Bmc Neurosci
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Anesthetics dose-dependently shift electroencephalographic (EEG) activity towards high-amplitude, slow rhythms, indicative of a synchronization of neuronal activity in thalamocortical networks. Additionally, they uncouple brain areas in higher (gamma) frequency ranges possibly underlying conscious perception. It is currently thought that both effects may impair brain function by impeding proper information exchange between cortical areas. But what happens at the local network level? Local networks with strong excitatory interconnections may be more resilient towards global changes in brain rhythms, but depend heavily on locally projecting, inhibitory interneurons. As anesthetics bias cortical networks towards inhibition, we hypothesized that they may cause excessive synchrony and compromise information processing already on a small spatial scale. Using a recently introduced measure of signal independence, cross-approximate entropy (XApEn), we investigated to what degree anesthetics synchronized local cortical network activity. We recorded local field potentials (LFP) from the somatosensory cortex of three rats chronically implanted with multielectrode arrays and compared activity patterns under control (awake state) with those at increasing concentrations of isoflurane, enflurane and halothane. ⋯ The results suggest that anesthetics strongly diminish the independence of operation of local cortical neuronal populations, and that the quantification of these effects in terms of XApEn has a similar discriminatory power as changes of spontaneous action potential rates. Thus, XApEn of field potentials recorded from local cortical networks provides valuable information on the anesthetic state of the brain.
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Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP) at present. In this connection, 10% hypertonic saline (HS) alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol. ⋯ We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.
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Apolipoprotein-E (apoE) plays important roles in neurobiology and the apoE4 isoform increases risk for Alzheimer's disease (AD). ApoE3 and apoE2 are known to form disulphide-linked dimers in plasma and cerebrospinal fluid whereas apoE4 cannot form these dimers as it lacks a cysteine residue. Previous in vitro research indicates dimerisation of apoE3 has a significant impact on its functions related to cholesterol homeostasis and amyloid-beta peptide degradation. The possible occurrence of apoE dimers in cortical tissues has not been examined and was therefore assessed. Human frontal cortex and hippocampus from control and AD post-mortem samples were homogenised and analysed for apoE by western blotting under both reducing and non-reducing conditions. ⋯ The identification of disulphide-linked apoE dimers in human cortical and hippocampal tissues represents a distinct structural difference between the apoE3 and apoE4 isoforms that may have functional consequences.
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Transplantation of oligodendrocyte precursor cells (OPCs) is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA) is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. ⋯ These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.
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Few methods exist to study central nervous system processes following dentoalveolar tactile stimulation using functional magnetic resonance imaging (fMRI), likely due to inherent technical difficulties. Our primary goal was to develop and perform feasibility testing of a novel device capable of delivering valid and reliable dentoalveolar stimuli at dental chair-side and during MRI. Details of a device designed to deliver dentoalveolar dynamic pressure stimuli are described. Device testing took place in three settings: a) laboratory testing to assess range of stimulus force intensities, b) dental chair-side to assess reliability, validity and discriminant ability in force-pain relationship; and c) MRI to evaluate magnetic compatibility and ability to evoke brain activation in painfree subjects similar to those described in the literature. ⋯ The organization of the trigeminal system is unique as it provides somatosensory innervation to the face, masticatory and oral structures, the majority of the intracranial contents 1 and to specialized structures (tongue, nasal mucosa, auricle, tympanic membrane, cornea and part of the conjunctiva) 2. Somatic sensory information transmitted by the trigeminal nerve is crucial for normal orofacial function; however, the mechanisms of many chronic pain conditions affecting areas innervated by this sensory system are not well understood 345. The clinical presentation of chronic intraoral pain in the area of a tooth or in a site formally occupied by a tooth with no clinical or radiological signs of pathology, referred to as atypical odontalgia (AO) 67, is one such chronic pain condition of particular interest to dentists that is difficult to diagnose and manage. Recent research suggests both peripheral and central nervous system mechanisms being involved in AO pathophysiology 8910, but the majority of mechanism-based research of patients with AO has focused on the "peripheral aspect" 7.Functional magnetic resonance imaging (fMRI) is an established research technique to study the central aspects of pain 11. Of existing neuroimaging techniques, fMRI provides good spatial resolution of cortical and subcortical structures critical in the processing of nociception, acceptable temporal resolution, does not involve ionizing radiation, and can be performed using most MRI systems that already exist in research centers and the community. For these reasons, we sought to develop a protocol that allows us to use this tool to investigate the central mechanisms involved in the processes of intraoral pain arising from the dentoalveolar region. Using this device, our long-term objective is to improve our understanding of the underlying mechanisms of persistent dentoalveolar pain.In the past few years several studies used fMRI to investigate the human trigeminal system 1213, with a limited subset focusing on intraoral stimulation - specifically on the dentoalveolar processes, such as lip, tongue and teeth stimulation 14 or only teeth 151617. Some reasons for scarce literature on this topic may be the technical challenges involved in delivering facial/intraoral stimulation inside a MR scanner 1718: possibility of magnetic interference, detriment of image quality, subject discomfort and reduced working space between the subject's head and the radiofrequency coil. As a consequence a MR-compatible device would need to not only overcome these challenges but also be capable of delivering a controlled and reproducible stimuli 19, as reliability/reproducibility is a necessary feature of sensory testing 20.Existing MR-compatible methods of dentoalveolar stimulation are limited and do not adequately deliver stimuli across a range of non-painful to painful intensities and/or cannot be adjusted to reach posterior aspects of the dentoalveolar region. Therefore our goal was to develop and test the feasibility of a device able to: 1) provide reliable and valid dentoalveolar stimuli, 2) deliver such stimulation within the restricted space of an MR head coil, 3) be compatible for use within an MR environment, and 4) produce brain activation in painfree controls consistent to those observed by others using fMRI.