Nerve Crush

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Jost B Jonas - One of the best experts on this subject based on the ideXlab platform.

  • neuroprotective effect of intravitreal cell based glucagon like peptide 1 production in the optic Nerve Crush model
    Acta Ophthalmologica, 2010
    Co-Authors: Rong Zhang, Haijuan Zhang, Jost B Jonas, Christine Wallrapp
    Abstract:

    . Purpose:  To examine the effect of intraocularly produced glucagon-like peptide-1 (GLP-1) on the survival rate of retinal ganglion cells in an optic Nerve Crush model. Methods:  Forty-one Sprague–Dawley rats were divided into a study group (21 animals) in which 4 beads with 3000 genetically modified cells to produce GLP-1 were intravitreally implanted into the right eye; a saline control group (n = 12) with intravitreal saline injection; and a GLP-1 negative bead control group (n = 8) in which 4 beads with 3000 cells without GLP-1 production were intravitreally implanted. The right optic Nerves of all animals were Crushed in a standardized manner. After labeling the retinal ganglion cells by injecting 3% fluorogold into the superior colliculus, the animals were sacrificed, and the ganglion cells were counted on retinal flat mounts. Results:  The retinal ganglion cell density of the right eyes was significantly higher in the study group (median: 2081 cells/mm2; range: 1182–2953 cells/mm2) than in the GLP-1 bead negative control group (median: 1328 cells/mm2; range: 1007–2068 cells/mm2; p = 0.002) and than in the saline control group (median: 1777 cells/mm2; range: 1000–2405 cells/mm2; p = 0.07). Correspondingly, the survival rate (ratio of retinal ganglion cell density of right eye/left eye) was significantly higher in the study group (median: 0.72; range: 0.40–1.04) than in the GLP-1 bead negative control group (median: 0.44; range: 0.36–0.68; p = 0.003) and than in the saline control group (median: 0.56; range: 0.36–0.89; p = 0.03). Conclusion:  Glucagon-like peptide-1 produced by intravitreally implanted cell beads was associated with a higher survival rate of retinal ganglion cells after an experimental optic Nerve Crush in rats.

  • effect of brimonidine on retinal ganglion cell survival in an optic Nerve Crush model
    American Journal of Ophthalmology, 2009
    Co-Authors: Liang Xu, Haijuan Zhang, Shixian Zhang, Mingliang Pu, Jost B Jonas
    Abstract:

    Purpose To investigate the effect of brimonidine on the retinal ganglion cell survival in an optic Nerve Crush model. Design Experimental animal study. Methods Twenty-four Sprague-Dawley rats were divided into a study group of eight animals receiving intraperitoneal injections of brimonidine (1 mg/kg) and into a control group of 12 animals receiving intraperitoneal saline injections. All injections were performed one hour before the optic Nerve crash and daily afterwards. For each animal, the right optic Nerve was Crushed for 60 seconds by a microclip with 40-g power. At 23 days after the optic Nerve Crush, the retinal ganglion cells were retrogradely labeled by injecting 3% fluorogold into both sides of the superior colliculus of the brain. At four weeks after the optic Nerve Crush, the animals were sacrificed. Photographs taken from retinal flat mounts were assessed for number and density of the retinal ganglion cells. Results The retinal ganglion cell density of the right eyes with an optic Nerve lesion was statistically significantly ( P = .02) higher in the brimonidine study group (1281 ± 189 cells/mm 2 ) than in the control group (1060 ± 148 cells/mm 2 ). Correspondingly, the survival rate (ratio of retinal ganglion cell density in the right eye divided by cell density in the left eye) was statistically significantly ( P = .027) higher in the study group than in the control group (61.0% ± 6.0% vs 53.5±8.0%). Conclusion Intraperitoneal injections of brimonidine given prophylactically prior to and posttreatment daily after an experimental and standardized optic Nerve Crush in rats were associated with a higher survival rate of retinal ganglion cells.

