Felbamate produces antidepressant‐like actions in the chronic unpredictable mild stress and chronic social defeat stress models of depression

Felbamate is an anticonvulsant used in the treatment of epilepsy. In this study, we investigated the antidepressant‐like actions of felbamate in mice. The effects of felbamate were first assessed using the forced swimming test (FST) and tail suspension test (TST), and then investigated in the chronic unpredictable mild stress (CUMS) and chronic social defeat stress (CSDS) models of depression. The changes in the hippocampal brain‐derived neurotrophic factor (BDNF) signaling cascade after chronic stress and felbamate treatment were also examined. It was found that felbamate exhibited antidepressant‐like activities in the FST and TST without affecting the locomotor activity of mice. Felbamate was also effective in both the CUMS and CSDS models of depression. Moreover, felbamate administration fully restored the decreased hippocampal BDNF signaling pathway in both the CUMS‐stressed and CSDS‐stressed mice. Collectively, felbamate has antidepressant‐like actions in mice involving the hippocampal BDNF system.     

Look‐Locker FAIR TrueFISP for arterial spin labelling on mouse at 9.4 T

Pulsed arterial spin labelling remains a non‐invasive and highly used method for the study of rodent cerebral blood flow (CBF). Flow‐sensitive alternating inversion recovery (FAIR) is one of the most commonly used MR‐sequences for this purpose and exists with many different strategies to record the images. This study investigates Look‐Locker (LL) TrueFISP readout for FAIR as an alternative to the standard EPI readout, which is provided by the manufacturer. The aim was to show the improved image quality using TrueFISP and to verify the reproducibility of the determination of the cerebral blood flow values. The measurement of many inversion points also allowed to investigate the influence of the correct blood relaxation rate on the fit of the CBF data. For the LL‐FAIR TrueFISP an in‐house written method was created. The method was tested on a group of C57BL/6 mice at the field strength of 9.4 T. The results show CBF maps with less distortion than for EPI and the values found are in good agreement with the literature. A comparison of the CBF values found with EPI and LL‐TrueFISP shows very small differences, most being not significant. In conclusion, the method presented gives equivalent CBF maps in comparison to standard FAIR‐EPI. Both methods have the same measurement time. TrueFISP has the advantage to EPI of producing undistorted images over larger areas of the mouse brain. It is advisable to check the value of the blood relaxation rate by measurement or to estimate it as a fitting parameter.     

Hyperpolarized product selective saturating‐excitations for determination of changes in metabolic reaction rates in real‐time

Investigation of hyperpolarized substrate metabolism has been showing utility in real‐time determination of in‐cell and in vivo enzymatic activities. Intracellular reaction rates may vary during the course of a measurement, even on the very short time scales of visibility on hyperpolarized MR, due to many factors such as the availability of the substrate and co‐factors in the intracellular space. Despite this potential variation, the kinetic analysis of hyperpolarized signals typically assumes that the same rate constant (and in many cases, the same rate) applies throughout the course of the reaction as observed via the build‐up and decay of the hyperpolarized signals. We demonstrate here an acquisition approach that can null the need for such an assumption and enable the detection of instantaneous changes in the rate of the reaction during an ex vivo hyperpolarized investigation, (i.e. in the course of the decay of one hyperpolarized substrate dose administered to a viable tissue sample ex vivo). This approach utilizes hyperpolarized product selective saturating‐excitation pulses. Similar pulses have been previously utilized in vivo for spectroscopic imaging. However, we show here favorable consequences to kinetic rate determinations in the preparations used. We implement this acquisition strategy for studies on perfused tissue slices and develop a theory that explains why this particular approach enables the determination of changes in enzymatic rates that are monitored via the chemical conversions of hyperpolarized substrates. Real‐time changes in intracellular reaction rates are demonstrated in perfused brain, liver, and xenograft breast cancer tissue slices and provide another potential differentiation parameter for tissue characterization.