A novel variable transformer-matched circuit was designed, developed, and tested for Sodium-23 Magnetic Resonance Imaging (MRI) of the rat brain. Sodium-23 MRI signal is approximately 20000 times lower than commonly used hydrogen-1 MRI signal and therefore highly optimized resonance detectors promise to maximize the possible image resolution. Physiologically, sodium-23 nuclei accumulate in brain tissue with impaired viability, for instance after a vascular blockage of an artery supplying the brain. Developing highly optimized radio-frequency circuits for MRI is challenging as the large and strong static magnets only provide limited access to adjust circuits inside the scanner. However, adjustment is needed to compensate for various loss mechanisms due to circuit and tissue interaction. Common circuits use capacitive matching through commercially available trimmer capacitors. Alternatively, transformer-matching offers further reduced losses while it is challenging to mechanically vary the mutual inductance in practice. Here we propose to use a novel mechanical mechanism that translates a rotation of a rod from outside the scanner to a longitudinal shift of the inductive coupling coil relative to the tuned MRI resonance coil. By doing so the coupling factor between the two inductors can be stably varied and hence optimal 50Ω matching can be achieved. Superior Signal-to-Noise-Ratio of ~60 in ventricles and ~20 in tissue was recorded in volume elements of 0.5 x 0.5 x 2mm nominal resolution recorded in 5minutes using a gradient echo sequence. Most notably, the non-invasive measurement of the sodium-23 signal showed an increased intensity in ischemic tissue which may provide a promising measure to monitor cell viability in the future. We conclude that sodium-23 MRI at 9.4T benefits from an optimized resonant circuit for signal detection providing a promising tool to study metabolic and ion concentration related changes after stroke non-invasively with sufficient spatial and temporal resolution.Clinical Relevance— This report presents superior image resolution for sodium-23 Magnetic Resonance Imaging of a rat stroke model that may enable to monitor tissue viability faster and with higher resolution aiding development of new treatment strategies.
This study aims to determine the effects of diabetes in the retinal and brain microvasculature through gene expression profiling. Twelve male Wistar rats were randomly divided into two groups: streptozotocin-induced diabetic rats and time-matched nondiabetic rats. The retinal microvessels (RMVs) and brain microvessels (BMVs) were mechanically isolated from individual rats. Differentially expressed genes (DEGs) in diabetic and nondiabetic microvessels were identified by cDNA microarrays analysis. In RMVs, we identified 43 DEGs, of which 20 were upregulated while 23 were downregulated by diabetes. In BMVs, 35 genes DEGs were identified, of which 22 were upregulated and 13 were downregulated by diabetes. Altered expression of the Nars, Gars, Mars, Iars, Yars, Bcl2, Nqo1, NR4A3, Gpd1, Stc1, Tsc22d3, Tnfrsf21 mRNA as observed in the microarray analyses, was confirmed by quantitative RT-PCR. The aminoacyl-tRNA synthetases (aaRSs) pathway in RMVs was significantly overrepresented as compared to BMVs. Our study demonstrates for the first time that in the brain microvasculature multiple compensatory mechanisms exists, serving to protect brain tissue from diabetic insults, whereas these mechanisms are not activated in the retinal microvasculature. This provides new insights as to why brain microvasculature is less susceptible to diabetes.
Objective It is well known that the use of shift reagents (SRs) in nuclear magnetic resonance (NMR) studies is substantially limited by an intact blood–brain barrier (BBB). The current study aims to develop a method enabling chemical shift imaging in the living rat brain under physiological conditions using an SR, Tm[DOTP] 5− . Materials and methods Hyperosmotic mannitol bolus injection followed by 60 min infusion of a Tm[DOTP] 5− containing solution was administered via a catheter inserted into an internal carotid artery. We monitored the homeostasis of physiological parameters, and we measured the thulium content in brain tissue post mortem using total reflection fluorescence spectroscopy (T-XRF). The alterations of the 23 Na resonance spectrum were followed in a 9.4T small animal scanner. Results Based on the T-XRF measurements, the thulium concentration was estimated at 2.3 ± 1.8 mM in the brain interstitial space. Spectroscopic imaging showed a split of the 23 Na resonance peak which became visible 20 min after starting the infusion. Chemical shift imaging revealed a significant decrease of the initial intensity level to 0.915 ± 0.058 at the end of infusion. Conclusion Our novel protocol showed bulk accumulation of Tm[DOTP] 5− thus enabling separation of the extra-/intracellular 23 Na signal components in the living rat brain while maintaining physiological homeostasis.
Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural collections of blood and its products exerting merely a mass effect on the underlying brain. During the last decades, however, new insights into the pathogenetic mechanisms urge us to reconsider such a simplistic view. Here, we critically review novel pathophysiological, imaging, interventional, and medical treatment aspects and establish an integrative concept of the pathogenesis of CSH stressing the role of age as key factor. Trauma is considered a trigger event that unleashes a cascade of immunological and angiogenic age-dependent responses. These are associated with hypervascularization of the outer hematoma membrane, rebleeding, and exsudation which are crucial determinants for further development and propagation of CSH. Neurosurgical evacuation of the hematoma has long been thought the only viable treatment option, and it is still the method of choice in the majority of cases. Only more recently, embolization of the middle meningeal artery has been introduced as an alternative to surgery, and pharmacological treatment options are being investigated. Persons with advanced age trauma and other trigger events encounter a repair system with characteristics of senescence. This repair system implies a dysfunctional secretory phenotype of senescent cells and results in an insufficient repair process including chronic inflammation and fibrosis. Increased knowledge about the pathomechanisms of CSH will inform future studies and open new perspectives for its treatment and possibly also for its prevention.
Although retinal microvessels (RMVs) and brain microvessels (BMVs) are closely related in their developmental and share similar blood-neural barriers, studies have reported markedly different responses to stressors such as diabetes. Therefore, we hypothesized that RMVs and BMVs will display substantial differences in gene expression levels even though they are of the same embryological origin. In this study, both RMVs and BMVs were mechanically isolated from rats. Full retinal and brain tissue samples (RT, BT) were collected for comparisons. Total RNA extracted from these four groups were processed on Affymetrix rat 2.0 microarray Chips. The transcriptional profiles of these tissues were then analyzed. In the present paper we looked at differentially expressed genes (DEGs) in RMVs (against RT) and BMVs (against BT) using a rather conservative threshold value of ≥ ± twofold change and a false discovery rate corrected for multiple comparisons (p < 0.05). In RMVs a total of 1559 DEGs were found, of which 1004 genes were higher expressed in RMVs than in RT. Moreover, 4244 DEGs between BMVs and BT were identified, of which 1956 genes were ≥ twofold enriched in BMVs. Using these DEGs, we comprehensively analyzed the actual expression levels and highlighted their involvement in critical functional structures in RMVs and BMVs, such as junctional complex, transporters and signaling pathways. Our work provides for the first time the transcriptional profiles of rat RMVs and BMVs. These results may help to understand why retina and brain microvasculature show different susceptibilities to stressors, and they might even provide new insight for pharmacological interventions.
Einleitung Softdrinks leisten einen erheblichen Beitrag zur täglichen Kalorien- und Zuckeraufnahme - insbesondere für Kinder und Jugendliche. Deswegen drängt u.a. die WHO aktuell darauf, die Determinanten des Softdrinkkonsums besser zu untersuchen. Hierzu legen wir den ersten systematischen Review vor.
Ziel der Arbeit war die Ermittlung bundesweiter Repräsentativdaten zur Nutzung von Sonnenbrillen an sonnigen Sommertagen in Freizeit und Beruf und die Identifizierung von Bevölkerungs- und Berufsgruppen, bei denen diese Präventionsmaßnahme sonnenbedingter Augenschäden besonders defizitär ist. Im bundesweit repräsentativen Nationalen Krebshilfe-Monitoring wurden in der Welle 2015 3000 Personen zwischen 14 und 45 Jahren zu ihrer Sonnenbrillennutzung in der Freizeit sowie in der Welle 2016 485 Außenarbeiter zwischen 14 und 45 Jahren zu ihrer Sonnenbrillennutzung im Beruf befragt. Zusammenhänge zwischen der Sonnenbrillennutzung und soziodemografischen Eigenschaften wurden mittels χ2-Test untersucht. Zusätzlich wurden die Zusammenhänge der Sonnenbrillennutzung im Beruf und den jeweiligen Berufsgruppen mittels deskriptiver und bivariater Methoden abgebildet. Während mehr als die Hälfte der Normalbevölkerung an einem sonnigen Sommertag oft oder immer eine Sonnenbrille trägt, tun dies nur rund ein Drittel der Außenbeschäftigten. Während etwa jeder siebte Befragte in seiner Freizeit nie eine Sonnenbrille trägt, ist es unter Außenbeschäftigten jeder Dritte. Die Nutzung in der Freizeit steigt mit zunehmendem Alter. Ein Ansatzpunkt zur Erhöhung der Sonnenbrillennutzung im Beruf ist die gezielte Aufklärung hinsichtlich UV-bedingter Augenschäden durch Augen- und Betriebsärzte mit Unterstützung der Unfallversicherungsträger und der Arbeitgeber. Für präventive Maßnahmen bedeutsam erscheinen beispielsweise die Berufsgruppen der Gärtner, Landwirte und Maurer, welche allesamt stark UV-exponiert sind und gleichzeitig selten Sonnenbrillen tragen.