  • effect of brimonidine on retinal ganglion cell survival in an optic Nerve Crush model
    American Journal of Ophthalmology, 2009
    Co-Authors: Haijuan Zhang, Shixian Zhang, Jost B Jonas
    Abstract:

    Purpose To investigate the effect of brimonidine on the retinal ganglion cell survival in an optic Nerve Crush model. Design Experimental animal study. Methods Twenty-four Sprague-Dawley rats were divided into a study group of eight animals receiving intraperitoneal injections of brimonidine (1 mg/kg) and into a control group of 12 animals receiving intraperitoneal saline injections. All injections were performed one hour before the optic Nerve crash and daily afterwards. For each animal, the right optic Nerve was Crushed for 60 seconds by a microclip with 40-g power. At 23 days after the optic Nerve Crush, the retinal ganglion cells were retrogradely labeled by injecting 3% fluorogold into both sides of the superior colliculus of the brain. At four weeks after the optic Nerve Crush, the animals were sacrificed. Photographs taken from retinal flat mounts were assessed for number and density of the retinal ganglion cells. Results The retinal ganglion cell density of the right eyes with an optic Nerve lesion was statistically significantly ( P = .02) higher in the brimonidine study group (1281 ± 189 cells/mm 2 ) than in the control group (1060 ± 148 cells/mm 2 ). Correspondingly, the survival rate (ratio of retinal ganglion cell density in the right eye divided by cell density in the left eye) was statistically significantly ( P = .027) higher in the study group than in the control group (61.0% ± 6.0% vs 53.5±8.0%). Conclusion Intraperitoneal injections of brimonidine given prophylactically prior to and posttreatment daily after an experimental and standardized optic Nerve Crush in rats were associated with a higher survival rate of retinal ganglion cells.

Xiaorong Liu - One of the best experts on this subject based on the ideXlab platform.

  • correlation between retinal ganglion cell loss and Nerve Crush force impulse established with an instrumented tweezers in mice
    bioRxiv, 2019
    Co-Authors: Xiaorong Liu, Liang Feng, Ishan Shinde, James Cole, John B Troy, Laxman Saggere
    Abstract:

    Purpose: Rodent models of optic Nerve Crush have often been used to study degeneration and regeneration of retinal ganglion cells (RGCs) and their axons as well as the underlying molecular mechanisms. However, optic Nerve Crush results from different laboratories exhibit a diverse range of RGC damage lacking consistency, reliability and a means for quantification of the degree of axonal damage. Therefore, in this study, we examined the correlation between RGC axon loss and impulse, the product of force and duration, applied through self-closing Dumont tweezers to Crush optic Nerves. Methods: We instrumented a pair of standard self-closing #N7 tweezers with miniature foil strain gauges at optimal locations on both arms of the tweezers. The instrumented tweezers was capable of recording the tip closure forces in the form of voltages, which were calibrated through load cells to corresponding tip closure forces over the operating range. Using the instrumented tweezers, we Crushed the optic Nerves of multiple mice with varied forces and durations and the Crushed optic Nerves were dissected and prepared for immunostaining for axon counting. Results: We plotted surviving axon density versus the corresponding Crush force impulse. We found that the surviving axon density correlated with Crush force, with longer duration and stronger Crush forces producing consistently more axon damage. Conclusions: A simple and repeatable technique for measurement of optic Nerve Crush forces in real-time is introduced here for the first time. Using the instrumented tweezers presented in this study, experimenters can be trained to apply controlled forces during optic Nerve Crush to produce consistent and predictable post-Crush cell death. This should permit future studies a way to produce Nerve damage more reliably than is available now.

  • different functional susceptibilities of mouse retinal ganglion cell subtypes to optic Nerve Crush injury
    Experimental Eye Research, 2017
    Co-Authors: Zhen Puyang, Xiaorong Liu, John B Troy, Hai Qing Gong, Peiji Liang
    Abstract:

    Abstract In optic neuropathies, the progressive deterioration of retinal ganglion cell (RGC) function leads to irreversible vision loss. Increasing experimental evidence suggests differing susceptibility for RGC functional subtypes. Here with multi-electrode array recordings, RGC functional loss was characterized at multiple time points in a mouse model of optic Nerve Crush. Firing rate, latency of response and receptive field size were analyzed for ON, OFF and ON-OFF RGCs separately. It was observed that responses and receptive fields of OFF cells were impaired earlier than ON cells after the injury. For the ON-OFF cells, the OFF component of response was also more susceptible to optic Nerve injury than the ON component. Moreover, more ON transient cells survived than ON sustained cells post the Crush, implying a diversified vulnerability for ON cells. Together, these data support the contention that RGCs’ functional degeneration in optic Nerve injury is subtype dependent, a fact that needs to be considered when developing treatments of glaucomatous retinal ganglion cell degeneration and other optic neuropathies.

