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John H Martin - One of the best experts on this subject based on the ideXlab platform.
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Neuronal activity and microglial activation support corticospinal tract and proprioceptive afferent Sprouting in spinal circuits after a corticospinal system lesion.
Experimental Neurology, 2019Co-Authors: Yu-qiu Jiang, Kristine Armada, John H MartinAbstract:Abstract Spared corticospinal tract (CST) and proprioceptive afferent (PA) axons sprout after injury and contribute to rewiring spinal circuits, affecting motor recovery. Loss of CST connections post-injury results in corticospinal signal loss and associated reduction in spinal activity. We investigated the role of activity loss and injury on CST and PA Sprouting. To understand activity-dependence after injury, we compared CST and PA Sprouting after motor cortex (MCX) inactivation, produced by chronic MCX muscimol microinfusion, with Sprouting after a CST lesion produced by pyramidal tract section (PTx). Activity suppression, which does not produce a lesion, is sufficient to trigger CST axon outgrowth from the active side to cross the midline and to enter the inactivated side of the spinal cord, to the same extent as PTx. Activity loss was insufficient to drive significant CST gray matter axon elongation, an effect of PTx. Activity suppression triggered presynaptic site formation, but less than PTx. Activity loss triggered PA Sprouting, as PTx. To understand injury-dependent Sprouting further, we blocked microglial activation and associated inflammation after PTX by chronic minocycline administration after PTx. Minocycline inhibited myelin debris phagocytosis contralateral to PTx and abolished CST axon elongation, formation of presynaptic sites, and PA Sprouting, but not CST axon outgrowth from the active side to cross the midline. Our findings suggest Sprouting after injury has a strong activity dependence and that microglial activation after injury supports axonal elongation and presynaptic site formation. Combining spinal activity support and inflammation control is potentially more effective in promoting functional restoration than either alone.
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Motor cortex electrical stimulation augments Sprouting of the corticospinal tract and promotes recovery of motor function
Frontiers in Integrative Neuroscience, 2014Co-Authors: Jason B Carmel, John H MartinAbstract:The corticospinal system-with its direct spinal pathway, the corticospinal tract (CST) - is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST Sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST Sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon Sprouting that partially reconstructs the lost CST. Stimulation also leads to Sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent Sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.
Jason B Carmel - One of the best experts on this subject based on the ideXlab platform.
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Motor cortex electrical stimulation augments Sprouting of the corticospinal tract and promotes recovery of motor function
Frontiers in Integrative Neuroscience, 2014Co-Authors: Jason B Carmel, John H MartinAbstract:The corticospinal system-with its direct spinal pathway, the corticospinal tract (CST) - is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout, and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST Sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST Sprouting from the unaffected hemisphere. We discovered that 10 days of electrical stimulation of either the spared CST or motor cortex induces CST axon Sprouting that partially reconstructs the lost CST. Stimulation also leads to Sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent Sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay.
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Motor cortex electrical stimulation augments Sprouting of the corticospinal tract and promotes recovery of motor function
Frontiers Media S.A., 2014Co-Authors: Jason B Carmel, John EmartinAbstract:The corticospinal system—with its direct spinal pathway, the corticospinal tract (CST)—is the primary system for controlling voluntary movement. Our approach to CST repair after injury in mature animals was informed by our finding that activity drives establishment of connections with spinal cord circuits during postnatal development. After incomplete injury in maturity, spared CST circuits sprout and partially restore lost function. Our approach harnesses activity to augment this injury-dependent CST Sprouting and to promote function. Lesion of the medullary pyramid unilaterally eliminates all CST axons from one hemisphere and allows examination of CST Sprouting from the unaffected hemisphere. We discovered that ten days of electrical stimulation of either the spared CST or motor cortex induces CST axon Sprouting that partially reconstructs the lost CST. Stimulation also leads to Sprouting of the cortical projection to the magnocellular red nucleus, where the rubrospinal tract originates. Coordinated outgrowth of the CST and cortical projections to the red nucleus could support partial re-establishment of motor systems connections to the denervated spinal motor circuits. Stimulation restores skilled motor function in our animal model. Lesioned animals have a persistent forelimb deficit contralateral to pyramidotomy in the horizontal ladder task. Rats that received motor cortex stimulation either after acute or chronic injury showed a significant functional improvement that brought error rate to pre-lesion control levels. Reversible inactivation of the stimulated motor cortex reinstated the impairment demonstrating the importance of the stimulated system to recovery. Motor cortex electrical stimulation is an effective approach to promote spouting of spared CST axons. By optimizing activity-dependent Sprouting in animals, we could have an approach that can be translated to the human for evaluation with minimal delay
Yuji Ikegaya - One of the best experts on this subject based on the ideXlab platform.
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The Molecular and Cellular Mechanisms of Axon Guidance in Mossy Fiber Sprouting.
