Individuals classified clinically as having a motor-complete spinal cord injury (mcSCI) should lack voluntary motor function below their injury level. Neurophysiological assessments using electromyography (EMG) and transcranial magnetic stimulation (TMS), however, have demonstrated that persons with mcSCI retain limited cortical descending innervation and voluntary activation of muscles below their level of injury, including muscles of the trunk and lower limb. https://www.selleckchem.com/products/piperaquine-phosphate.html We explored the possibility of whether there is also preserved innervation of the pelvic floor muscles (PFM) in persons with mcSCI. The PFM are controlled by widespread cortical and subcortical areas and typically coactivated with trunk and gluteal muscles to maintain continence and regulate intra-abdominal pressure. Nine mcSCI and eight control subjects participated in this cross-sectional study. Surface EMG was used to record activity in the PFM. Data were recorded while participants attempted various maneuvers of the trunk and pelvis. We also applied TMS at incrementing levels of intensity over the primary motor cortex area to record motor evoked potentials (MEPs) in the PFM. When performing the maneuvers, activation of the PFM was possible in all controls and the majority of SCI participants. However, the PFM were only activated in the SCI participants during maneuvers that engaged other trunk muscles, however. MEP responses in the PFM were also elicited in all controls and SCI participants, but MEP response characteristics were significantly altered in the SCI group. Our results suggest that persons with mcSCI retain some residual innervation of the PFM after injury, possibly via indirect cortical descending pathways.Macroautophagy/autophagy is an intracellular degradative pathway that is often induced as a pro-survival process for cells under stress. A few recent reports establish the role of the glycogen metabolic pathway in neuronal cell survival in conditions such as oxidative stress and hypoxia, and the possible link between glycogen synthesis and autophagy induction. This commentary highlights the emerging role of GYS (glycogen synthase) in neuronal autophagy and stress response.Small molecule inhibitors of calcium-dependent proteases, calpains (CAPNs), protect against neurodegeneration induced by a variety of insults including excitotoxicity and spinal cord injury (SCI). Many of these compounds, however, also inhibit other proteases, which has made it difficult to evaluate the contribution of calpains to neurodegeneration. Calpastatin is a highly specific endogenous inhibitor of classical calpains, including CAPN1 and CAPN2. In the present study, we utilized transgenic **** that overexpress human calpastatin under the prion promoter (PrP-hCAST) to evaluate the hypothesis that calpastatin overexpression protects against excitotoxic hippocampal injury and contusive SCI. The PrP-hCAST organotypic hippocampal slice cultures showed reduced neuronal death and reduced calpain-dependent proteolysis (α-spectrin breakdown production, 145 kDa) at 24 h after N-methyl-D-aspartate (NMDA) injury compared with the wild-type (WT) cultures (n = 5, p less then 0.05). The PrP-hCAST **** (n = 13) displayed a significant improvement in locomotor function at one and three weeks after contusive SCI compared with the WT controls (n = 9, p less then 0.05). Histological assessment of lesion volume and tissue sparing, performed on the same animals used for behavioral analysis, revealed that calpastatin overexpression resulted in a 30% decrease in lesion volume (p less then 0.05) and significant increases in tissue sparing, white matter sparing, and gray matter sparing at four weeks post-injury compared with WT animals. Calpastatin overexpression reduced α-spectrin breakdown by 51% at 24 h post-injury, compared with WT controls (p less then 0.05, n = 3/group). These results provide support for the hypothesis that sustained calpain-dependent proteolysis contributes to pathological deficits after excitotoxic injury and traumatic SCI.Maintaining the integrity and function of the presynaptic neurotransmitter release apparatus is a demanding process for a post-mitotic neuron; the mechanisms behind it are still unclear. BSN (bassoon), an active zone scaffolding protein, has been implicated in the control of presynaptic macroautophagy/autophagy, a process we recently showed depends on poly-ubiquitination of synaptic proteins. Moreover, loss of BSN was found to lead to smaller synaptic vesicle (SV) pools and younger pools of the SV protein SV2. Of note, the E3 ligase PRKN/parkin appears to be involved in BSN deficiency-related changes in autophagy levels, as shRNA-mediated knockdown of PRKN counteracts BSN-deficiency and rescues decreased SV protein levels as well as impaired SV recycling in primary cultured neurons. These data imply that BSN and PRKN act in concert to control presynaptic autophagy and maintain presynaptic proteostasis and SV turnover at the physiologically required levels.Objective This investigation addressed the desirable source-airway interaction obtained with vocalization through a semi-occlusion at the mouth. The semi-occlusion was a flow-resistant tube of varying length and diameter. Method The methodology was strictly computational. Airway shapes resembling those obtained from magnetic resonance or computed tomography imaging were stylized. Supraglottal and subglottal acoustic impedances were calculated, from which inertagrams were plotted over a frequency range of 0-4000 Hz. The inertagrams predict which harmonics are likely to be strengthened. Results The combination of epilaryngeal airway narrowing and lengthening, a pharyngeal expansion, and an oral narrowing behind the tube produce the best overall inertagram for pitch glide exercises. This configuration supports harmonics of the source evenly over a range of 300-4000 Hz. Conclusions For clinical applications, theory predicts that the length of a tube or straw does not matter if the inner diameter is on the order of 3 mm or less. For wider open-ended tubes, greater length can compensate for the wider diameter for the beneficial inertance effect, but the desired steady pressure in the airways for vocal fold posturing cannot be maintained.