  • overexpression of brain derived neurotrophic factor protects large retinal ganglion cells after optic Nerve Crush in mice
    eNeuro, 2017
    Co-Authors: Liang Feng, John B Troy, Zhen Puyang, Hui Chen, Peiji Liang, Xiaorong Liu
    Abstract:

    Abstract Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic Nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic Nerve Crush by in vivo imaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein transgene that accounts for ∼11% of the total SMI-32–positive RGCs. The median survival time of this subgroup of SMI-32 cells was 1 week after Nerve injury in control mice but 2 weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was 2 weeks, suggesting that these large-soma RGCs are especially vulnerable to optic Nerve Crush injury. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF up-regulation extended axon survival. Together, our results demonstrate that the time course of RGC loss induced by optic Nerve injury is type specific and that overexpression of BDNF prolongs the survival of one subgroup of SMI-32–positive RGCs.

  • retinal ganglion cell loss is delayed following optic Nerve Crush in nlrp3 knockout mice
    Scientific Reports, 2016
    Co-Authors: Zhen Puyang, Xiaorong Liu, Liang Feng, John B Troy, Hui Chen, Peiji Liang
    Abstract:

    The NLRP3 inflammasome, a sensor for a variety of pathogen- and host-derived threats, consists of the adaptor ASC (Apoptosis-associated Speck-like protein containing a Caspase Activation and Recruitment Domain (CARD)), pro-caspase-1, and NLRP3 (NOD-Like Receptor family Pyrin domain containing 3). NLRP3-induced neuroinflammation is implicated in the pathogenesis and progression of eye diseases, but it remains unclear whether activation of NLRP3 inflammasome contributes to retinal ganglion cell (RGC) death. Here we examined NLRP3-induced neuroinflammation and RGC survival following partial optic Nerve Crush (pONC) injury. We showed that NLRP3 was up-regulated in retinal microglial cells following pONC, propagating from the injury site to the optic Nerve head and finally the entire retina within one day. Activation of NLRP3-ASC inflammasome led to the up-regulation of caspase-1 and a proinflammatory cytokine, interleukin-1β (IL-1β). In NLRP3 knockout mice, up-regulation of ASC, caspase-1, and IL-1β were all reduced, and, importantly, RGC and axon loss was substantially delayed following pONC injury. The average survival time of RGCs in NLRP3 knockout mice was about one week longer than for control animals. Taken together, our study demonstrated that ablating the NLRP3 gene significantly reduced neuroinflammation and delayed RGC loss after optic Nerve Crush injury.

Tom F. Lue - One of the best experts on this subject based on the ideXlab platform.

  • Neurturin enhances the recovery of erectile function following bilateral cavernous Nerve Crush injury in the rat.
    Journal of brachial plexus and peripheral nerve injury, 2007
    Co-Authors: Anthony J Bella, Thomas M. Fandel, Kavirach Tantiwongse, William O. Brant, Robert D Klein, Carlos A Garcia, Tom F. Lue
    Abstract:

    Background The molecular mechanisms responsible for the survival and preservation of function for adult parasympathetic ganglion neurons following injury remain incompletely understood. However, advances in the neurobiology of growth factors, neural development, and prevention of cell death have led to a surge of clinical interest for protective and regenerative neuromodulatory strategies, as surgical therapies for prostate, bladder, and colorectal cancers often result in neuronal axotomy and debilitating loss of sexual function or continence. In vitro studies have identified neurturin, a glial cell line-derived neurotrophic factor, as a neuromodulator for pelvic cholinergic neurons. We present the first in vivo report of the effects of neurturin upon the recovery of erectile function following bilateral cavernous Nerve Crush injury in the rat.

