Bmc Neurosci
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Randomized Controlled Trial
Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α.
Tumor necrosis factor-alpha (TNF-α) is elevated early in injured brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-α antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of TNF-α. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-α expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-α was measured by Immunofluorescence staining. In addition, TNFα contents of ischemic cerebral homogenates was measured using commercial enzyme-linked immunosorbent assay kits. ⋯ This finding indicates that early microglia overproduction of TNF-α in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients.
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The cortical silent period (CSP) elicited by transcranial magnetic stimulation (TMS) is affected by changes in TMS intensity. Some studies have shown that CSP is shortened or prolonged by short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF), Those studies, however, used different TMS intensities to adjust the amplitude of the motor evoked potential (MEP). Therefore, it is unclear whether changes in CSP duration are induced by changes in TMS intensities or by SICI and ICF. The purpose of this study was to confirm the effects of muscle contractions and stimulus intensities on MEP amplitude and the duration of CSP induced by single-pulse TMS and to clarify the effects of SICI and ICF on CSP duration.MEP evoked by TMS was detected from the right first dorsal interosseous muscle in 15 healthy subjects. First, MEP and CSP were induced by single-pulse TMS with an intensity of 100% active motor threshold (AMT) at four muscle contraction levels [10%, 30%, 50%, and 70% electromyogram (EMG)]. Next, MEP and CSP were induced by seven TMS intensities (100%, 110%, 120%, 130%, 140%, 150%, and 160% AMT) during muscle contraction of 10% EMG. Finally, SICI and ICF were recorded at the four muscle contraction levels (0%, 10%, 30%, and 50% EMG). ⋯ We confirmed that CSP duration is affected by TMS intensity but not by the muscle contraction level. This study demonstrated that CSP is shortened with SICI, but it is not altered with ICF. These results indicate that after SICI, CSP duration is affected by the activity of inhibitory intermediate neurons that are activated by the conditioning SICI stimulus.
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Substantial experimental evidence supports that reactive species mediate secondary damage after traumatic spinal cord injury (SCI) by inducing oxidative stress. Removal of reactive species may reduce secondary damage following SCI. This study explored the effectiveness of a catalytic antioxidant - Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP) - in removing reactive oxygen species (ROS), reducing oxidative stress, and improving functional recovery in vivo in a rat impact SCI model. The efficiency of MnTBAP was also compared with that of methylprednisolone - the only drug used clinically in treating acute SCI. ⋯ This study demonstrated for the first time in vivo and in vitro that MnTBAP significantly reduced the levels of SCI-elevated ROS and that MnTBAP is superior to methylprednisolone in removing ROS. Removal of ROS by MnTBAP significantly reduced protein nitration and membrane lipid peroxidation in neurons. MnTBAP more effectively reduced neurological deficits than did methylprednisolone after SCI - the first most important criterion for assessing SCI treatments. These results support the therapeutic potential of MnTBAP in treating SCI.
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Early optimization in finger dexterity of skilled pianists: implication of transcranial stimulation.
It has been shown that non-invasive transcranial direct current stimulation (tDCS) facilitates motor functions in healthy adults and stroke patients. However, little is known about neuroplastic changes induced by tDCS in highly-trained individuals. Here we addressed this issue by assessing the effect of tDCS on dexterity of finger movements in healthy adult pianists. Twelve pianists practiced bimanual keystrokes in an in-phase manner while bilateral tDCS (left anodal/right cathodal or vice versa) of the primary motor cortex was performed. Before and after stimulation, each participant was asked to perform the trained successive keystrokes, and to repetitively strike a key with each of the fingers as fast and accurate as possible while keeping the remaining fingers immobilized voluntarily. ⋯ These findings, in combination with lack of any correlation between the age at which pianists commenced the training and motor improvements for sham stimulation conditions, supports the idea that selectively late-started players benefit from tDCS, which we interpret as early optimization of neuroplasticity of the motor system.
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Upregulation of vasoconstrictor receptors in cerebral arteries, including endothelin B (ETB) and 5-hydroxytryptamine 1B (5-HT(1B)) receptors, has been suggested to contribute to delayed cerebral ischemia, a feared complication after subarachnoid hemorrhage (SAH). This receptor upregulation has been shown to be mediated by intracellular signalling via the mitogen activated protein kinase kinase (MEK1/2)--extracellular regulated kinase 1/2 (ERK1/2) pathway. However, it is not known what event(s) that trigger MEK-ERK1/2 activation and vasoconstrictor receptor upregulation after SAH.We hypothesise that the drop in cerebral blood flow (CBF) and wall tension experienced by cerebral arteries in acute SAH is a key triggering event. We here investigate the importance of the duration of this acute CBF drop in a rat SAH model in which a fixed amount of blood is injected into the prechiasmatic cistern either at a high rate resulting in a short acute CBF drop or at a slower rate resulting in a prolonged acute CBF drop. ⋯ Our findings suggest a series of events where 1) the acute CBF drop triggers early MEK-ERK1/2 activation, which 2) triggers the transcriptional upregulation of vasoconstrictor receptors in cerebral arteries during the following days, where 3) the resulting enhanced cerebrovascular contractility contribute to delayed cerebral ischemia.