Frontiers in Neurology, 2018Co-Authors: Ryuta Koyama, Yuji IkegayaAbstract:The question of whether mossy fiber Sprouting is epileptogenic has not been resolved; both Sprouting-induced recurrent excitatory and inhibitory circuit hypotheses have been experimentally (but not fully) supported. Therefore, whether mossy fiber Sprouting is a potential therapeutic target for epilepsy remains under debate. Moreover, the axon guidance mechanisms of mossy fiber Sprouting have attracted the interest of neuroscientists. Sprouting of mossy fibers exhibits several uncommon axonal growth features in the basically non-plastic adult brain. For example, robust branching of axonal collaterals arises from pre-existing primary mossy fiber axons. Understanding the branching mechanisms in adulthood may contribute to axonal regeneration therapies in neuroregenerative medicine in which robust axonal re-growth is essential. Additionally, because granule cells are produced throughout life in the neurogenic dentate gyrus, it is interesting to examine whether the mossy fibers of newly generated granule cells follow the pre-existing trajectories of sprouted mossy fibers in the epileptic brain. Understanding these axon guidance mechanisms may contribute to neuron transplantation therapies, for which the incorporation of transplanted neurons into pre-existing neural circuits is essential. Thus, clarifying the axon guidance mechanisms of mossy fiber Sprouting could lead to an understanding of central nervous system (CNS) network reorganization and plasticity. Here, we review the molecular and cellular mechanisms of axon guidance in mossy fiber Sprouting by discussing mainly in vitro studies.
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Mossy Fiber Sprouting as a Potential Therapeutic Target for Epilepsy
Current Neurovascular Research, 2004Co-Authors: Ryuta Koyama, Yuji IkegayaAbstract:Hippocampal mossy fibers, axons of dentate granule cells, converge in the dentate hilus and run through a narrow area called the stratum lucidum to synapse with hilar and CA3 neurons. In the hippocampal formation of temporal lobe epilepsy patients, however, this stereotyped pattern of projection is often collapsed; the mossy fibers branch out of the dentate hilus and abnormally innervate the dentate inner molecular layer, a phenomenon that is termed mossy fiber Sprouting. Experimental studies have replicated this Sprouting in animal models of temporal lobe epilepsy, including kindling and pharmacological treatment with convulsants. Because these axon collaterals form recurrent excitatory inputs into dendrites of granule cells, the circuit reorganization is assumed to cause epileptiform activity in the hippocampus, whereas some recent studies indicate that the Sprouting is not necessarily associated with early-life seizures. Here we review the mechanisms of mossy fiber Sprouting and consider its potential contribution to epileptogenesis. Based on recent findings, we propose that the Sprouting can be regarded as a result of disruption of the molecular mechanisms underlying the axon guidance. We finally focus on the possibility that prevention of the abnormal Sprouting might be a new strategy for medical treatment with temporal lobe epilepsy.
Greg M Cole - One of the best experts on this subject based on the ideXlab platform.
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role of apolipoprotein e and estrogen in mossy fiber Sprouting in hippocampal slice cultures
Neuroscience, 1999Co-Authors: Bruce Teter, Marni E Harriswhite, Sally A Frautschy, Greg M ColeAbstract:A role for apolipoprotein E is implicated in regeneration of synaptic circuitry after neural injury. The in vitro mouse organotypic hippocampal slice culture system shows Timm's stained mossy fiber Sprouting into the dentate gyrus molecular layer in response to deafferentation of the entorhinal cortex. We show that cultures derived from apolipoprotein E knockout mice are defective in this Sprouting response; specifically, they show no Sprouting in the dorsal region of the dentate gyrus, yet retain Sprouting in the ventral region. Dorsal but not ventral Sprouting in cultures from C57B1/6J mice is increased 75% by treatment with 100 pM 17beta-estradiol; this response is blocked by both progesterone and tamoxifen. These results show that neuronal Sprouting is increased by estrogen in the same region where Sprouting is dependent on apolipoprotein E. Sprouting may be stimulated by estrogen through its up-regulation of apolipoprotein E expression leading to increased recycling of membrane lipids for use by Sprouting neurons. Estrogen and apolipoprotein E may therefore interact in their modulation of both Alzheimer's disease risk and recovery from CNS injury.
Thomas Deller - One of the best experts on this subject based on the ideXlab platform.
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maturation dependent differences in the re innervation of the denervated dentate gyrus by Sprouting associational and commissural mossy cell axons in organotypic tissue cultures of entorhinal cortex and hippocampus
Frontiers in Neuroanatomy, 2021Co-Authors: Mandy H Paul, Lars Hildebrandteinfeldt, Viktor Beeg J Moreno, Domenico Del Turco, Thomas DellerAbstract:Sprouting of surviving axons is one of the major reorganization mechanisms of the injured brain contributing to a partial restoration of function. Of note, Sprouting is maturation as well as age-dependent and strong in juvenile brains, moderate in adult and weak in aged brains. We have established a model system of complex organotypic tissue cultures to study Sprouting in the dentate gyrus following entorhinal denervation. Entorhinal denervation performed after two weeks postnatally resulted in a robust, rapid and very extensive Sprouting response of commissural/associational fibers which could be visualized using calretinin as an axonal marker. In the present study we analyzed the effect of maturation on this form of Sprouting and compared cultures denervated at two weeks postnatally with cultures denervated at four weeks postnatally. Calretinin immunofluorescence labeling as well as time-lapse imaging of virally-labeled (AAV2-hSyn1-GFP) commissural axons was employed to study the Sprouting response in aged cultures. Compared to the young cultures commissural/associational Sprouting was attenuated and showed a pattern similar to the one following entorhinal denervation in adult animals in vivo. We conclude that a maturation-dependent attenuation of Sprouting occurs also in vitro, which now offers the chance to study, understand and influence maturation-dependent differences in brain repair in these culture preparations.