  • fk1706 enhances the recovery of erectile function following bilateral cavernous Nerve Crush injury in the rat
    The Journal of Sexual Medicine, 2007
    Co-Authors: Anthony J Bella, Narihiko Hayashi, Rafael Carrion, Raymond D Price, Tom F. Lue
    Abstract:

    ABSTRACT Introduction Advances in neurobiology have led to a surge of clinical interest in the development of protective and regenerative neuromodulatory strategies, as surgical therapies for prostate cancer often result in neuronal damage and debilitating loss of sexual function. Aim To investigate the dose-dependent efficacy of FK1706, a nonimmunosuppressant immunophilin ligand, for the recovery of erectile function following bilateral cavernous Nerve Crush injury in the rat. Main Outcome Measures Recovery of erectile function was assessed by cavernous Nerve electrostimulation and reported as maximal increase of intracavernous pressure (ICP) and area under the curve (AUC). Changes in animal weights, percentage completion of treatment course, and survival were compared between groups. Methods Thirty-five Sprague–Dawley male rats were randomly divided into five equal groups: seven animals received a sham operation, whereas 28 animals underwent bilateral cavernous Nerve Crush injury, followed by subcutaneous injection of vehicle alone (1.0 mL/kg), or low (0.1 mg/kg), medium (0.32 mg/kg), or high dose (1.0 mg/kg) FK1706 5 days per week for 8 weeks. Results Erectile dysfunction did not occur in the sham group (mean maximal ICP increase of 100.8 ± 6.3 cmH 2 O), whereas Nerve injury and vehicle treatment produced a significant reduction in ICP response to 34.4 ± 12.8 cmH 2 O. The mean ICP increase for high-dose FK106 treatment was 73.9 ± 6.3 cmH 2 O ( P 2 O and 56.9 ± 8.3 for low and medium doses ( P  > 0.05). Similar stepwise findings were observed using AUC data. No significant maximal aortic blood pressure or weight differences occurred between groups and all animals completed treatment. Conclusion High-dose subcutaneous FK1706 therapy promoted recovery of erectile function following bilateral cavernous Nerve Crush injury in the rat. No significant differences between groups were observed for changes in weight, and the 8-week treatment course was completed for all animals. Bella AJ, Hayashi N, Carrion RE, Price R, and Lue TF. FK1706 enhances the recovery of erectile function following bilateral cavernous Nerve Crush injury in the rat.

  • the effect of fk1706 on erectile function following bilateral cavernous Nerve Crush injury in a rat model
    The Journal of Urology, 2006
    Co-Authors: Narihiko Hayashi, Rafael Carrion, Raymond D Price, Thomas X Minor, Lora Nunes, Tom F. Lue
    Abstract:

    Purpose: We investigated the neurotrophic effect of FK1706 on erectile recovery following bilateral cavernous Nerve Crush injury in a rat model.Materials and Methods: A total of 28 male Sprague-Dawley rats were randomly divided into 4 equal groups. Seven animals underwent sham operation and subcutaneous vehicle injection, whereas 21 underwent bilateral cavernous Nerve Crush injury followed by vehicle injection alone, or by low (0.1 mg/kg) or high (1.0 mg/kg) dose FK1706 treatment. Injections were continued 5 days weekly for 8 weeks. Erectile function was then assessed by cavernous Nerve electrostimulation and penile tissue was evaluated immunohistochemically.Results: No erectile dysfunction was identified in the sham treated group (mean maximal intracavernous pressure ± SEM 106.8 ± 6.4 cm H2O), whereas Nerve injury significantly decreased ICP to 17.9 ± 7.0 cm H2O. FK1706 facilitated neural and erectile recovery in a concentration dependent manner with a mean ICP in the high dose FK treatment group of 80.1...

Paola Paggi - One of the best experts on this subject based on the ideXlab platform.

