The Experts below are selected from a list of 51 Experts worldwide ranked by ideXlab platform
P M Richardson - One of the best experts on this subject based on the ideXlab platform.
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responses of the Nerve Cell Body to axotomy
Neurosurgery, 2009Co-Authors: P M Richardson, Tizong Miao, Dongsheng Wu, Y Zhang, Xuenong BoAbstract:OBJECTIVE: Peripheral Nerve injury causes retrograde changes in the damaged neurons, which are beneficial to axonal regeneration. Better understanding of the mechanisms of induction and mediation of these conditioning responses would help to design strategies to invoke stronger regenerative responses in neurons in situations when these responses are inadequate. METHODS: Relevant literature is reviewed. RESULTS: Experimental preparations that measure the influence of peripheral axotomy on regeneration in the central axons of primary sensory neurons are useful to examine mechanisms of conditioning neurons. Despite 4 decades of speculation, the nature of the damage signals from injured Nerves that initiate axonal signals to the Nerve Cell Body remains elusive. Members of the family of neuropoietic cytokines are clearly implicated, but what induces them is unknown. Multiple changes in gene regulation in axotomized neurons have been described, and dozens of growth-associated genes have been identified: neurotrophic factors, transcription factors, molecules participating in axonal transport, and molecules active in the growth cone. The mechanisms of interaction of a few regeneration-associated molecules with the signaling cascades that lead to actin and tubulin remodeling at the growth cone are understood in some detail. In animals, viral gene therapy to deliver regeneration-associated genes to neurons or other local measures to induce these genes can improve regeneration. A few pharmacological agents, administered systemically, have small beneficial effects on axonal regeneration. CONCLUSION: Advances in laboratory research have provided knowledge of Cell Body responses to axotomy with clinical relevance.
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inflammation near the Nerve Cell Body enhances axonal regeneration
The Journal of Neuroscience, 1991Co-Authors: Xin Lu, P M RichardsonAbstract:Although crushed axons in a dorsal spinal root normally regenerate more slowly than peripheral axons, their regeneration can be accelerated by a conditioning lesion to the corresponding peripheral Nerve. These and other observations indicate that injury to peripheral sensory axons triggers changes in their Nerve Cell bodies that contribute to axonal regeneration. To investigate mechanisms of activating Nerve Cell bodies, an inflammatory reaction was provoked in rat dorsal root ganglia (DRG) through injection of Corynebacterium parvum. This inflammation enhanced regeneration in the associated dorsal root, increasing 4-fold the number of regenerating fibers 17 d after crushing; peripheral Nerve regeneration was not accelerated. A milder stimulation of dorsal root regeneration was detected after direct injection of isogenous macrophages into the ganglion. It is concluded that changes favorable to axonal regeneration can be induced by products of inflammatory Cells acting in the vicinity of the Nerve Cell Body. Satellite glial Cells and other unidentified Cells in lumbar DRG were shown by thymidine radioautography to proliferate after sciatic Nerve transection or injection of C. parvum into the ganglia. Intrathecal infusion of mitomycin C suppressed axotomy-induced mitosis of satellite glial Cells but did not impede axonal regeneration in the dorsal root or the peripheral Nerve. Nevertheless, the similarity in reactions of satellite glial Cells during 2 processes that activate neurons adds indirect support to the idea that non-neuronal Cells in the DRG might influence regenerative responses of primary sensory neurons.
Irvine G Mcquarrie - One of the best experts on this subject based on the ideXlab platform.
