as bad condition. In persons rating their dental status as “good”, the average DMFT was 9.23±5.01 (mean±S.D.). In students assessing their own oral health as bad, TCI results showed that a higher percentage of students displayed extravagance, impulsiveness, disorderliness than the overall population. Among the students with good self-assessment but bad teeth, there was a higher percentage of students displaying passivity, low assertiveness, and introversion. The temperament and character factors may have negative consequences for students in an institution which exposes them to high stress level. It may be useful to screen these students using subjective health questionnaires in order to permit more effective efforts to positive health behaviour.     

Word stress representations are language-specific: Evidence from event-related brain potentials

Understanding speech at the basic levels entails the simultaneous and independent processing of phonemic and prosodic features. While it is well-established that phoneme perception relies on language-specific long-term traces, it is unclear if the processing of prosodic features similarly involves language-specific representations. In the present study, we investigated the processing of a specific prosodic feature, word stress, using the method of event-related brain potentials (ERPs) employing a cross-linguistic approach. Hungarian participants heard disyllabic pseudowords stressed either on the first (legal stress) or on the second (illegal stress) syllable, pronounced either by a Hungarian or a German speaker. Results obtained using a data-driven ERP analysis methodology showed that all pseudowords in the deviant position elicited an Early Differentiating Negativity and a Mismatch Negativity component, except for the Hungarian pseudowords stressed on the first syllable. This suggests that Hungarian listeners did not process the native legal stress pattern as deviant, but the same stress pattern with a nonnative accent was processed as deviant. This implies that the processing of word stress was based on language-specific long-term memory traces.     

Pathogenesis and genetics of neural tube defects

After congenital heart defects neural tube defects (NTDs) is the second most prevalent congenital malformation among birth defects. The average rate of isolated NTDs is 1.4-2.0 per 1000 live births worldwide. The etiology of isolated (nonsyndromic) NTDs is believed to be the result of a combination of genetic predisposition and environmental factors. Over 80 genes believed to be engaged in the neurulations have been identified during the investigation and research of the mouse models. Despite exhaustive research efforts, now spanning several decades, little is known about the actual genetic mechanisms governing the primary events involved in neural tube closure (NTC).     

Optimization of spoiled gradient-echo phase imaging for in vivo localization of a focused ultrasound beam

The parameters of a spoiled gradient-echo (SPGR) pulse sequence have been optimized for in vivo localization of a focused ultrasound beam. Temperature elevation was measured by using the proton resonance frequency shift technique, and the phase difference signal-to-noise ratio (SNR_{δ ϕ}) was estimated in skeletal muscle and kidney cortex in 10 rabbits. Optimized parameters included the echo time equivalent to T^*₂of the tissue, the longest repetition time possible with a 20-s sonication, and the flip angle equivalent to the Ernst angle. Optimal SPGR phase imaging can detect a sonication beam with a peak phase difference of 0.55 radian, which corresponds to a temperature elevation of 7.3°C. The sonication beam can be localized within one voxel (0.6 × 0.6 × 5 mm³) at power levels that are below the threshold for thermal damage of the tissue.     

Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: Role of nitric oxide

Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1-100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor l-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of biglycan. This is the first demonstration that biglycan leads to cytoprotection against hypoxia/reoxygenation injury, and that this phenomenon is partially mediated by an NO-dependent mechanism.     

Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Modulation of cerebellar activities by acupuncture stimulation: evidence from fMRI study

Recent neuroimaging studies have revealed that acupuncture stimulation modulates human central nervous system including cerebral limbic/paralimbic and subcortical structures. Due to the wide and intricate connections with cerebrum, we hypothesized that anatomically specific areas in human cerebellum are also modulated by acupuncture stimulation beyond classical involvement of cerebellum in motor coordination. Functional MRI (fMRI) was used to investigate neural substrates responding to the acupuncture stimulation of Pericardium 6 (PC6, Neiguan), an acupoint relevant for the management of nausea including vestibular-related motion sickness. Sham stimulation near the acupoint and tactile stimulation on the skin of the acupoint were given as separate conditions. Psychophysical scores as well as the heart and respiratory rates were measured during each condition. Acupuncture manipulation on PC6, in comparison to the sham acupuncture and tactile stimulation conditions, selectively activated left superior frontal gyrus, anterior cingulate gyrus, and dorsomedial nucleus of thalamus. Acupuncture-specific neural substrates in cerebellum were also evident in declive, nodulus, and uvula of vermis, quadrangular lobule, cerebellar tonsil, and superior semilunar lobule. Negative MR signal changes, often seen during the acupuncture of analgesic points, were not observed in the present study. Our data suggest that cerebellum serves as important activation loci during the acupuncture stimulation of PC6, and clinical efficacy of PC6 may be mediated by the cerebellar vestibular neuromatrix.     

Structural maturation, cell proliferation and bioelectric activity in long-term slice-cultures of immature rat hippocampus

Explants of transverse slices of the 6-day-old rat hippocampus were grown in a serum-free medium for 2–14 days. Histology performed after various culturing periods demonstrated that these slices maintain a high degree of 3-dimensional organotypy,while undergoing growth and differentiation of the main cellular elements similar to that seen in vivo. Histological indications of continuing cell proliferation were verified by autoradiography showing a labelling of neuroblasts in the dentate gyrus and of glioblasts at the sites of gliogenesis observed in vivo. Spontaneous bioelectric activity and evoked potentials were recorded, both indicating the development of impulse generation and neuronal connectivity within the explant. Silver impregnation and electron microscopic studies lent further support for the presence of neuronal networks intrinsic to the hippocampus. These findings suggest that within the period studied the hippocampal slice cultures mature in a fashion similar to that seen in situ.