Bmc Neurosci
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Alzheimer disease is a multifactorial disorder characterized by the progressive deterioration of neuronal networks. The pathological hallmarks includes extracellular amyloid plaques and intraneuronal neurofibrillary tangles, but the primary cause is only partially understood. Thus, there is growing interest in developing agents that might target multiple mechanisms leading to neuronal degeneration. CHF5074 is a nonsteroidal anti-inflammatory derivative that has been shown to behave as a γ-secretase modulator in vitro and to inhibit plaque deposition and to reverse memory deficit in vivo in transgenic mouse models of Alzheimer's disease (AD). In the present study, the effects of a long-term (13-month) treatment with CHF5074 on indicators of brain functionality and neurodegeneration in transgenic AD mice (Tg2576) have been assessed and compared with those induced by a prototypical γ-secretase inhibitor (DAPT). ⋯ This comparative analysis revealed a profoundly diverse range of clinically relevant effects differentiating the multifunctional anti-inflammatory derivative CHF5074 from the γ-secretase inhibitor DAPT and highlighted unique mechanisms and potential targets that may be crucial for neuroprotection in mouse models of AD.
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The olfactory ensheathing cells (OECs) derived from olfactory bulb (OB) may improve motor function after transplantation in injured spinal cord. However, the effects of OEC transplantation on sensory function have not been reported yet. The purpose of this study is to investigate whether OEC transplantation could affect the sensory function and to analyze the underlying mechanism. ⋯ The transplantation of OECs may induce the noticeable pain hypersensitivity in rats after hemisected spinal cord injury, and the possible mechanism may be associated with the phosphorylation of ERK and the activated BDNF overexpression.
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The nociceptive withdrawal reflex (NWR) is a polysynaptic spinal reflex that induces complex muscle synergies to withdraw a limb from a potential noxious stimulus. Several studies indicate that assessment of the NWR is a valuable objective tool in relation to investigation of various pain conditions. However, existing methodologies for NWR assessment evaluate standard surface electromyography (sEMG) measured over just one muscle and do not consider the possible interference of crosstalk originating from adjacent active muscles. The present study had two aims: firstly, to investigate to which extent the presence of crosstalk may affect NWR detection using a standardized scoring criterion (interval peak z-score) that has been validated without taking crosstalk into consideration. Secondly, to investigate whether estimation of muscle fiber conduction velocity can help identifying the propagating and non-propagating nature of genuine reflexes and crosstalk respectively, thus allowing a more valid assessment of the NWR. ⋯ This study investigated the negative effect of electrical crosstalk during reflex detection and revealed that the use of a previously validated scoring criterion may result in poor specificity due to crosstalk. The excellent performance of the developed methodology in the presence of crosstalk shows that assessment of muscle fiber conduction velocity allows reliable detection of EMG crosstalk during reflex detection.
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The afferent projections from the auricular branch of the vagus nerve (ABVN) to the nucleus tractus solitaries (NTS) have been proposed as the anatomical basis for the increased parasympathetic tone seen in auriculo-vagal reflexes. As the afferent center of the vagus nerve, the NTS has been considered to play roles in the anticonvulsant effect of cervical vagus nerve stimulation (VNS). Here we proposed an "auriculo-vagal afferent pathway" (AVAP), by which transcutaneous auricular vagus nerve stimulation (ta-VNS) suppresses pentylenetetrazol (PTZ)-induced epileptic seizures by activating the NTS neurons in rats. ⋯ There existed an anatomical relationship between the ABVN and the NTS, which strongly supports the concept that ta-VNS has the potential for suppressing epileptiform activity via the AVAP in rats. ta-VNS will provide alternative treatments for neurological disorders, which can avoid the disadvantage of VNS.
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It has been shown that olfactory ensheathing glia (OEG) and Schwann cell (SCs) transplantation are beneficial as cellular treatments for spinal cord injury (SCI), especially acute and sub-acute time points. In this study, we transplanted DsRED transduced adult OEG and SCs sub-acutely (14 days) following a T10 moderate spinal cord contusion injury in the rat. Behaviour was measured by open field (BBB) and horizontal ladder walking tests to ascertain improvements in locomotor function. Fluorogold staining was injected into the distal spinal cord to determine the extent of supraspinal and propriospinal axonal sparing/regeneration at 4 months post injection time point. The purpose of this study was to investigate if OEG and SCs cells injected sub acutely (14 days after injury) could: (i) improve behavioral outcomes, (ii) induce sparing/regeneration of propriospinal and supraspinal projections, and (iii) reduce tissue loss. ⋯ These results show that transplantation of OEG and SCs in a sub-acute phase can improve anatomical outcomes after a contusion injury to the spinal cord, by increasing the number of spared/regenerated supraspinal fibers, reducing cavitation and enhancing tissue integrity. This provides important information on the time window of glial transplantation for the repair of the spinal cord.