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Injured Neurons (injured + neuron)
Selected AbstractsDynamic changes in glypican-1 expression in dorsal root ganglion neurons after peripheral and central axonal injuryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2004Stefan Bloechlinger Abstract Glypican-1, a glycosyl phosphatidyl inositol (GPI)-anchored heparan sulphate proteoglycan expressed in the developing and mature cells of the central nervous system, acts as a coreceptor for diverse ligands, including slit axonal guidance proteins, fibroblast growth factors and laminin. We have examined its expression in primary sensory dorsal root ganglion (DRG) neurons and spinal cord after axonal injury. In noninjured rats, glypican-1 mRNA and protein are constitutively expressed at low levels in lumbar DRGs. Sciatic nerve transection results in a two-fold increase in mRNA and protein expression. High glypican-1 expression persists until the injured axons reinnervate their peripheral targets, as in the case of a crushed nerve. Injury to the central axons of DRG neurons by either a dorsal column injury or a dorsal root transection also up-regulates glypican-1, a feature that differs from most DRG axonal injury-induced genes, whose regulation changes only after peripheral and not central axonal injury. After axonal injury, the cellular localization of glypican-1 changes from a nuclear pattern restricted to neurons in noninjured DRGs, to the cytoplasm and membrane of injured neurons, as well as neighbouring non-neuronal cells. Sciatic nerve transection also leads to an accumulation of glypican-1 in the proximal nerve segment of injured axons. Glypican-1 is coexpressed with robo 2 and its up-regulation after axonal injury may contribute to an altered sensitivity to axonal growth or guidance cues. [source] Local isoform-specific NOS inhibition: A promising approach to promote motor function recovery after nerve injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 9 2010Bernardo Moreno-López Abstract Physical injury to a nerve is the most frequent cause of acquired peripheral neuropathy, which is responsible for loss of motor, sensory and/or autonomic functions. Injured axons in the peripheral nervous system maintain the capacity to regenerate in adult mammals. However, after nerve transection, stumps of damaged nerves must be surgically joined to guide regenerating axons into the distal nerve stump. Even so, severe functional limitations persist after restorative surgery. Therefore, the identification of molecules that regulate degenerative and regenerative processes is indispensable in developing therapeutic tools to accelerate and improve functional recovery. Here, I consider the role of nitric oxide (NO) synthesized by the three major isoforms of NO synthases (NOS) in motor neuropathy. Neuronal NOS (nNOS) seems to be the primary source of NO that is detrimental to the survival of injured motoneurons. Endothelial NOS (eNOS) appears to be the major source of NO that interferes with axonal regrowth, at least soon after injury. Finally, NO derived from inducible NOS (iNOS) or nNOS is critical to the process of lipid breakdown for Wallerian degeneration and thereby benefits axonal regrowth. Specific inhibitors of these isoforms can be used to protect injured neurons from degeneration and promote axonal regeneration. A cautious proposal for the treatment of acquired motor neuropathy using therapeutic tools that locally interfere with eNOS/nNOS activities seems to merit consideration. © 2010 Wiley-Liss, Inc. [source] Fractalkine and fractalkine receptors in human neurons and glial cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2002Kozo Hatori Abstract Fractalkine has been identified as a novel chemokine that exhibits cell adhesion and chemoattractive properties in the central nervous system (CNS), and the fractalkine receptors, CX3CR1, are also expressed in the CNS. In the present study, the expression of fractalkine and fractalkine receptors was investigated in enriched populations of human CNS neurons, astrocytes, and microglia. In addition, the regulatory role played by protein kinase C (PKC) in fractalkine secretion in neurons was determined in A1 human hybrid neuronal cell line produced between a human cerebral neuron and a human neuroblastoma cell. Human neurons and astrocytes expressed fractalkine mRNA as determined by the revserse transcriptase-polymerase chain reaction (RT-PCR) analysis, while human microglia preparation did not express the fractalkine message. Human neurons and microglia expressed CX3CR1 mRNA, but astrocytes did not. These results suggest that fractalkine secreted by CNS neurons and astrocytes produce biological effects in neurons and microglia. Although phorbol ester did not change the expression of fractalkine mRNA level in A1 hybrid neurons, it did upregulate fractalkine secretion over unstimulated controls. This upregulation of fractalkine production was suppressed by the treatment with Ro32-0432, a PKC inhibitor. These results indicate that intracellular signals transduced by PKC play an important role in the regulation of soluble fractalkine at the post-transcriptional level in human neurons. As for the biological function of fractalkine, extracellularly applied fractalkine increased the number of bromodeoxyuridine-labeled microglia 3-fold over the untreated controls, indicating fractalkine induces proliferation of human