Experimental neurology
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Experimental neurology · Nov 1999
Cyclosporin A attenuates acute mitochondrial dysfunction following traumatic brain injury.
Experimental traumatic brain injury (TBI) results in a rapid and significant necrosis of cortical tissue at the site of injury. In the ensuring hours and days, secondary injury exacerbates the primary damage, resulting in significant neurological dysfunction. Recent reports from our lab and others have demonstrated that the immunosuppressant cyclosporin A (CsA) is neuroprotective following TBI. ⋯ Similarly, synaptosomes isolated from CsA-treated animals demonstrate a significant increase in mitochondria membrane potential, accompanied by lower levels of intramitochondrial Ca2+ and reactive oxygen species production than seen in vehicle-treated animals. These results suggest that the neuroprotective properties of CsA are mediated through modulation of the MPTP and maintenance of mitochondria homeostasis. Amelioration of cortical damage with CsA indicates that pharmacological therapies can be devised which will significantly alter neurological outcome after injury.
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Experimental neurology · Oct 1999
Neuroprotective effects of interleukin-10 following excitotoxic spinal cord injury.
Intraspinal injection of quisqualic acid (QUIS) produces excitotoxic injury with pathological characteristics similar to those associated with ischemic and traumatic spinal cord injury (SCI). Inflammatory responses appear to be a major component of the secondary neuronal injury initiated by SCI and play a role in the pathogenesis of QUIS-induced injury. IL-10 is a potent antiinflammatory cytokine that has been shown to reduce inflammation and improve functional outcome in human and animal models of inflammatory diseases. ⋯ When given systemically, IL-10 significantly decreased lesion volume by 18.1% in the more advanced injury (P < 0.05), but did not effect the more acute injury. These divergent effects were attributed to the modest inflammatory response in the short-term injury compared to the more robust inflammatory response in the more chronic injury. In conclusion, reducing the inflammatory response to SCI by systemic administration of IL-10 resulted in a significant reduction in neuronal damage, suggesting that targeting injury-induced inflammation may be an effective treatment strategy for acute SCI.
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Experimental neurology · Oct 1999
Increased calcitonin gene-related peptide immunoreactivity in gracile nucleus after partial sciatic nerve injury: age-dependent and originating from spared sensory neurons.
Following a unilateral chronic constriction injury of the sciatic nerve, calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fiber density increases in the ipsilateral gracile nucleus, and this is more pronounced in aged (16-month) rats where the fibers are dystrophic. In this study we show that a second type of partial sciatic nerve injury, a half-transection, also induces CGRP-IR fibers in the gracile nucleus, but this effect is strongly age-dependent, being much more pronounced in 8- to 10-month-old rats than in 2- to 3-month-old rats. Dystrophic CGRP-IR fibers were rarely observed in 8- to 10-month-old animals, so the increased reaction in aged animals and axonal dystrophy are separate phenomena. ⋯ Using combined fluorescent dye tracing with in situ hybridization for CGRP mRNA or CGRP immunostaining, we further showed that CGRP-expressing DRG neuron profiles with central projections to the gracile nucleus had peripheral axons spared by the partial nerve injury. We conclude that the increased CGRP immunoreactivity in the gracile nucleus following partial sciatic nerve injury originates from primary sensory neurons with axons spared by the injury. These neurons may still transmit cutaneous sensory information and thus the increased CGRP immunoreactive fibers in the gracile nucleus may be involved in the mechanical allodynia characteristic of neuropathic pain syndromes following partial nerve injury.
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Experimental neurology · Oct 1999
Effect of recombinant human nerve growth factor on cisplatin neurotoxicity in rats.
In this study we evaluated the effect of recombinant human nerve growth factor (rhNGF) on cisplatin (CDDP)-induced sensory neuronopathy in an experimental paradigm in the rat. Young adult female Wistar rats were treated with CDDP (2 mg/kg ip twice weekly for nine times) alone or in combination with rhNGF (1 mg/kg sc on alternate days). The effect of CDDP +/- NGF treatment was evaluated with behavioral (tail-flick test) and neurophysiological (nerve conduction velocity in the tail) methods immediately after treatment and after a follow-up period of 6 weeks. ⋯ However, for each of the parameters examined the neuroprotection obtained with rhNGF treatment was not complete. At the follow-up examination no differences between the three groups were observed in tail-flick test and nerve conduction velocity. We conclude that rhNGF, administered according to the schedule used in this experiment, exerts a biologically significant neuroprotective effect against CDDP peripheral neurotoxicity.
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Experimental neurology · Sep 1999
Clenbuterol, a beta(2)-adrenoceptor agonist, improves locomotor and histological outcomes after spinal cord contusion in rats.
An important goal of rehabilitation following spinal cord injury is recovery of locomotor function and muscular strength. In the present studies, we determined whether the beta(2)-agonist, clenbuterol, can improve recovery of locomotor function following spinal cord injury. A model of spinal cord injury was examined in which four graded levels of contusion injury were produced in rats at the level of T10 with a weight-drop device. ⋯ However, clenbuterol caused substantial enhancement of recovery of locomotor function at the two most severe levels of injury (BBB scores 10-12 vs 2-4). In addition, the extent of recovery was directly related to sparing of spinal cord tissue at the contusion center in both untreated and clenbuterol-treated spinal cords. Optimization of beta(2)-agonist treatment may lead to a useful therapeutic modality for treatment of spinal cord contusion injury.