Individuals classified clinically as having a motor-complete spinal cord injury (mcSCI) should lack voluntary motor function below their injury level. Neurophysiological assessments using electromyography (EMG) and transcranial magnetic stimulation (TMS), however, have demonstrated that persons with mcSCI retain limited cortical descending innervation and voluntary activation of muscles below their level of injury, including muscles of the trunk and lower limb. https://www.selleckchem.com/products/piperaquine-phosphate.html We explored the possibility of whether there is also preserved innervation of the pelvic floor muscles (PFM) in persons with mcSCI. The PFM are controlled by widespread cortical and subcortical areas and typically coactivated with trunk and gluteal muscles to maintain continence and regulate intra-abdominal pressure. Nine mcSCI and eight control subjects participated in this cross-sectional study. Surface EMG was used to record activity in the PFM. Data were recorded while participants attempted various maneuvers of the trunk and pelvis. We also applied TMS at incrementing levels of intensity over the primary motor cortex area to record motor evoked potentials (MEPs) in the PFM. When performing the maneuvers, activation of the PFM was possible in all controls and the majority of SCI participants. However, the PFM were only activated in the SCI participants during maneuvers that engaged other trunk muscles, however. MEP responses in the PFM were also elicited in all controls and SCI participants, but MEP response characteristics were significantly altered in the SCI group. Our results suggest that persons with mcSCI retain some residual innervation of the PFM after injury, possibly via indirect cortical descending pathways.Macroautophagy/autophagy is an intracellular degradative pathway that is often induced as a pro-survival process for cells under stress. A few recent reports establish the role of the glycogen metabolic pathway in neuronal cell survival in conditions such as oxidative stress and hypoxia, and the possible link between glycogen synthesis and autophagy induction. This commentary highlights the emerging role of GYS (glycogen synthase) in neuronal autophagy and stress response.Small molecule inhibitors of calcium-dependent proteases, calpains (CAPNs), protect against neurodegeneration induced by a variety of insults including excitotoxicity and spinal cord injury (SCI). Many of these compounds, however, also inhibit other proteases, which has made it difficult to evaluate the contribution of calpains to neurodegeneration. Calpastatin is a highly specific endogenous inhibitor of classical calpains, including CAPN1 and CAPN2. In the present study, we utilized transgenic mice that overexpress human calpastatin under the prion promoter (PrP-hCAST) to evaluate the hypothesis that calpastatin overexpression protects against excitotoxic hippocampal injury and contusive SCI. The PrP-hCAST organotypic hippocampal slice cultures showed reduced neuronal death and reduced calpain-dependent proteolysis (α-spectrin breakdown production, 145 kDa) at 24 h after N-methyl-D-aspartate (NMDA) injury compared with the wild-type (WT) cultures (n = 5, p less then 0.05). The PrP-hCAST mice (n = 13) displayed a significant improvement in locomotor function at one and three weeks after contusive SCI compared with the WT controls (n = 9, p less then 0.05). Histological assessment of lesion volume and tissue sparing, performed on the same animals used for behavioral analysis, revealed that calpastatin overexpression resulted in a 30% decrease in lesion volume (p less then 0.05) and significant increases in tissue sparing, white matter sparing, and gray matter sparing at four weeks post-injury compared with WT animals. Calpastatin overexpression reduced α-spectrin breakdown by 51% at 24 h post-injury, compared with WT controls (p less then 0.05, n = 3/group). These results provide support for the hypothesis that sustained calpain-dependent proteolysis contributes to pathological deficits after excitotoxic injury and traumatic SCI.Maintaining the integrity and function of the presynaptic neurotransmitter release apparatus is a demanding process for a post-mitotic neuron; the mechanisms behind it are still unclear. BSN (bassoon), an active zone scaffolding protein, has been implicated in the control of presynaptic macroautophagy/autophagy, a process we recently showed depends on poly-ubiquitination of synaptic proteins. Moreover, loss of BSN was found to lead to smaller synaptic vesicle (SV) pools and younger pools of the SV protein SV2. Of note, the E3 ligase PRKN/parkin appears to be involved in BSN deficiency-related changes in autophagy levels, as shRNA-mediated knockdown of PRKN counteracts BSN-deficiency and rescues decreased SV protein levels as well as impaired SV recycling in primary cultured neurons. These data imply that BSN and PRKN act in concert to control presynaptic autophagy and maintain presynaptic proteostasis and SV turnover at the physiologically required levels.Objective This investigation addressed the desirable source-airway interaction obtained with vocalization through a semi-occlusion at the mouth. The semi-occlusion was a flow-resistant tube of varying length and diameter. Method The methodology was strictly computational. Airway shapes resembling those obtained from magnetic resonance or computed tomography imaging were stylized. Supraglottal and subglottal acoustic impedances were calculated, from which inertagrams were plotted over a frequency range of 0-4000 Hz. The inertagrams predict which harmonics are likely to be strengthened. Results The combination of epilaryngeal airway narrowing and lengthening, a pharyngeal expansion, and an oral narrowing behind the tube produce the best overall inertagram for pitch glide exercises. This configuration supports harmonics of the source evenly over a range of 300-4000 Hz. Conclusions For clinical applications, theory predicts that the length of a tube or straw does not matter if the inner diameter is on the order of 3 mm or less. For wider open-ended tubes, greater length can compensate for the wider diameter for the beneficial inertance effect, but the desired steady pressure in the airways for vocal fold posturing cannot be maintained.
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