Experimental neurology
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Experimental neurology · Nov 2001
Blocking NMDA receptors in the hippocampal dentate gyrus with AP5 produces analgesia in the formalin pain test.
The hippocampus is an integral component of the "limbic" system and, as such, may contribute to the negative affect and avoidance motivation experienced during pain. A substantial body of evidence indicates that the hippocampus processes pain-related information, that some hippocampal neurons respond exclusively to painful stimulation, and that long-term anatomical changes occur in dentate gyrus neurons, following noxious physical stimulation. NMDA receptor antagonist drugs administered to the hippocampus interfere with long-term potentiation, learning, and memory; these same drugs, when applied to the spinal cord, prevent the long-term neurophysiological changes caused by noxious physical stimulation. ⋯ The competitive NMDA receptor antagonist AP5 was injected into the dentate gyrus of alert, unrestrained rats either 5 min before or 15 min following the administration of a subcutaneous injection of formalin irritant. Pain behaviors in both acute and tonic phases of the formalin test were significantly reduced by AP5 treatments. These results support the hypothesis that the hippocampal formation is involved in pain-related neural processing and that NMDA receptor-sensitive mechanisms in the hippocampus are involved in pain perception and/or the expression of pain-related behaviors.
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Experimental neurology · Oct 2001
ReviewRegulation of the abundance of renal sodium transporters and channels by vasopressin.
Vasopressin plays a role in both salt and water balance in the kidney. Classic studies, utilizing isolated perfused tubules, have revealed that vasopressin increases sodium reabsorption in the kidney thick ascending limb and the collecting duct. Furthermore, the activity of several sodium transport proteins expressed in these segments, such as the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) and the epithelial sodium channel (ENaC), have been shown to be directly increased by vasopressin. ⋯ The alpha-subunit of Na-K-ATPase was increased by water restriction, but not by dDAVP infusion, and alpha-ENaC and the thiazide-sensitive cotransporter (NCC) were increased by dDAVP infusion but not by water restriction. Acute (60-min) in vivo exposure to dDAVP led to an increase in both beta- and gamma-ENaC abundance in kidney cortex homogenates, displaying the rapid nature of some of these changes. Overall these increases in sodium transporter and channel abundances likely contribute to both the antidiuretic and antinatriuretic actions of vasopressin.
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Experimental neurology · Oct 2001
Engraftment of serotonergic precursors enhances locomotor function and attenuates chronic central pain behavior following spinal hemisection injury in the rat.
Spinal cord injury (SCI) results in abnormal locomotor and pain syndromes in humans. T13 spinal hemisection in the rat results in development of permanent mechanical allodynia and thermal hyperalgesia partially due to interruption of descending inhibitory modulators such as serotonin (5-HT). We hypothesize that lumbar transplantation of nonmitotic cells that tonically secrete antinociceptive and trophic compounds will reduce the pain-like behavior and enhance locomotor recovery after SCI. ⋯ These effects were modulated by the 5-HT antagonist methysergide and reuptake inhibitor fluvoxamine. Bromodeoxyuridine and 5-HT immunoreactivity confirmed cell survival and graft location 4 weeks posttransplantation. These results support the therapeutic potential of bioengineered serotonin-secreting cell lines in reducing chronic central pain following spinal cord injury.
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Experimental neurology · Sep 2001
Audiogenic seizure susceptibility is induced by termination of continuous infusion of gamma-aminobutyric acid or an N-methyl-D-aspartic acid Antagonist into the inferior colliculus.
The inferior colliculus (IC) is strongly implicated in seizure initiation in a genetic form of audiogenic seizures (AGS) and in AGS observed during ethanol withdrawal (ETX). Ethanol is known to block the actions of excitatory amino acids (EAA) and enhance the actions of gamma-aminobutyric acid (GABA) in several brain areas, including the IC. The present study investigated the effects on susceptibility to AGS following withdrawal from continuous blockade of N-methyl-D-aspartic acid (NMDA) receptors or continuous activation of GABA receptors in the IC. ⋯ AGS susceptibility lasted for several hours and in 13% of animals persisted for up to 6 months. The current results support diminished GABAergic and elevated glutamatergic function in the IC as the critical mechanisms and sites for AGS initiation. The present study, coupled with previous evidence that chronic ethanol exposure reduced GABA-mediated inhibition and enhanced EAA-mediated excitation, suggests that these amino acid receptor-mediated alterations in the IC are key elements in initiating AGS during ethanol withdrawal.
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Experimental neurology · Sep 2001
Perforated microelectrode arrays implanted in the regenerating adult central nervous system.
Adult mammalian optic nerve axons are able to regenerate, when provided with the permissive environment of an autologous peripheral nerve graft, which is usually the sciatic nerve. This study demonstrates the ability of adult rat optic nerve axons to regenerate through the preformed perforations of a polyimide electrode carrier implanted at the interface between the proximal stump of the cut optic nerve and the stump of the peripheral nerve piece used for grafting. Evidence that retinal ganglion cells regenerated their axons through the perforated electrode carrier was obtained by retrograde labeling with a fluorescent dye deposited into the sciatic nerve graft beyond the nerve-carrier-nerve junction. ⋯ Third, electrical activity of the regenerating nerves was recorded after stimulating the retina with a flash of light. The results suggest that a regenerating central nerve tract may serve as an experimental model to implant artificial microdevices to monitor the physiological and topographical properties of neurites passing through the device or to stimulate them, thus interfering with their potential to grow. This study reports for the first time that the optic nerve has unique properties, which aids in the realization of these goals.