microglia. These observations suggest that fractalkine released by injured neurons could induce proliferation, activation and/or migration of microglia at the injured brain sites. © 2002 Wiley-Liss, Inc. [source] Painful neuropathy alters the effect of gabapentin on sensory neuron excitability in ratsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2004A. Kanai Background:, Pain following peripheral nerve injury is associated with increased excitability of sensory neurons. Gabapentin (GBP), a novel anticonvulsant with an uncertain mechanism of action, is an effective treatment for neuropathic pain. We therefore investigated the effect of GBP on dorsal root ganglion (DRG) neurons from normal rats and those with painful peripheral nerve injury. Methods:, Dorsal root ganglions were excised from rats with neuropathic pain behaviour following chronic constriction injury (CCI) of the sciatic nerve, and from normal rats. Intercellular recordings were made from myelinated sensory neuron somata using a microelectrode technique from DRGs bathed in artificial CSF with or without GBP (100 µM). Results:, Compared with normal neurons, injury decreased the refractory interval (RI) for repeat action potential (AP) generation increased the number of APs during sustained depolariza- tion, and shortened the after hyperpolarization following an AP. In normal neurons, GBP decreased the RI and increased the AP number during sustained depolarization. In an opposite fashion, the result of GBP application to injured neurons was a decreased number of APs during depolarization and no change in RI. In injured neurons only, GBP increased the time-to-peak for AP depolarization. Conclusions:, Nerve injury by CCI is associated with increased sensory neuron excitability, associated with a decreased AHP. In normal peripheral sensory neurons, GBP has pro-excitatory effects, whereas GBP decreases excitability in injured neurons, possibly on the basis of altered sodium channel function. [source] Ribosomal RNA transcriptional activation and processing in hamster rubrospinal motoneurons: Effects of axotomy and testosterone treatmentTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 4 2003Paul D. Storer Abstract Rubrospinal motoneurons (RSMN) represent a population of androgen receptor-expressing central motoneurons with limited regenerative potential relative to their peripheral counterparts. A key determinant of regenerative capability lies in the nucleolar reaction of injured neurons. To date, characterization of the nucleolar reaction in injured central motoneurons has not been accomplished. Furthermore, it has been documented that testosterone propionate (TP) augments peripheral motoneuron regeneration through regulation of the nucleolar reaction to injury. In this study, the effects of injury alone, or in conjunction with TP, on the nucleolar response of injured RSMN were examined using in situ hybridization (ISH) techniques. Castrated adult male hamsters were subjected to right spinal cord hemisection at the C7/T1 vertebral level. Half the animals were subcutaneously implanted with one Silastic TP capsule, with the other half sham implanted. ISH for precursor 45S and mature 28S rRNA was accomplished with a 3H-labeled ribosomal DNA probe specific to the external transcribed spacer region or to the 28S region of the ribosomal gene, respectively. Postoperative times of 2, 6, and 24 hours were selected for examination of precursor 45S rRNA (i.e., rRNA transcriptional activation) levels and 0.25, 2, 4, and 14 days for examination of mature rRNA (i.e., ribosome) levels. Transcriptional activation of the rRNA gene was rapidly and transiently increased in injured RSMN, analogously to previously documented effects of injury on rRNA transcription in peripheral motoneurons, but, in contrast, this did not translate into an increase in mature ribosomes. TP administration failed to affect positively the nucleolar response of injured RSMN at all. From this study, a key component underlying inherent differences in the regenerative capacity of peripheral vs. central motoneurons has been identified, which can be targeted in future experiments designed to enhance the regenerative potential of selective neuronal populations. J. Comp. Neurol. 458:326,333, 2003. © 2003 Wiley-Liss, Inc. [source] Aberrant Control of Motoneuronal Excitability in Amyotrophic Lateral Sclerosis: Excitatory Glutamate,/,D -Serine vs.CHEMISTRY & BIODIVERSITY, Issue 6 2010-Aminobutanoic Acid (GABA), Inhibitory Glycine/ Abstract The mechanism underlying selective motoneuronal loss in amyotrophic lateral sclerosis (ALS) remains uncertain. The pathogenesis appears to be a complex and multifactorial process. Glutamate excitotoxicity to motoneuron is one of the most intensely investigated targets for the treatment of ALS, and excessive motoneuronal excitation by glutamate through ionotropic glutamate receptors has been mainly demonstrated. However, development of clinically effective drug targeting glutamate is sometimes difficult, because some aspects of glutamergic signals also could be beneficial, as the injured neurons attempt to recruit endogenous recovery. This review is focused on identifying other mechanisms of imbalanced excitation in ALS motoneurons including excitation-modulating D -serine and inhibitory glycine/GABA. Further, validation of these mechanisms might ultimately lead us to new therapeutic targets for ALS. [source] | ||||||||||