AIMS:The recent identification of acid sensing ion channels (ASICs) in vascular beds suggests their possible involvement in modulating vasomotor tone. Therefore, we investigated the gene expression profiles of ASIC subtypes in the middle cerebral artery (MCA) of Wistar rats and the functional implication of ASICs in acidosis-induced relaxation as well as maintenance of resting tension.MAIN METHODS:Real time PCR was employed to study the pattern of ASIC mRNA expression in the MCA wall in comparison with (i) matching brain tissue samples and (ii) arteries cultured for 24 h and 48 h. The functional implication regarding vasomotor response to acidosis and maintenance of resting tension was assessed using in vitro myography.KEY FINDINGS:A robust mRNA expression of ASIC-1, -2 and -4 was found in brain tissue samples and to a lower extent in freshly isolated MCA. In the MCA wall, short term culture induced a down-regulation of ASIC-1 and -2 expression without any remarkable change in ASIC-4 expression. Acidosis induced a pH-related relaxation of freshly isolated MCA ring segments, being more pronounced after short term culture. Incubation with the ASIC blocker amiloride moderately enhanced acidosis-induced relaxation, in cultured MCAs somewhat stronger than in freshly isolated vessels. In addition, amiloride resulted in a decrease of resting tension, albeit only in freshly isolated MCA.SIGNIFICANCE:Our results comprehensively describe ASIC subtype composition in the rat MCA in physiological and pathological conditions and strongly suggest the involvement of ASICs in the modulation of vasomotor responses under conditions of normal or decreased pH values.
OBJECTIVE:This study aimed at collecting representative national data on the use of sunglasses on sunny summer days during leisure time or work as well as identifying population and professional groups with a pronounced lack of preventive measures to avoid sun-induced eye damage. MATERIAL AND METHODS:Within the representative National Cancer Aid Monitoring, data on the use of sunglasses during leisure time was assessed among 3000 individuals aged 14-45 years in 2015, as well as on the use during outdoor work among 485 workers aged 14-45 years in 2016. Associations between the use of sunglasses and sociodemographic characteristics were assessed with the χ2-test. Additionally, descriptive and bivariate methods were used to assess connections between the use of sunglasses at work and each professional group. RESULTS:While more than half of the general population normally or often wear sunglasses on a sunny summer day, only one third of outdoor workers do so. While approximately every seventh individual surveyed never wears sunglasses during leisure time, among outdoor workers it is one out of three. The use during leisure time increases with age. DISCUSSION:Use of sunglasses during work could be supported by targeted information on UV-induced eye damage by ophthalmologists and company physicians with additional support from accident insurances and employers. Concerning preventive measures occupational groups such as landscapers, farmers and bricklayers who are strongly exposed to sunlight but rarely wear sunglasses are important groups.
In Deutschland raucht noch immer etwa jede fünfte junge Frau Tabakzigaretten. Gleichzeitig erfreuen sich E-Zigaretten auch in Deutschland insbesondere unter jungen Erwachsenen zunehmender Beliebtheit. Maternaler Nikotinkonsum birgt schwerwiegende Risiken für die Schwangere und das Kind. Das Ziel dieser Studie war es, den Konsum von Tabak- und E-Zigaretten sowie die Risikowahrnehmung bezüglich E-Zigaretten unter Schwangeren zu erfassen.
Der Mensch neigt in der Regel dazu, sich selbst als weniger anfällig für Krankheiten und die Folgen von Risikoverhaltensweisen zu sehen als Vergleichspersonen. Diese verzerrte Wahrnehmung bezeichnet man als unrealistischen komparativen Optimismus. Die subjektive Wahrnehmung des Erkrankungsrisikos steht nachgewiesenermaßen in starkem Zusammenhang mit dem gezeigten Risiko- und Gesundheitsverhalten. Das Ziel unserer Untersuchung war es, erstmals unrealistischen komparativen Optimismus in Bezug auf Hautkrebs repräsentativ zu untersuchen. Die Ergebnisse können wichtige Informationen für zukünftige Präventionsmaßnahmen liefern.
