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biochemical processes underlying post-stroke neuroprotection. The results suggest that mild exercise postconditioning might play a similar neuroprotective role as intensive exercise and could be an effective exercise strategy as well.The roles of the medial olivocochlear reflex (MOCR) in human hearing have been widely investigated but remain controversial. We reason that this may be because the effects of MOCR activation on cochlear mechanical responses can be assessed only indirectly in healthy humans, and the different methods used to assess those effects possibly yield different and/or unreliable estimates. One aim of this study was to investigate the correlation between three methods often employed to assess the strength of MOCR activation by contralateral acoustic stimulation (CAS). We measured tone detection thresholds (N = 28), click-evoked otoacoustic emission (CEOAE) input/output (I/O) curves (N = 18), and distortion-product otoacoustic emission (DPOAE) I/O curves (N = 18) for various test frequencies in the presence and the absence of CAS (broadband noise of 60 dB SPL). As expected, CAS worsened tone detection thresholds, suppressed CEOAEs and DPOAEs, and horizontally shifted CEOAE and DPOAE I/O curves to higher levels. However, the CAS effect on tone detection thresholds was not correlated with the horizontal shift of CEOAE or DPOAE I/O curves, and the CAS-induced CEOAE suppression was not correlated with DPOAE suppression. Only the horizontal shifts of CEOAE and DPOAE I/O functions were correlated with each other at 1.5, 2, and 3 kHz. A second aim was to investigate which of the methods is more reliable. The test-retest variability of the CAS effect was high overall but smallest for tone detection thresholds and CEOAEs, suggesting that their use should be prioritized over the use of DPOAEs. Many factors not related with the MOCR, including the limited parametric space studied, the low resolution of the I/O curves, and the reduced numbers of observations due to data exclusion likely contributed to the weak correlations and the large test-retest variability noted. These findings can help us understand the inconsistencies among past studies and improve our understanding of the functional significance of the MOCR.Major depressive disorder (MDD) is a debilitating mental illness affecting people worldwide. Although significant progress has been made in the development of therapeutic agents to treat this condition, fewer than half of all patients respond to currently available antidepressants, highlighting the urgent need for the development of new classes of antidepressant drugs. Here, we found that paeoniflorin (PF) produced rapid and sustained antidepressant-like effects in multiple mouse models of depression, including the forced swimming test and exposure to chronic mild stress (CMS). Moreover, PF decreased the bodyweight of mice without affecting food intake and glucose homeostasis, and also reduced the plasma levels of total ghrelin and the expression of ghrelin O-acyltransferase in the stomach; however, the plasma levels of ghrelin and the ghrelin/total ghrelin ratio were unaffected. Furthermore, PF significantly increased the expression of growth hormone secretagogue receptor 1 alpha (GHSR1α, encoded by the Ghsr gene) in the intestine, whereas the levels of GHSR1α in the brain were only marginally downregulated following subchronic PF treatment. Finally, the genetic deletion of Ghsr attenuated the antidepressant-like effects of PF in mice exposed to CMS. These results suggested that increased GHSR1α expression in the intestine mediates the antidepressant-like effects of PF. U0126 Understanding peripheral ghrelin/GHSR signaling may provide new insights for the screening of antidepressant drugs that produce fast-acting and sustained effects.For many peripheral neuro-modulation applications, the cuff electrode has become a preferred technology for delivering electrical current into targeted volumes of tissue. While basic cuffs with low spatial selectivity, having longitudinally arranged contacts, can be produced from relatively straightforward processes, the fabrication of more complex electrode configurations typically requires iterative design and clean-room fabrication with skilled technicians. Although facile methods for fabricating cuff electrodes exist, their inconsistent products have limited their adoption for rapid manufacturing. In this article, we report a fast, low-cost fabrication process for patterning of electrode contacts in an implantable peripheral nerve cuff. Using a laser cutter as we have prescribed, the designer can render precise contact geometries that are consistent between batches. This method is enabled by the use of silicone/carbon black (CB) composite electrodes, which integrate with the patterned surface of its substufacturing.
Clinical studies have shown that electroacupuncture (EA) alleviates chronic itch. Gastrin-releasing peptide receptor (GRPR) and dynorphin (DYN) in the spinal dorsal horn positively or negatively regulate itch, respectively. However, which frequency of EA is effective on relieving chronic itch and reducing the expression of GRPR, whether DYN-A in the spinal cord is involved in the underlying mechanism of the antipruritus effect of EA remains unknown.
The mixture of acetone and diethyl ether (11) [designated as AEW (acetone/diethyl ether and water) treatment] was used to induce the dry skin model of chronic itch. EA was applied to Quchi (LI11) and Hegu (LI4). Western blot was used to detect the expression of GRPR and DYN-A. Immunofluorescence was used to detect the expression of DYN-A.
