The Experts below are selected from a list of 127602 Experts worldwide ranked by ideXlab platform
Arthur W. English - One of the best experts on this subject based on the ideXlab platform.
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chondroitinase abc reduces time to muscle reinnervation and improves Functional Recovery after sciatic nerve transection in rats
Journal of Neurophysiology, 2012Co-Authors: Jennifer Nicolini, Manning J. Sabatier, Samuel J Rose, Arthur W. EnglishAbstract:Application of chondroitinase ABC (ChABC) to injured peripheral nerves improves axon regeneration, but it is not known whether Functional Recovery is also improved. Recordings of EMG activity [sole...
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Misdirection of Regenerating Axons and Functional Recovery Following Sciatic Nerve Injury in Rats
The Journal of Comparative Neurology, 2011Co-Authors: Shirley K. Hamilton, Marcus L. Hinkle, Jennifer Nicolini, Lindsay N. Rambo, April M. Rexwinkle, Sam J. Rose, Manning J. Sabatier, Deborah Backus, Arthur W. EnglishAbstract:Poor Functional Recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate Functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional Recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, Functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional Recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery.
Kazuya Kitamura - One of the best experts on this subject based on the ideXlab platform.
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human hepatocyte growth factor promotes Functional Recovery in primates after spinal cord injury
PLOS ONE, 2011Co-Authors: Kazuya Kitamura, Junichi Yamane, Kanehiro Fujiyoshi, Hiroshi Funakoshi, Fumika Toyota, Keigo Hikishima, Tatsuji Nomura, Toshikazu Nakamura, Masashi AokiAbstract:Many therapeutic interventions for spinal cord injury (SCI) using neurotrophic factors have focused on reducing the area damaged by secondary, post-injury degeneration, to promote Functional Recovery. Hepatocyte growth factor (HGF), which is a potent mitogen for mature hepatocytes and a mediator of the inflammatory responses to tissue injury, was recently highlighted as a potent neurotrophic factor in the central nervous system. We previously reported that introducing exogenous HGF into the injured rodent spinal cord using a herpes simplex virus-1 vector significantly reduces the area of damaged tissue and promotes Functional Recovery. However, that study did not examine the therapeutic effects of administering HGF after injury, which is the most critical issue for clinical application. To translate this strategy to human treatment, we induced a contusive cervical SCI in the common marmoset, a primate, and then administered recombinant human HGF (rhHGF) intrathecally. Motor function was assessed using an original open field scoring system focusing on manual function, including reach-and-grasp performance and hand placement in walking. The intrathecal rhHGF preserved the corticospinal fibers and myelinated areas, thereby promoting Functional Recovery. In vivo magnetic resonance imaging showed significant preservation of the intact spinal cord parenchyma. rhHGF-treatment did not give rise to an abnormal outgrowth of calcitonin gene related peptide positive fibers compared to the control group, indicating that this treatment did not induce or exacerbate allodynia. This is the first study to report the efficacy of rhHGF for treating SCI in non-human primates. In addition, this is the first presentation of a novel scale for assessing neurological motor performance in non-human primates after contusive cervical SCI.
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roles of es cell derived gliogenic neural stem progenitor cells in Functional Recovery after spinal cord injury
PLOS ONE, 2009Co-Authors: Gentaro Kumagai, Yohei Okada, Junichi Yamane, Narihito Nagoshi, Kazuya Kitamura, Masahiko Mukaino, Osahiko Tsuji, Kanehiro FujiyoshiAbstract:Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote Functional Recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the Functional Recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor Functional Recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the Recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to Functional improvement after SCI.
