Neuroscience
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We used an immortalized arachnoid cell line to test the arachnoid barrier properties and paracellular transport. The permeabilities of urea, mannitol, and inulin through monolayers were 2.9 ± 1.1 × 10(-6), 0.8 ± .18 × 10(-6), 1.0 ± .29 × 10(-6)cm/s. Size differential permeability testing with dextran clarified the arachnoidal blood-cerebrospinal fluid (CSF) barrier limit and established a rate of transcellular transport to be about two orders of magnitude slower than paracellular transport in a polyester membrane diffusion chamber. ⋯ Calcium modulated paracellular transport, but only selectively with the ion chelator, EDTA, and with disruption of intracellular stores. The blood-CSF barrier at the arachnoid is anatomically and physiologically different from the vascular-based blood-brain barrier, but is similarly subject to modulation. We describe the basic paracellular transport characteristics of this CSF "sink" of the brain which will allow for a better description of mass and constitutive balance within the intracranial compartment.
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We have demonstrated previously that nicotine affords neuroprotective and anti-inflammatory effects against intracerebral hemorrhage (ICH)-associated neuropathological changes. The present study was undertaken to clarify whether subtype-specific agonists of nicotinic acetylcholine receptors (nAChRs) could preserve tissue integrity in mouse ICH model in vivo. ICH was induced by unilateral injection of collagenase into the striatum of male C57BL/6 mice. ⋯ PNU-282987 decreased the number of activated microglia/macrophages accumulating in the perihematoma region at 3 days after ICH, in a dose-dependent manner. On the other hand, the number of microglia/macrophages in the central region of hematoma at early phase of pathology (6 h after ICH) was increased by 10mg/kg PNU-282987. These results suggest that α7 nAChR agonist can provide neuroprotective effect on ICH-induced injury, independently of its anti-inflammatory actions.
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Exogenous delivery of the neurotrophin-3 (NT-3) gene may provide a potential therapeutic strategy for ischemic stroke. To investigate the neuroprotective effects of NT-3 expression controlled by 5HRE after focal cerebral ischemia, we constructed a recombinant retrovirus vector (RV) with five copies of hypoxia-responsive elements (5HRE or 5H) and NT-3 and delivered it to the rat brain. Three groups of rats received RV-5H-NT3, RV-5H-EGFP or saline injection. ⋯ Furthermore, the neurological status of RV-5H-NT3-transduced rats was better than that of RV-5H-EGFP- or saline-transduced animals from 1day to 4weeks after tMCAO. Our results demonstrated that 5HRE could modulate NT-3 expression in the ischemic brain environment and that the up-regulated NT-3 could effectively improve neurological status following tMCAO due to decreased initial damage. To avoid unexpected side effects, 5HRE-controlled gene expression might be a useful tool for gene therapy of ischemic disorders in the central nervous system.
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N-methyl-D-aspartate receptors (NMDARs) are glutamatergic by virtue of glutamate-binding GluN2 subunits and glycinergic by virtue of glycine-binding GluN1 and GluN3 subunits. The existence, location, and functional-significance of NMDARs containing both GluN2 and GluN3 subunits have as yet remained unelucidated. ⋯ Pharmacology revealed a triheteromeric-receptor with features common to glutamate-activated GluN1/GluN2-containing and glycine-activated GluN1/GluN3-containing diheteromeric NMDARs. However, unlike GluN1/GluN3 receptors, NMDARs at L1 inputs were activated by glutamate and blocked by d-AP5, Ca(2+)-permeable, and more efficient at integrating and potentiating EPSPs selectively over Str inputs during high-frequency stimulation while obviating the need for AMPAR-mediated depolarization.
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It has been proposed that the underlying epileptic process is mediated by changes in both excitatory and inhibitory circuits leading to the formation of hyper-excitable seizure networks. In this review we aim to shed light on the many physiological factors that modulate excitability within these networks. These factors have been discussed extensively in many reviews each as a separate entity and cannot be extensively covered in a single manuscript. ⋯ We present reported evidence supporting the existence of the epileptic brain in several states; interictal, peri-ictal and ictal, each with distinct excitability features. We then provide an overview of how many physiological factors influence the excitatory/inhibitory balance within the interictal state, where the networks are presumed to be functioning normally. We conclude that these changes result in constantly changing states of cortical excitability in patients with epilepsy.