The AEW administration induced remarkable spontaneous scratching, enhanced the expression of GRPR, and reduced the expression of DYN-A. Compared with the sham EA, 2 Hz EA, or 15 Hz EA group, 100 Hz EA was the most effective frequency for relieving chronic itch, reducing the expression of GRPR, and increasing the expression of DYN-A in the cervical dorsal horn. Furthermore, intraperitoneal injection of kappa opioid receptors (KORs) antagonist nor-Binaltorphimine dihydrochloride (nor-BNI) significantly reversed the effect of 100 Hz EA on the inhibition of both itching behavior and GRPR expression.
EA at 100 Hz is the most effective frequency that inhibits chronic itch and GRPR expression through activation of KORs in the spinal dorsal horn, which can effectively guide the clinical treatment and improve the antipruritic effect of acupuncture.
EA at 100 Hz is the most effective frequency that inhibits chronic itch and GRPR expression through activation of KORs in the spinal dorsal horn, which can effectively guide the clinical treatment and improve the antipruritic effect of acupuncture.This study adopted diffusion tensor imaging to detect alterations in the diffusion parameters of the white matter fiber in Alzheimer's disease (AD) and used quantitative susceptibility mapping to detect changes in magnetic susceptibility. However, whether the changes of susceptibility values due to excessive iron in the basal ganglia have correlations with the alterations of the diffusion properties of the white matter in patients with AD are still unknown. We aim to investigate the correlations among magnetic susceptibility values of the basal ganglia, diffusion indexes of the white matter, and cognitive function in patients with AD. Thirty patients with AD and nineteen healthy controls (HCs) were recruited. Diffusion indexes of the whole brain were detected using tract-based spatial statistics. The caudate nucleus, putamen, and globus pallidus were selected as regions of interest, and their magnetic susceptibility values were measured. Compared with HCs, patients with AD showed that there were significantly increased axial diffusivity (AxD) in the internal capsule, superior corona radiata (SCR), and right anterior corona radiata (ACR); increased radial diffusivity (RD) in the right anterior limb of the internal capsule, ACR, and genu of the corpus callosum (GCC); and decreased fractional anisotropy (FA) in the right ACR and GCC. The alterations of RD values, FA values, and susceptibility values of the right caudate nucleus in patients with AD were correlated with cognitive scores. Besides, AxD values in the right internal capsule, ACR, and SCR were positively correlated with the magnetic susceptibility values of the right caudate nucleus in patients with AD. Our findings revealed that the magnetic susceptibility of the caudate nucleus may be an MRI-based biomarker of the cognitive dysfunction of AD and abnormal excessive iron distribution in the basal ganglia had adverse effects on the diffusion properties of the white matter.Early- and late-onset Alzheimer's disease (AD) patients often exhibit distinct features. We sought to compare overall white matter connectivity and evaluate the pathological factors (amyloid, tau, and vascular pathologies) that affect the disruption of connectivity in these two groups. A total of 50 early- and 38 late-onset AD patients, as well as age-matched cognitively normal participants, were enrolled and underwent diffusion-weighted magnetic resonance imaging to construct fractional anisotropy-weighted white matter connectivity maps. [18F]-THK5351 PET, [18F]-Flutemetamol PET, and magnetic resonance imaging were used for the evaluation of tau and related astrogliosis, amyloid, and small vessel disease markers (lacunes and white matter hyperintensities). Cluster-based statistics was performed for connectivity comparisons and correlation analysis between connectivity disruption and the pathological markers. Both patient groups exhibited significantly disrupted connectivity compared to their control counterparts with distinct patterns. Only THK retention was related to connectivity disruption in early-onset AD patients, and this disruption showed correlations with most cognitive scores, while late-onset AD patients had disrupted connectivity correlated with amyloid deposition, white matter hyperintensities, and lacunes in which only a few cognitive scores showed associations. These findings suggest that the pathogenesis of connectivity disruption and its effects on cognition are distinct between EOAD and LOAD.Passive listening to music is associated with several psychological and physical benefits in both, healthy and diseased populations. In this fMRI study, we examined whether preferred music has effects on the functional connectivity within resting-state networks related to consciousness. Thirteen patients in unresponsive wakefulness syndrome (UWS) and 18 healthy controls (HC) were enrolled. Both groups were exposed to different auditory stimulation (scanner noise, preferred music, and aversive auditory stimulation). Functional connectivity was analyzed using a seed-based approach. In HC, no differences were found between the three conditions, indicating that their networks are already working at high level. UWS patients showed impaired functional connectivity within all resting-state networks. In addition, functional connectivity of the auditory network was modulated by preferred music and aversive auditory stimulation. Hence, both conditions have the potential to modulate brain activity of UWS patients.