Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI

© 2015 Elsevier Ltd. All rights reserved. Cortical spreading depression (CSD) is a phenomenon implicated in migraine with aura and associated with other neurological disorders (e.g. stroke, brain trauma). Current evidence points to the essential role of NMDA receptors in CSD mechanisms. However, the roles of multiple subunits of NMDA receptors expressed in neurons, glia and blood vessels in vivo, are little explored. Using BOLD fMRI of urethane anesthetized rats as an integrative CSD readout, we tested the involvement of different NMDA receptor subtypes in CSD induction and propagation. Rats were treated with a non-selective NMDA blocker (MK-801), NR2B antagonist (ifenprodil) or a NR2A selective antagonist (TCN-201). CSD was induced during fMRI scanning by application of KCl onto the cerebral cortex and fMRI data were collected by 9.4 T MRI. The non-specific NMDA antagonist MK-801 completely blocked CSD, which was not observed in the NR2A group where TCN-201 did not alter the CSD features. Unexpectedly, the NR2B specific antagonist ifenprodil largely promoted the initial negative phase of the BOLD CSD response, likely due to altered neurovascular coupling. Our data suggest key roles and differential involvement of NMDA receptor subtypes in CSD generation and propagation, highlighting an important role for the NR2B subtype

Fast vascular component of cortical spreading depression revealed in rats by blood pulsation imaging

Cortical spreading depression (CSD) is a slowly propagating wave of depolarization of neurons and glia and has a less characterized vascular component. CSD is a commonly used phenomenon to test new methods of live brain imaging. Application of a blood pulsations imaging (BPI) technique to study of CSD induced with high-potassium solution in rat cortex allowed us to visualize for the first time the novel vascular component of a CSD wave. In our study, this wave component propagated in the limited part of the cortex along the bow-shaped trajectory in sharp contrast with concentric development of CSD measured by concurrently applied optical intrinsic signal (OIS) imaging technique. It was associated with a significant increase of the blood pulsations amplitude (BPA), started with a delay of 20 to 90 s comparing to signal measured with OIS, and propagated 40% faster than OIS signal. These findings suggest that the BPA and slower change of the cerebral blood volume are not directly related to each other even though both characterize the same vascular system. Our study indicates that the BPI technique could be used for characterization of the new pulsatile vascular component of CSDs in animal models of migraine, stroke, and brain trauma. © Society of Photo-Optical Instrumentation Engineers

Associations between the time of conception and the shape of the lactation curve in early lactation in Norwegian dairy cattle

<p>Abstract</p> <p>Background</p> <p>This study was carried out to determine if an association exists between the shape of the lactation curve before it is influenced by the event of conception and the time from calving to conception in Norwegian dairy cattle. Lactation curves of Norwegian Red cows during 5 to 42 days in milk (DIM) were compared between cows conceiving between 43 and 93 DIM and cows conceiving after 93 DIM.</p> <p>Methods</p> <p>Data from 23,049 cows, represented by one lactation each, with 219,538 monthly test days were extracted from the Norwegian Dairy Herd Recording System, which represents 97% of all Norwegian dairy cows. Besides veterinary treatments, these records also included information on daily milk yield at monthly test days. The data were stratified by parity groups (1, 2, and 3 and higher) and time to conception periods (43-93 DIM and >93 DIM). The sample was selected using the following selection criteria: conception later than 42 DIM, calving season July to September, no records of veterinary treatment and the level of energy fed as concentrates between 8.69 and 12.83 MJ. The shape of the lactation curves were parameterized using a modified Wilmink-model in a mixed model analysis. Differences in the parameters of the lactation curves with different conception times were evaluated using confidence intervals.</p> <p>Results</p> <p>Lactation curves characterized by a low intercept and a steep ascending slope and a steep descending slope were associated with early conception across all parities. The peak milk yield was not associated with time of conception.</p> <p>Conclusions</p> <p>A practical application of the study results is the use of the shape of the lactation curve in future herd management. Groups of cows with impaired reproductive performance may be identified due to an unfavorable shape of the lactation curve. Monitoring lactation curves and adjusting the feeding strategy to adjust yield therefore may be useful for the improvement of reproductive performance at herd level.</p

Synthesis of ZnO nanoparticles by flame spray pyrolysis and characterisation protocol

There is uncertainty concerning the potential toxicity of zinc oxide (ZnO) nanoparticles, which may be attributed in part to a lack of understanding with regard to the physiochemical properties of the nanoparticles used in toxicological investigations. This paper reports the synthesis of a ZnO nanopowder by flame spray pyrolysis and demonstrates that the typically employed characterisation techniques such as specific surface area measurement and X-ray diffraction provide insufficient information on the sample, especially if it is intended for use in toxicity studies. Instead, a more elaborate characterisation protocol is proposed that includes particle morphology as well as detailed compositional analysis of the nanoparticle surface. Detailed transmission electron microscopy analysis illustrated the polydispersity within the sample: particles were elongated in the c-crystallographic direction, with average Ferret length ∼23 nm and Ferret width ∼14 nm. Dynamic light scattering (0.1 w/v% in deionised water, pH 7.4) revealed the particles were agglomerated with a modal secondary particle size of ∼1.5 μm. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy indicated the presence of carbonate and hydroxide impurities on the surface of the ZnO nanoparticles and an increase of such impurities was observed as the sample was aged, which might influence the nanoparticle dissolution and/or cellular uptake behaviour. These data will be utilised, in order to facilitate the interpretation and understanding of results from toxicological investigations using in vitro cell lines

A consensus protocol for functional connectivity analysis in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience

Involvement of NMDA receptor subtypes in cortical spreading depression in rats assessed by fMRI

© 2015 Elsevier Ltd. All rights reserved. Cortical spreading depression (CSD) is a phenomenon implicated in migraine with aura and associated with other neurological disorders (e.g. stroke, brain trauma). Current evidence points to the essential role of NMDA receptors in CSD mechanisms. However, the roles of multiple subunits of NMDA receptors expressed in neurons, glia and blood vessels in vivo, are little explored. Using BOLD fMRI of urethane anesthetized rats as an integrative CSD readout, we tested the involvement of different NMDA receptor subtypes in CSD induction and propagation. Rats were treated with a non-selective NMDA blocker (MK-801), NR2B antagonist (ifenprodil) or a NR2A selective antagonist (TCN-201). CSD was induced during fMRI scanning by application of KCl onto the cerebral cortex and fMRI data were collected by 9.4 T MRI. The non-specific NMDA antagonist MK-801 completely blocked CSD, which was not observed in the NR2A group where TCN-201 did not alter the CSD features. Unexpectedly, the NR2B specific antagonist ifenprodil largely promoted the initial negative phase of the BOLD CSD response, likely due to altered neurovascular coupling. Our data suggest key roles and differential involvement of NMDA receptor subtypes in CSD generation and propagation, highlighting an important role for the NR2B subtype