  • nicotinic acetylcholine receptor subtypes in the rat sympathetic ganglion pharmacological characterization subcellular distribution and effect of pre and postganglionic Nerve Crush
    Journal of Neuropathology and Experimental Neurology, 2004
    Co-Authors: Arianna Del Signore, M. Moretti, C. Gotti, Angela Rizzo, Paola Paggi
    Abstract:

    Nicotinic acetylcholine receptors (nAChRs) mediate fast synaptic transmission in autonomic ganglia, which innervate and control the activity of most visceral organs. By combining ultrastructural, immunocytochemical, and pharmacological analyses, we characterized the nAChR subtypes in the rat superior cervical ganglion (SCG) and the effect of pre- and postganglionic Nerve Crush on their number in the ganglion and their distribution at the intraganglionic synapses. Binding with radioactive nicotinic ligands, immunoprecipitation, and immunolocalization experiments revealed the presence of different nAChR subtypes: those containing the alpha3 subunit associated with beta4 and/or beta2 subunits that bind 3H-Epibatidine with high affinity, and those containing the alpha7 subunit that bind 125I-alphaBungarotoxin. After postganglionic Nerve Crush, the number of nicotinic receptors and immunopositive intraganglionic synapses for each nAChR subunit strongly decreased. Both the number of nAChRs and immunoreactivity recovered 26 days after injury, when regenerating postganglionic fibers had reinnervated the peripheral target organs, as shown by the restoration of tyrosine hydroxylase immunoreactivity in the iris. This observation and the lack of any effect of preganglionic Nerve Crush on the number of nicotinic receptors suggest that the peripheral targets affect the organization of intraganglionic synapses in adult SCG.

  • Ultrastructural alterations induced in quail ciliary neurons by postganglionic Nerve Crush and by Ricinus toxin administration, separately and in combination.
    Neuroscience, 1994
    Co-Authors: M. E. De Stefano, A. Ciofi Luzzatto, Enrico Mugnaini, Paola Paggi, Giovanni Toschi
    Abstract:

    Abstract The response to postganglionic Nerve Crush and Ricinus toxin administration by the ciliary neurons of the quail ciliary ganglion was investigated at the ultrastructural level. The toxin was either applied at the Crush site on the postganglionic Nerves or injected into the anterior eye chamber without any other operative intervention. Crush of postganglionic Nerves without toxin administration and saline injection into the anterior eye chamber served as controls for the two toxin administration procedures. Postganglionic Nerve Crush caused a distinct chromatolytic reaction, accompanied by massive detachment of the preganglionic axon terminals from the ciliary neurons and loss of most of the synapses, both chemical and electrical. This process does not induce cell death and is reversible. Saline injection in the anterior eye chamber caused a moderate retrograde reaction in some of the ciliary neurons, presumably as a consequence of paracentesis. The changes consisted mainly of an increase of perikaryal neurofilaments with, at most, a minor detachment of the preganglionic boutons from a small portion of the cell body at the nuclear pole. Ricinus toxin administration induced neuronal degeneration following a pattern common to both delivery modes. The degenerative process consisted of disruption and detachment of polyribosomes from the rough endoplasmic reticulum, an increase of smooth cisterns and tubules, a dramatic increase of neurofilament bundles, compartmentalization of the cytoplasmic organelles and, finally, karyorrhexis and cell lysis. The final stages of Ricinus toxin degeneration involve a progressive accumulation of extracellular flocculo-filamentous material and cell lysis. After administration of Ricinus toxin to the Crush site, ricin-affected neurons showed withdrawal of the preganglionic boutons from a portion of the ciliary neuron, especially at the nuclear pole. After Ricinus toxin injection into the anterior eye chamber, however, the bouton shell surrounding the affected ciliary neurons remained intact in the early stages of degeneration. Detachment of the preganglionic terminals and disruption of the cell junctions, therefore, is the consequence of Nerve Crush and not of the toxin itself. This study demonstrates that quail ciliary neurons are a suitable model for experimental neuropathology and neurotoxicology.

Zhen Puyang - One of the best experts on this subject based on the ideXlab platform.

