Neuroscience
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Glioblastoma multiforme (GBM) is among the most lethal of all human tumors. It is the most frequently occurring malignant primary brain tumor in adults. The current standard of care (SOC) for GBM is initial surgical resection followed by treatment with a combination of temozolomide (TMZ) and ionizing radiation (IR). ⋯ This was verified in all cell lines by western blot analysis. Furthermore, the combination of TMZ and GDC-0941 with or without IR reduced the levels of p-AKT and O6-methylguanine DNA methyltransferase (MGMT) in T98G cells. The results of this study suggest that the combination of TMZ, IR, and GDC-0941 is a promising choice for future treatments of GBM.
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Spinal cord stimulation (SCS) has been suggested as a therapeutic technique for treating patients with disorder of consciousness (DOC). Although studies have reported its benefits for patients, the underlying pathophysiological mechanisms remain unclear. The aim of this study was to measure the effects of SCS on the EEG of patients in a minimally conscious state (MCS), which would allow us to explore the possible workings underpinning of the approach. ⋯ The main findings of this study were that: (1) significantly altered relative power and synchronisation was found in delta and gamma bands after one SCS stimulation using 5Hz, 70Hz or 100Hz; (2) bicoherence showed that coupling within delta was significantly decreased after stimulation using 70Hz, while reduction of coupling between delta and gamma was found when using 5Hz and 100Hz. However, SCS of 20Hz, 50Hz and sham stimulation did not induce changes in any frequency band at any region. This study showed EEG evidence that SCS can modulate the brain function of MCS patients, speculatively by activating the formation-thalamus-cortex network.
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Language experience shapes encoding of pitch-relevant information at both brainstem and cortical levels of processing. Pitch height is a salient dimension that orders pitch from low to high. Herein we investigate the effects of language experience (Chinese, English) in the brainstem and cortex on (i) neural responses to variations in pitch height, (ii) presence of asymmetry in cortical pitch representation, and (iii) patterns of relative changes in magnitude of pitch height between these two levels of brain structure. ⋯ CPR amplitude increased and FFR amplitude decreased with increasing pitch height. Experience-dependent effects on CPR components vary as a function of neural sensitivity to pitch height within a particular temporal window (Na-Pb). Differences between the auditory brainstem and cortex imply distinct neural mechanisms for pitch extraction at both levels of brain structure.
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The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurons) and mouse arcuate nucleus (ARC) neurons. ⋯ Perforated patch and whole-cell recordings from mouse hypothalamic slices demonstrated that oleate hyperpolarized a subpopulation of ARC GE neurons by KATP activation. Additionally, in a separate small population of ARC neurons, oleate application or lowered glucose concentration caused membrane depolarization. In conclusion, oleate induces KATP-dependent hyperpolarization and inhibition of firing of a subgroup of GE hypothalamic neurons without altering cellular energy charge.
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A better understanding of BOLD responses stems from a better characterization of the brain's ability to metabolize glucose and oxygen. Non-invasive techniques such as functional magnetic resonance spectroscopy (fMRS) have thus been developed allowing for the reproducible assessment of metabolic changes during barrel cortex (S1BF) activations in rats. The present study aimed at further exploring the role of neurotransmitters on local and temporal changes in vascular and metabolic function in S1BF. fMRS and fMRI data were acquired sequentially in α-chloralose anesthetized rats during 32-min rest and trigeminal nerve stimulation periods. ⋯ Dynamic analysis of metabolite concentrations allowed estimating changes in cerebral metabolic rates of glucose (ΔCMRGlc) and oxygen (ΔCMRO2). Findings confirmed a prevalence of oxidative metabolism during prolonged S1BF activation. Habituation led to a significant BOLD magnitude decline as a function of time while both total ΔCMRGlc and ΔCMRO2 remained constant revealing adaptation of glucose and oxygen metabolisms to support ongoing trigeminal nerve stimulation.