Experimental neurology
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Experimental neurology · Nov 2001
X-irradiation of the contusion site improves locomotor and histological outcomes in spinal cord-injured rats.
We have determined whether X-irradiation of the injury site can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight drop device. Localized X-irradiation (20 Gy) of the injury site was performed at 20 min and 1, 2, 4, 7, and 17 days postinjury. ⋯ The extent of recovery was directly related to measurements of sparing of spinal cord tissue at the contusion center. Because the treatment time window occurred earlier in contusion than reported for transection injury, the results suggest that contusion injury rapidly initiates underlying radiation-sensitive processes that occur only following a delay of several weeks after transection injury. Further optimization of X-ray treatment may lead to a useful therapeutic modality for use in spinal cord contusion injury.
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Experimental neurology · Nov 2001
Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy.
Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. ⋯ In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.
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Experimental neurology · Nov 2001
The immunophilin ligand FK506 attenuates the axonal damage associated with rapid rewarming following posttraumatic hypothermia.
Our laboratory has shown that traumatically induced axonal injury (TAI) is significantly reduced by posttraumatic hypothermia followed by slow rewarming. Further, TAI can be exacerbated by rapid rewarming, and the damaging consequences of rapid rewarming can be reversed by cyclosporin A, which is believed to protect via blunting mitochondrial permeability transition (MPT). In this communication, we continue investigating the damaging consequences of rapid posthypothermic rewarming and the protective role of immunophilin ligands using another member of the immunophilin family, FK506, which does not affect MPT but rather inhibits calcineurin. ⋯ Combined labeling, using one chromagen to visualize both axonal changes, suggested that these two immunoreactive profiles revealed two distinct pathologies not occurring along the same axon. Collectively, these studies confirmed previous observations identifying the adverse consequences of rapid rewarming while also showing the complexity of the pathobiology of TAI. Additionally, the demonstration that FK506 is protective suggests that calcineurin may be a major target for neuroprotection.
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Experimental neurology · Nov 2001
Subchronic dermal application of N,N-diethyl m-toluamide (DEET) and permethrin to adult rats, alone or in combination, causes diffuse neuronal cell death and cytoskeletal abnormalities in the cerebral cortex and the hippocampus, and Purkinje neuron loss in the cerebellum.
N,N-Diethyl m-toluamide (DEET) and permethrin have been implicated as potential neurotoxic agents that may have played an important role in the development of illnesses in some veterans of the Persian Gulf War. To determine the effect of subchronic dermal application of these chemicals on the adult brain, we evaluated histopathological alterations in the brain of adult male rats following a daily dermal dose of DEET (40 mg/kg in 70% ethanol) or permethrin (0.13 mg/kg in 70% ethanol) or a combination of the two for 60 days. Control rats received a daily dermal dose of 70% ethanol for 60 days. ⋯ Analysis of glial fibrillary acidic protein immunoreactivity revealed significant hypertrophy of astrocytes in the hippocampus and the cerebellum of all treated groups (24-106% increase). Thus, subchronic dermal application of DEET and permethrin to adult rats, alone or in combination, leads to a diffuse neuronal cell death in the cerebral cortex, the hippocampal formation, and the cerebellum. Collectively, the above alterations can lead to many physiological, pharmacological, and behavioral abnormalities, particularly motor deficits and learning and memory dysfunction.
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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.