Experimental neurology
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Experimental neurology · Sep 2005
Comparative Study Clinical TrialInhibition of neutral endopeptidase (NEP) facilitates neurogenic inflammation.
Neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) are involved in neuropeptide degradation and may modulate neurogenic inflammation. We therefore explored the effect of specific blockers of NEP and ACE on the intensity of neurogenic inflammation. We investigated eight subjects on three occasions. ⋯ No effect on the areas of hyperalgesia and allodynia could be detected. Our findings suggest that NEP but not ACE is most important for CGRP degradation in human skin. This may be of particular importance for the understanding of pain disorders like migraine or complex regional pain syndrome.
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Experimental neurology · Sep 2005
Comparative StudyUpregulation of Group I metabotropic glutamate receptors in neurons and astrocytes in the dorsal horn following spinal cord injury.
Of the glutamate receptor types, the metabotropic glutamate receptors (mGluRs) are G proteins coupled and can initiate a number of intracellular pathways leading to hyperexcitability of spinal neurons. In this study, we tested the expression of mGluRs to determine which cell types might contribute to sustained neuronal hyperexcitability in the lumbar enlargement with postoperative day (POD) 7 (early), 14 (late), and 30 (chronic phase) following spinal cord injury (SCI) by unilateral hemisection at T13 in Sprague-Dawley rats. Expression was determined by confocal analyses of immunocytochemical reaction product of neurons (NeuN positive) and astrocytes (GFAP positive) in the dorsal horn on both sides of the L4 segment. ⋯ In addition, mGluR(1) and mGluR(5) expression after hemisection was significantly increased in astrocytes in early, late, and chronic phases; whereas mGluR(2/3) did not display any significant changes. In conclusion, our data demonstrate long-term changes in expression levels of Group I mGluRs (mGluR(1) and mGluR(5)) in both neurons and astrocytes in segments below a unilateral SCI. Thus, permanent alterations in dorsal horn receptor expression may play important roles in transmission of nociceptive responses in the spinal cord following SCI.
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Experimental neurology · Sep 2005
Comparative StudyInduction of interleukin-6 in dorsal root ganglion neurons after gradual elongation of rat sciatic nerve.
In the reconstruction of a segmental defect in injured peripheral nerves, gradual nerve elongation has become an important alternative to nerve grafting. To clarify biochemical responses in peripheral sensory neurons after nerve elongation, we examined the expression of cytokines and neurotrophins related to nerve regeneration. We first established rat elongation models by lengthening left femurs up to 20.0 mm at the rate of 1.0, 2.0, or 20.0 mm/day. ⋯ In histochemical analysis, IL-6-immunoreactivity was predominant in neurofilament-positive, medium to large DRG neurons. Application of IL-6 to cultured Schwann cells increased mRNA for peripheral myelin protein 22 (PMP22), a major myelin component. These results suggest that IL-6 plays a key role in biochemical responses in peripheral sensory neurons after gradual nerve elongation.
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Experimental neurology · Aug 2005
Comparative StudyComparison of effects of methylprednisolone and anti-CD11d antibody treatments on autonomic dysreflexia after spinal cord injury.
Autonomic dysreflexia is a condition of episodic hypertension that develops after spinal cord injury (SCI). We previously showed that a two-day anti-inflammatory treatment with an anti-CD11d integrin monoclonal antibody (mAb), soon after SCI in rats, reduced the magnitude of dysreflexia for at least 6 weeks. Effects of methylprednisolone (MP), a commonly used neuroprotective treatment for SCI, on dysreflexia have never been examined. ⋯ However, both treatments led to increased fibre areas in the T9 segment, correlated with greater tissue integrity and smaller lesions, delineated by inflammatory cells. In summary, MP only temporarily decreases autonomic dysreflexia after SCI. The early beneficial effects of both treatments on dysreflexia do not relate to changes in the CGRP-immunoreactive afferent arbour but may correlate with decreased lesion progression.
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Axonal regeneration can be influenced by a conditioning lesion (an axonal injury made prior to a second test lesion). Previously, sympathetic neurons in vivo were shown to respond to a conditioning lesion with decreased neurite outgrowth, in contrast to the enhanced outgrowth observed in all other peripheral neurons examined. The present experiments tested the effects of a conditioning lesion on neurite outgrowth in vitro from the superior cervical ganglion (SCG) and the impact of several factors on that response. ⋯ Deletion of the gene for leukemia inhibitory factor (LIF), a gene induced by axotomy, did not abolish the conditioning lesion effect in SCG explants or dissociated cell cultures. In conclusion, sympathetic neurons are capable of responding to a conditioning lesion with increased neurite outgrowth. The hypothesis that the neuronal cell body response to axotomy plays an important role in the conditioning lesion response is discussed.