  • different functional susceptibilities of mouse retinal ganglion cell subtypes to optic Nerve Crush injury
    Experimental Eye Research, 2017
    Co-Authors: Zhen Puyang, Xiaorong Liu, John B Troy, Hai Qing Gong, Peiji Liang
    Abstract:

    Abstract In optic neuropathies, the progressive deterioration of retinal ganglion cell (RGC) function leads to irreversible vision loss. Increasing experimental evidence suggests differing susceptibility for RGC functional subtypes. Here with multi-electrode array recordings, RGC functional loss was characterized at multiple time points in a mouse model of optic Nerve Crush. Firing rate, latency of response and receptive field size were analyzed for ON, OFF and ON-OFF RGCs separately. It was observed that responses and receptive fields of OFF cells were impaired earlier than ON cells after the injury. For the ON-OFF cells, the OFF component of response was also more susceptible to optic Nerve injury than the ON component. Moreover, more ON transient cells survived than ON sustained cells post the Crush, implying a diversified vulnerability for ON cells. Together, these data support the contention that RGCs’ functional degeneration in optic Nerve injury is subtype dependent, a fact that needs to be considered when developing treatments of glaucomatous retinal ganglion cell degeneration and other optic neuropathies.

  • overexpression of brain derived neurotrophic factor protects large retinal ganglion cells after optic Nerve Crush in mice
    eNeuro, 2017
    Co-Authors: Liang Feng, John B Troy, Zhen Puyang, Hui Chen, Peiji Liang, Xiaorong Liu
    Abstract:

    Abstract Brain-derived neurotrophic factor (BDNF), a neurotrophin essential for neuron survival and function, plays an important role in neuroprotection during neurodegenerative diseases. In this study, we examined whether a modest increase of retinal BDNF promotes retinal ganglion cell (RGC) survival after acute injury of the optic Nerve in mice. We adopted an inducible Cre-recombinase transgenic system to up-regulate BDNF in the mouse retina and then examined RGC survival after optic Nerve Crush by in vivo imaging. We focused on one subtype of RGC with large soma expressing yellow fluorescent protein transgene that accounts for ∼11% of the total SMI-32–positive RGCs. The median survival time of this subgroup of SMI-32 cells was 1 week after Nerve injury in control mice but 2 weeks when BDNF was up-regulated. Interestingly, we found that the survival time for RGCs taken as a whole was 2 weeks, suggesting that these large-soma RGCs are especially vulnerable to optic Nerve Crush injury. We also studied changes in axon number using confocal imaging, confirming first the progressive loss reported previously for wild-type mice and demonstrating that BDNF up-regulation extended axon survival. Together, our results demonstrate that the time course of RGC loss induced by optic Nerve injury is type specific and that overexpression of BDNF prolongs the survival of one subgroup of SMI-32–positive RGCs.

  • retinal ganglion cell loss is delayed following optic Nerve Crush in nlrp3 knockout mice
    Scientific Reports, 2016
    Co-Authors: Zhen Puyang, Xiaorong Liu, Liang Feng, John B Troy, Hui Chen, Peiji Liang
    Abstract:

    The NLRP3 inflammasome, a sensor for a variety of pathogen- and host-derived threats, consists of the adaptor ASC (Apoptosis-associated Speck-like protein containing a Caspase Activation and Recruitment Domain (CARD)), pro-caspase-1, and NLRP3 (NOD-Like Receptor family Pyrin domain containing 3). NLRP3-induced neuroinflammation is implicated in the pathogenesis and progression of eye diseases, but it remains unclear whether activation of NLRP3 inflammasome contributes to retinal ganglion cell (RGC) death. Here we examined NLRP3-induced neuroinflammation and RGC survival following partial optic Nerve Crush (pONC) injury. We showed that NLRP3 was up-regulated in retinal microglial cells following pONC, propagating from the injury site to the optic Nerve head and finally the entire retina within one day. Activation of NLRP3-ASC inflammasome led to the up-regulation of caspase-1 and a proinflammatory cytokine, interleukin-1β (IL-1β). In NLRP3 knockout mice, up-regulation of ASC, caspase-1, and IL-1β were all reduced, and, importantly, RGC and axon loss was substantially delayed following pONC injury. The average survival time of RGCs in NLRP3 knockout mice was about one week longer than for control animals. Taken together, our study demonstrated that ablating the NLRP3 gene significantly reduced neuroinflammation and delayed RGC loss after optic Nerve Crush injury.