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hepatocyte growth factor promotes endogenous repair and Functional Recovery after spinal cord injury
Journal of Neuroscience Research, 2007Co-Authors: Kazuya Kitamura, Junichi Yamane, Akio Iwanami, Masaya Nakamura, Kota Watanabe, Yoshinori Suzuki, Daisuke Miyazawa, Shinsuke Shibata, Hiroshi Funakoshi, Shinichi MiyatakeAbstract:Many therapeutic interventions using neurotrophic factors or pharmacological agents have focused on secondary degeneration after spinal cord injury (SCI) to reduce damaged areas and promote axonal regeneration and Functional Recovery. Hepatocyte growth factor (HGF), which was identified as a potent mitogen for mature hepatocytes and a mediator of inflammatory responses to tissue injury, has recently been highlighted as a potent neurotrophic and angiogenic factor in the central nervous system (CNS). In the present study, we revealed that the extent of endogenous HGF up-regulation was less than that of c-Met, an HGF receptor, during the acute phase of SCI and administered exogenous HGF into injured spinal cord using a replication-incompetent herpes simplex virous-1 (HSV-1) vector to determine whether HGF exerts beneficial effects and promotes Functional Recovery after SCI. This treatment resulted in the significant promotion of neuron and oligodendrocyte survival, angiogenesis, axonal regrowth, and Functional Recovery after SCI. These results suggest that HGF gene delivery to the injured spinal cord exerts multiple beneficial effects and enhances endogenous repair after SCI. This is the first study to demonstrate the efficacy of HGF for SCI.
K Dhital - One of the best experts on this subject based on the ideXlab platform.
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Functional Recovery after dantrolene supplementation of cold stored hearts using an ex vivo isolated working rat heart model
PLOS ONE, 2018Co-Authors: Jeanette Villanueva, Hong C Chew, K Dhital, M Hicks, A DoyleAbstract:The ryanodine receptor antagonist dantrolene inhibits calcium release from the sarcoplasmic reticulum and reduces cardiac ischaemia-reperfusion injury (IRI) in global warm ischaemia models however the cardioprotective potential of dantrolene under hypothermic conditions is unknown. This study addresses whether the addition of dantrolene during cardioplegia and hypothermic storage of the donor heart can improve Functional Recovery and reduce IRI. Using an ex vivo isolated working heart model, Wistar rat (3 month and 12 month) hearts were perfused to acquire baseline haemodynamic measurements of aortic flow, coronary flow, cardiac output, pulse pressure and heart rate. Hearts were arrested and stored in Celsior preservation solution supplemented with 0.2–40 μM dantrolene for 6 hours at 4°C, then reperfused (15 min Langendorff, 30 min working mode). In 3-month hearts, supplementation with 1 μM dantrolene significantly improved aortic flow and cardiac output compared to unsupplemented controls however lactate dehydrogenase (LDH) release and contraction bands were comparable. In contrast, 40 μM dantrolene-supplementation yielded poor cardiac Recovery, increased post-reperfusion LDH but reduced contraction bands. All 3-month hearts stored in dantrolene displayed significantly reduced cleaved-caspase 3 intensities compared to controls. Analysis of cardioprotective signalling pathways showed no changes in AMPKα however dantrolene increased STAT3 and ERK1/2 signaling in a manner unrelated to Functional Recovery and AKT activity was reduced in 1 μM dantrolene-stored hearts. In contrast to 3-month hearts, no significant improvements were observed in the Functional Recovery of 12-month hearts following prolonged storage in 1 μM dantrolene. Conclusions: Dantrolene supplementation at 1 μM during hypothermic heart preservation improved Functional Recovery of young, but not older (12 month) hearts. Although the molecular mechanisms responsible for dantrolene-mediated cardioprotection are unclear, our studies show no correlation between improved Functional Recovery and SAFE and RISK pathway activation.
Bruce G. Gold - One of the best experts on this subject based on the ideXlab platform.
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neuroimmunophilin ligands improve Functional Recovery and increase axonal growth after spinal cord hemisection in rats
Journal of Neurotrauma, 2005Co-Authors: Jan Voda, Takayuki Yamaji, Bruce G. GoldAbstract:We have previously shown that FK506 accelerates the rate of nerve regeneration in the peripheral nervous system (PNS) and increases regeneration of central nervous system (CNS) axons into a peripheral nerve graft. In the present study, we examined whether FK506 and a nonimmunosuppressive derivative (FK1706) improve Functional Recovery and long distance regeneration following a hemisection lesion of spinal cord at T10/T11. Rats were given daily subcutaneous injections of either FK506 (2 mg/kg/day), FK1706 (2 mg/kg/day), an equivalent volume of saline or 30% DMSO as vehicle, respectively. Functional Recovery was assessed using a modified Tarlov/Klinger scale, walking along progressively narrower wooden beams (7.7–1.7 cm widths), and analysis of footprints obtained during walking. Compared to both control groups, FK506 and FK1706-treated animals demonstrated significant Functional Recovery 4 days (beam walking), 2 weeks (footprints), and 4 weeks (Tarlov/Klinger scale). By 11 weeks, FK506-treated and FK1706-t...