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calcium calmodulin dependent protein kinase iiα in optic axons moves with slow axonal transport and undergoes posttranslational modification
Biochemical and Biophysical Research Communications, 2001Co-Authors: Linda M Lund, Irvine G McquarrieAbstract:Abstract In neurons, the mRNA for calcium/calmodulin-dependent protein kinase II α (CKIIα) is known to be targeted to dendrites—where the enzyme is synthesized and supports postsynaptic functions. We are interested in knowing how neuronal proteins enter axons from the Nerve Cell Body, and the mechanism for protein transport to terminals. Because CKIIα immunofluorescence can be demonstrated in over 80% of retinal ganglion Cells, we asked whether this regulatory protein is being transported into optic axons. Using Sprague–Dawley rats, [35S] methionine was injected into the vitreous humor of the eye. Four days later, the optic Nerves, tracts, lateral geniculate ganglia, and superior colliculi were removed and processed for 2D-PAGE and Western blotting. Radiolabeled CKIIα appears to move with slow component b (SCb) of axonal transport, as is the case in rodent sciatic motor neurons. In addition, the radiolabeled CKIIα isoform that enters the optic Nerve is found to be 4 kDa heavier (in SDS–PAGE molecular mass) than the isoform in the optic tract, superior colliculus, and lateral geniculate nucleus. This reduction is likely the result of dephosphorylation, which is a mechanism used to regulate the enzyme's activity.
Xuenong Bo - One of the best experts on this subject based on the ideXlab platform.
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responses of the Nerve Cell Body to axotomy
Neurosurgery, 2009Co-Authors: P M Richardson, Tizong Miao, Dongsheng Wu, Y Zhang, Xuenong BoAbstract:OBJECTIVE: Peripheral Nerve injury causes retrograde changes in the damaged neurons, which are beneficial to axonal regeneration. Better understanding of the mechanisms of induction and mediation of these conditioning responses would help to design strategies to invoke stronger regenerative responses in neurons in situations when these responses are inadequate. METHODS: Relevant literature is reviewed. RESULTS: Experimental preparations that measure the influence of peripheral axotomy on regeneration in the central axons of primary sensory neurons are useful to examine mechanisms of conditioning neurons. Despite 4 decades of speculation, the nature of the damage signals from injured Nerves that initiate axonal signals to the Nerve Cell Body remains elusive. Members of the family of neuropoietic cytokines are clearly implicated, but what induces them is unknown. Multiple changes in gene regulation in axotomized neurons have been described, and dozens of growth-associated genes have been identified: neurotrophic factors, transcription factors, molecules participating in axonal transport, and molecules active in the growth cone. The mechanisms of interaction of a few regeneration-associated molecules with the signaling cascades that lead to actin and tubulin remodeling at the growth cone are understood in some detail. In animals, viral gene therapy to deliver regeneration-associated genes to neurons or other local measures to induce these genes can improve regeneration. A few pharmacological agents, administered systemically, have small beneficial effects on axonal regeneration. CONCLUSION: Advances in laboratory research have provided knowledge of Cell Body responses to axotomy with clinical relevance.
Kathryn J Jones - One of the best experts on this subject based on the ideXlab platform.
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gonadal steroid attenuation of developing hamster facial motoneuron loss by axotomy equal efficacy of testosterone dihydrotestosterone and 17 β estradiol
The Journal of Neuroscience, 2005Co-Authors: Christopher B Huppenbauer, Lisa Tanzer, Lydia L Doncarlos, Kathryn J JonesAbstract:In the hamster facial Nerve injury paradigm, we have established that androgens enhance both functional recovery from facial Nerve paralysis and the rate of regeneration in the adult, through intrinsic effects on the Nerve Cell Body response to injury and via an androgen receptor (AR)-mediated mechanism. Whether these therapeutic effects of gonadal steroids encompass neuroprotection from axotomy-induced Cell death is the focus of the present study. Virtually 100% of adult hamster facial motoneurons (FMNs) survive axotomy at the stylomastoid foramen (SMF), whereas, before postnatal day 15 (P15), developing FMNs undergo substantial axotomy-induced Cell death. The first part of the present study focuses on determining when ARs are first expressed in developing hamster FMNs. Using AR immunocytochemistry, it was found that males express ARs by P2 and females by P4, which is the earliest demonstration of AR expression in mammalian motoneurons reported thus far in the literature. The second half examines the neuroprotective effects of testosterone propionate, 17-β estradiol, and dihydrotestosterone on FMNs of P7 hamsters after facial Nerve transection at the SMF. The results demonstrate that androgens and estrogens are equally able to rescue ∼20% of FMNs from axotomy-induced Cell death, with the effects permanent. This study is the first to investigate the effects of both androgens and estrogens on axotomy-induced Cell death in one system and, with our previously published work, to validate the hamster FMN injury paradigm as a model of choice in the investigation of both neurotherapeutic and neuroprotective actions of gonadal steroids.