Alterations in the retinal microvessel (RMV) compartment occurring in systemic disease states such as diabetes may eventually contribute to blindness. To specifically address the pathophysiological role of the microvasculature we developed a new method for RMV bulk isolation from individual rats. The extraction procedure performed in the cold throughout takes less than one hour. Slight modifications enable isolation of brain microvessels (BMVs) for comparison. Microscopically, RMVs and BMVs consisted mainly of capillaries of good structural integrity. The endothelial cell/pericyte ratio was approximately 1.8 in RMVs and 2.7 in BMVs, well in agreement with data from intact vascular beds. Total RNA extracted from individual rats amounted to approximately 7 ng in RMVs, 50 ng in BMVs, and 155 ng in pial arteries (which were also isolated) with highly preserved integrity throughout. Measurements using microfluidic card methodology revealed segregation of RMVs, BMVs, and pial arteries in distinct clusters based on principal component analysis. In all three vascular compartments endothelial cell-specific markers were significantly enriched. Similarly, pericyte-specific markers displayed accumulation in RMVs, BMVs, and pial arteries, the latter probably reflecting the common ontogenetic origin of pericytes and smooth muscle cells. Isolation of RMVs, BMVs, and pial arteries from rats suffering from 8-weeks hyperglycemia yielded expression patterns of endothelial cell- and pericyte-specific marker genes largely comparable to those obtained in control rats. Our newly developed protocols allow for selective studies of RMVs from individual rats to characterize reactive pathways, in comparison with the ontogenetically closely related BMVs. Moreover, our protocols with inclusion of pial arteries enable comparative studies of the macro- and microvasculature from the same organ.
Die Steigerung der eigenen Attraktivität gilt als ein Hauptgrund für das Bräunen durch natürliche und künstliche ultraviolette (UV) Strahlung. Bisher wurde die Bedeutung der attraktivitätsbezogenen Motive jedoch nur in hochselektiven Stichproben untersucht und meist nur durch einzelne Items erfasst. Wir haben den Zusammenhang zwischen attraktivitätsbezogenen Motiven der UV-Exposition und diesbezüglichem Risikoverhalten und -wahrnehmung in einer bundesweit repräsentativen Stichprobe untersucht.
Optical coherence tomography (OCT) is a clinical standard in ophthalmology. Currently, its application in dentistry is gaining increasing interest. In this study, we tested the possibility to use a modified commercially available spectral domain OCT (SD-OCT) to assess the layer thickness of orthodontic surface sealants.
Focal brain ischemia markedly affects cerebrovascular reactivity. So far, these changes have mainly been related to alterations in the level of smooth muscle cell function while alterations of the endothelial lining have not yet been studied in detail. We have, therefore, investigated the effects of ischemia/reperfusion injury on bradykinin (BK)-induced relaxation since BK is an important mediator of tissue inflammation and affects vascular function in an endothelium-dependent manner. Focal brain ischemia was induced in rats by endovascular filament occlusion (2h) of the middle cerebral artery (MCA). After 22h reperfusion, both MCAs were harvested and the response to BK studied in organ bath experiments. Expression of the BK receptor subtypes 1 and 2 (B1, B2) was determined by real-time semi-quantitative RT-qPCR methodology, and whole mount immunofluorescence staining was performed to show the B2 receptor protein expression. In control animals, BK did not induce significant vasomotor effects despite a functionally intact endothelium and robust expression of B2 mRNA. After ischemia/reperfusion injury, BK induced a concentration-related sustained relaxation in all arteries studied, more pronounced in the ipsilateral than in the contralateral MCA. The B2 mRNA was significantly upregulated and the B1 mRNA displayed de novo expression, again more pronounced ipsi- than contralaterally. Endothelial cells displaying B2 receptor immunofluorescence were observed scattered or clustered in previously occluded MCAs. Relaxation to BK was mediated by B2 receptor activation, abolished after endothelium denudation, and largely diminished by blocking nitric oxide (NO) release or soluble guanylyl cyclase activity. Relaxation to BK was partially inhibited by charybdotoxin (ChTx), but not apamin or iberiotoxin suggesting activation of an endothelium-dependent hyperpolarization pathway. When the NO-cGMP pathway was blocked, BK induced a transient relaxation which was suppressed by ChTx. After ischemia/reperfusion injury BK elicits endothelium-dependent relaxation which was not detectable in control MCAs. This gain of function is mediated by B2 receptor activation and involves the release of NO and activation of an endothelium-dependent hyperpolarization. It goes along with increased B2 mRNA and protein expression, leaving the functional role of the de novo B1 receptor expression still open.