Brain research
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Modulation of long-interval intracortical inhibition and the silent period by voluntary contraction.
Transcranial magnetic stimulation was used to examine the effect of voluntary contraction on the magnitude of long-interval intracortical inhibition (LICI) and the duration of the silent period in intrinsic hand muscles. The magnitude of LICI acting on the first dorsal interosseus (FDI) measured with a paired-pulse protocol with an inter-pulse interval of 100 ms decreased with increasing tonic level of voluntary abduction force generated by the index finger. LICI in abductor pollicis brevis (APB) decreased from the condition in which the index finger was at rest to the conditions in which it was abducted, whereas LICI in abductor digiti minimi (ADM) was unaffected by the level of index finger abduction. ⋯ The duration of the silent period (SP) in FDI decreased with the level of voluntary index finger abduction and increased with eliciting stimulus intensity. Within-subject correlations showed that the effects of voluntary drive on SP duration and motor-evoked potential amplitude did not covary, implying an indirect effect of voluntary drive on SP duration. It is proposed that whereas voluntary drive directly reduces the magnitude of slow-acting inhibition acting on the active movement representations and near neighbors, sensory feedback from the contracting muscle acts to limit its time course.
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A mechanical insult to the brain drastically alters the microenvironment as specific cell types become reactive in an effort to sequester severely damaged tissue. Although injury-induced astrogliosis has been investigated, the relationship between well-defined biomechanical inputs and acute astrogliotic alterations is not well understood. We evaluated the effects of strain rate on cell death and astrogliosis using a three-dimensional (3-D) in vitro model of neurons and astrocytes within a bioactive matrix. ⋯ Moderate rate deformation increased cell density, GFAP reactivity, and hypertrophic process density. High rate deformation resulted in increased GFAP reactivity; however, other astrogliotic alterations were not observed at this time-point. These results demonstrate that the mode and degree of astrogliosis depend on rate of deformation, demonstrating astrogliotic augmentation at sub-lethal injury levels as well as levels inducing cell death.
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Spinal cord stimulation (SCS) is used to relieve ischemic pain and improve peripheral blood flow in selected patients with peripheral arterial diseases. Our previous studies show that antidromic activation of transient receptor potential vanilloid-1 (TRPV1) containing sensory fibers importantly contributes to SCS-induced vasodilation. ⋯ While TRPV1, CGRP and NO are known to be localized in the same nerve terminals, our data indicate that SCS-induced vasodilation depends on CGRP release, but not NO release. NO, released from endothelial cells, may be associated with vascular smooth muscle relaxation and peripheral blood flow increase in response to SCS.
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In GAD65-knockout mice, lack of GAD65 expression was confirmed. The expression level of vesicular GABA transporter (VGAT) was upregulated, and no change in the synaptic vesicles (SV)-associated GAD67 was found. ⋯ Although both GAD65(-/-) SV reconstituted with either GAD65 or GAD67 could synthesize GABA from [3H] glutamate and transport this newly synthesized GABA into SV, the combined evidence suggests that GAD65 plays a major role in GABA transmission in normal physiological condition. However, GAD67 could serve this role under some pathological conditions.
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For optimal neuroprotection following transient perinatal hypoxia-ischaemia (HI), therapy should start before overt secondary energy failure and its irreversible neurotoxic cascade. Hypothermia is a promising neuroprotective intervention that also prolongs the therapeutic time window ("latent-phase"; the period between re-establishment of apparently normal cerebral metabolism after HI, and the start of secondary energy failure). The influences of HI severity on latent-phase duration and regional neuroprotection are unclear. Under normothermia and delayed whole-body cooling to 35 and 33 degrees C we aimed to assess relationships between HI severity and: (i) latent-phase duration; (ii) secondary-energy-failure severity; and (iii) neuronal injury 48 h following HI. ⋯ Latent-phase duration is inversely related to insult severity; latent-phase brevity may explain the apparently less effective neuroprotection following severe cerebral HI.