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testosterone enhancement of the Nerve Cell Body response to injury evidence using in situ hybridization and ribosomal dna probes
The Journal of Neuroscience, 1993Co-Authors: Nancy B Kinderman, Kathryn J JonesAbstract:In axotomized peripheral motoneurons capable of successful regeneration, one of the earliest morphological indicators of the injury response occurs within the nucleolus. In the initial part of this investigation, we mapped the nucleolar response of injured adult hamster facial motoneurons from a molecular perspective, utilizing in situ hybridization and ribosomal DNA probes complementary to stable rRNA. Recently, we have discovered that the gonadal steroid, testosterone propionate (TP), accelerates recovery from facial paralysis in the hamster by increasing the rate of regeneration of the fastest regrowing axons. In the second part of this study, the hypothesis that TP accomplishes these effects on facial Nerve regeneration through an enhancement of the Nerve Cell Body response to injury was tested using in situ hybridization and rDNA probes. Adult intact male hamsters were subjected to right facial Nerve axotomies at the stylomastoid foramen. One-half of the axotomized animals received subcutaneous implants of TP, with the remainder sham implanted. In situ hybridization with tritiated rDNA probes was accomplished and levels of hybridizable rRNA assessed both qualitatively and quantitatively. Axotomy alone induced an upregulation in rRNA levels, with peak changes occurring by 24 hr postoperative and continuing through postoperative day 4. These molecular changes in the nucleolar response preceded, by a full day, any morphological signs of the nucleolar reactive pattern previously found in this Cell type, and, as such, point to the usefulness of in situ hybridization as a tool to identify the earliest events associated with the axon reaction. A secondary smaller increase in rRNA levels was observed during the later stages of regeneration. TP significantly augmented the ribosomal response to injury, with levels of rRNA increased as early as 6 hr and the magnitude of the response greater than that occurring following axotomy alone. These results provide the first mechanistic step in the identification of the Cellular processes underlying gonadal steroid augmentation of neuronal reparative processes. We conclude that TP accelerates the “switch” from a normal to a reparative state and suggest that this priming effect may be causally related to the differential effects of TP on the regenerative properties of this Cell type.
Linda M Lund - One of the best experts on this subject based on the ideXlab platform.
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calcium calmodulin dependent protein kinase iiα in optic axons moves with slow axonal transport and undergoes posttranslational modification
Biochemical and Biophysical Research Communications, 2001Co-Authors: Linda M Lund, Irvine G McquarrieAbstract:Abstract In neurons, the mRNA for calcium/calmodulin-dependent protein kinase II α (CKIIα) is known to be targeted to dendrites—where the enzyme is synthesized and supports postsynaptic functions. We are interested in knowing how neuronal proteins enter axons from the Nerve Cell Body, and the mechanism for protein transport to terminals. Because CKIIα immunofluorescence can be demonstrated in over 80% of retinal ganglion Cells, we asked whether this regulatory protein is being transported into optic axons. Using Sprague–Dawley rats, [35S] methionine was injected into the vitreous humor of the eye. Four days later, the optic Nerves, tracts, lateral geniculate ganglia, and superior colliculi were removed and processed for 2D-PAGE and Western blotting. Radiolabeled CKIIα appears to move with slow component b (SCb) of axonal transport, as is the case in rodent sciatic motor neurons. In addition, the radiolabeled CKIIα isoform that enters the optic Nerve is found to be 4 kDa heavier (in SDS–PAGE molecular mass) than the isoform in the optic tract, superior colliculus, and lateral geniculate nucleus. This reduction is likely the result of dephosphorylation, which is a mechanism used to regulate the enzyme's activity.