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neuroimmunophilin ligands improve Functional Recovery and increase axonal growth after spinal cord hemisection in rats
Journal of Neurotrauma, 2005Co-Authors: Jan Voda, Takayuki Yamaji, Bruce G. GoldAbstract:We have previously shown that FK506 accelerates the rate of nerve regeneration in the peripheral nervous system (PNS) and increases regeneration of central nervous system (CNS) axons into a peripheral nerve graft. In the present study, we examined whether FK506 and a nonimmunosuppressive derivative (FK1706) improve Functional Recovery and long distance regeneration following a hemisection lesion of spinal cord at T10/T11. Rats were given daily subcutaneous injections of either FK506 (2 mg/kg/day), FK1706 (2 mg/kg/day), an equivalent volume of saline or 30% DMSO as vehicle, respectively. Functional Recovery was assessed using a modified Tarlov/Klinger scale, walking along progressively narrower wooden beams (7.7-1.7 cm widths), and analysis of footprints obtained during walking. Compared to both control groups, FK506 and FK1706-treated animals demonstrated significant Functional Recovery 4 days (beam walking), 2 weeks (footprints), and 4 weeks (Tarlov/Klinger scale). By 11 weeks, FK506-treated and FK1706-treated animals were able to walk, albeit poorly, along even the narrowest (1.7 cm) beam. At 11 weeks, the spinal cords were re-exposed and a small piece of gel foam-soaked Fluoro-Gold was placed on the injured side 2-cm caudal to the first injury. Five days later, the animals were perfused and tissues prepared for fluorescence microscopy. FK506-treated and FK1706-treated rats demonstrate a significantly greater number of retrogradely labeled neurons in the red nucleus. The results implicate a nonimmunosuppressant mechanism in FK506's action and suggest that FK506 or a nonimmunosuppressant derivative may be useful for treatment of spinal cord injuries.
Manning J. Sabatier - One of the best experts on this subject based on the ideXlab platform.
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chondroitinase abc reduces time to muscle reinnervation and improves Functional Recovery after sciatic nerve transection in rats
Journal of Neurophysiology, 2012Co-Authors: Jennifer Nicolini, Manning J. Sabatier, Samuel J Rose, Arthur W. EnglishAbstract:Application of chondroitinase ABC (ChABC) to injured peripheral nerves improves axon regeneration, but it is not known whether Functional Recovery is also improved. Recordings of EMG activity [sole...
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Misdirection of Regenerating Axons and Functional Recovery Following Sciatic Nerve Injury in Rats
The Journal of Comparative Neurology, 2011Co-Authors: Shirley K. Hamilton, Marcus L. Hinkle, Jennifer Nicolini, Lindsay N. Rambo, April M. Rexwinkle, Sam J. Rose, Manning J. Sabatier, Deborah Backus, Arthur W. EnglishAbstract:Poor Functional Recovery found after peripheral nerve injury has been attributed to the misdirection of regenerating axons to reinnervate Functionally inappropriate muscles. We applied brief electrical stimulation (ES) to the common fibular (CF) but not the tibial (Tib) nerve just prior to transection and repair of the entire rat sciatic nerve, to attempt to influence the misdirection of its regenerating axons. The specificity with which regenerating axons reinnervated appropriate targets was evaluated physiologically using compound muscle action potentials (M responses) evoked from stimulation of the two nerve branches above the injury site. Functional Recovery was assayed using the timing of electromyography (EMG) activity recorded from the tibialis anterior (TA) and soleus (Sol) muscles during treadmill locomotion and kinematic analysis of hindlimb locomotor movements. Selective ES of the CF nerve resulted in restored M-responses at earlier times than in unstimulated controls in both TA and Sol muscles. Stimulated CF axons reinnervated inappropriate targets to a greater extent than unstimulated Tib axons. During locomotion, Functional antagonist muscles, TA and Sol, were coactivated both in stimulated rats and in unstimulated but injured rats. Hindlimb kinematics in stimulated rats were comparable to untreated rats, but significantly different from intact controls. Selective ES promotes enhanced axon regeneration but does so with decreased fidelity of muscle reinnervation. Functional Recovery is neither improved nor degraded, suggesting that compensatory changes in the outputs of the spinal circuits driving locomotion may occur irrespective of the extent of misdirection of regenerating axons in the periphery.
