Neuro-Signals
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In the past years, local field potential (LFP) signals recorded from the subthalamic nucleus (STN) in patients undergoing deep brain stimulation (DBS) for Parkinson's disease (PD) disclosed that DBS has a controversial effect on STN beta oscillations recorded 2-7 days after surgery for macroelectrode implantation. Nothing is known about these DBS-induced oscillatory changes 30 days after surgery. We recorded STN LFPs during ongoing DBS in 7 patients with PD, immediately (hyperacute phase) and 30 days (chronic phase) after surgery. ⋯ Power spectra of nuclei with significant beta activity (54% of the sample) showed that it decreased significantly during DBS (p=0.021) under both recording conditions. The time course of beta activity showed more evident DBS-induced changes in the chronic than in the hyperacute phase (p=0.014). DBS-induced changes in STN beta LFPs in patients undergoing DBS in chronic phase provide useful information for developing a new neurosignal-controlled adaptive DBS system.
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Reports suggest that microglia play a key role in spinal nerve ligation (SNL)-induced neuropathic pain, and toll-like receptor 3 (TLR3) has a substantial role in the activation of spinal microglia and the development of tactile allodynia after nerve injury. In addition, ketamine application could suppress microglial activation in vitro, and ketamine could inhibit proinflammatory gene expression possibly by suppressing TLR-mediated signal transduction. Therefore, the present study was designed to disclose whether intrathecal ketamine could suppress SNL-induced spinal microglial activation and exert some antiallodynic effects on neuropathic pain by suppressing TLR3 activation. ⋯ Furthermore, Western blot analysis displayed that ketamine application downregulated SNL-induced phosphorylated-p38 (p-p38) expression, which was specifically expressed in spinal microglia but not in astrocytes or neurons. Besides, ketamine could reverse TLR3 agonist (polyinosine-polycytidylic acid)-induced mechanical allodynia and spinal microglia activation. It was concluded that intrathecal ketamine depresses TLR3-induced spinal microglial p-p38 mitogen-activated protein kinase pathway activation after SNL, probably contributing to the antiallodynic effect of ketamine on SNL-induced neuropathic pain.
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Tert-butylhydroquinone (tBHQ) is a xenobiotic with reported antioxidant properties. tBHQ has been shown to induce nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2) to further activate the antioxidant response element (ARE). In turn, the Nrf2/ARE pathway is responsible for the induction of phase 2 antioxidant enzymes that detoxify oxidant promoters from different toxic insults. In this work, the antioxidant and protective actions of tBHQ were explored for the first time on different biomarkers of the neurotoxic model produced by the excitotoxic and pro-oxidant molecule quinolinic acid (QUIN) in rat striatal slices. ⋯ In addition, tBHQ enhanced glutathione-S-transferase activity, partially recovering its depletion induced by QUIN treatment. Our results also demonstrated that tBHQ was able to induce nuclear accumulation of Nrf2 and further antioxidant protection: while QUIN alone decreased the nuclear Nrf2, a treatment with tBHQ preserved the nuclear levels Nrf2 in the presence of QUIN. Therefore, the tBHQ-mediated Nrf2/ARE induction constitutes a signaling-mediated antioxidant strategy and therapeutic tool to be tested in different neurotoxic models.
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Recent experimental and theoretical data indicate that the functional capabilities of axons with specialized structures are much more diverse than traditionally thought. However, few observations were concerned with the main axons without arborization. In the present study, electrical stimulation of the saphenous nerve at different frequencies (2, 5, 10, 20 Hz) was used to test the role of activity-dependent effects on the pattern of action potentials that propagate along individual unmyelinated fibers (C fibers) within the trunk of the saphenous nerve in rabbits. ⋯ A novel fluctuation in interspike intervals was always observed immediately before the occurrence of the failures, implying that the fluctuation of conduction velocity is correlated with imminent failures. Both the 4-aminopyridine-sensitive potassium current and hyperpolarization-activated cation current were recognized to be involved in the regulation of conduction failure patterns. The results confirmed, at least in part, the existence of conduction failures in the main axon of C fibers, suggesting that axonal operations may also be determinants for adaptation phenomenon and information processing in peripheral nervous system.
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Akt has been implicated in pro-survival and anti-apoptotic activities in many cell types, including dorsal root ganglion (DRG) and spinal motor neurons. In this immunohistochemical study we have monitored phosphorylated Akt (p-Akt) levels in adult mouse DRGs and spinal cord following unilateral peripheral sciatic nerve transection (axotomy) or carrageenan-induced inflammation. In control animals around half of the lumbar DRG neuron profiles (NPs), mainly small and medium-sized ones, were p-Akt immunoreactive (IR), and of these around 50% expressed calcitonin gene-related peptide and/or isolectin IB4. ⋯ Carrageenan-induced peripheral inflammation increased the number of p-Akt-IR NPs after 1 h. Both axotomy and inflammation caused a clear increase in nuclear p-Akt-like immunoreactivity in DRG neurons. Our findings support a role for Akt as a key signaling molecule in sensory neurons and spinal cord after peripheral injury.