Trans-spinal direct current enhances corticospinal output and stimulation-evoked release of glutamate analog, D-2,3-3H-aspartic acid

2012 ◽  
Vol 112 (9) ◽  
pp. 1576-1592 ◽  
Author(s):  
Zaghloul Ahmed ◽  
Andrzej Wieraszko
Keyword(s):  
Spinal Cord ◽  
Muscle Contraction ◽  
Direct Current ◽  
Neuronal Excitability ◽  
Spinal Cord Injuries ◽  
Low Frequency ◽  
Motor Units ◽  
Spinal Cord Neurons ◽  
Muscle Actions

Trans-spinal direct current (tsDC) stimulation is a modulator of spinal excitability and can influence cortically elicited muscle contraction in a polarity-dependent fashion. When combined with low-frequency repetitive cortical stimulation, cathodal tsDC [tsDC(−)] produces a long-term facilitation of cortically elicited muscle actions. We investigated the ability of this combined stimulation paradigm to facilitate cortically elicited muscle actions in spinal cord-injured and noninjured animals. The effect of tsDC—applied alone or in combination with repetitive spinal stimulation (rSS) on the release of the glutamate analog, D-2,3-3H-aspartate (D-Asp), from spinal cord preparations in vitro—was also tested. In noninjured animals, tsDC (−2 mA) reproducibly potentiated cortically elicited contractions of contralateral and ipsilateral muscles tested at various levels of baseline muscle contraction forces. Cortically elicited muscle responses in animals with contusive and hemisectioned spinal cord injuries (SCIs) were similarly potentiated. The combined paradigm of stimulation caused long-lasting potentiation of cortically elicited bilateral muscle contraction in injured and noninjured animals. Additional analysis suggests that at higher baseline forces, tsDC(−) application does not increase the rising slope of the muscle contraction but causes repeated firing of the same motor units. Both cathodal and anodal stimulations induced a significant increase of D-Asp release in vitro. The effect of the combined paradigm of stimulation (tsDC and rSS) on the concentration of extracellular D-Asp was polarity dependent. These results indicate that tsDC can powerfully modulate the responsiveness of spinal cord neurons. The results obtained from the in vitro preparation suggest that the changes in neuronal excitability were correlated with an increased concentration of extracellular glutamate. The combined paradigm of stimulation, used in our experiments, could be noninvasively applied to restore motor control in humans with SCI.

scholarly journals CCP1, a tubulin deglutamylase, increases survival of rodent spinal cord neurons following glutamate-induced excitotoxicity

2020 ◽  
Author(s):  
Yasmin H. Ramadan ◽  
Amanda Gu ◽  
Nicole Ross ◽  
Sara A. McEwan ◽  
Maureen M. Barr ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Intracellular Transport ◽  
Spinal Cord Injuries ◽  
Neuronal Injury ◽  
Post Translational Modification ◽  
Spinal Cord Neurons ◽  
C Elegans ◽  
Structural Support ◽  
Cytoskeletal Elements

AbstractMicrotubules (MTs) are cytoskeletal elements that provide structural support, establish morphology, and act as roadways for intracellular transport in cells. Neurons extend and must maintain long axons and dendrites to transmit information through the nervous system. Therefore, in neurons, the ability to independently regulate cytoskeletal stability and MT-based transport in different cellular compartments is essential. Post-translational modification of MTs is one mechanism by which neurons can regulate the cytoskeleton.The carboxypeptidase CCP1 negatively regulates post-translational glutamylation of MTs. We previously demonstrated that the CCP1 homolog in C. elegans is important for maintenance of cilia. In mammals, loss of CCP1, and the resulting hyperglutamylation of MTs, causes neurodegeneration. It has long been known that CCP1 expression is activated by neuronal injury; however, whether CCP1 plays a neuroprotective role after injury is unknown. Furthermore, it not yet clear whether CCP1 acts on ciliary MTs in spinal cord neurons.Using an in vitro model of excitotoxic neuronal injury coupled with shRNA-mediated knockdown of CCP1, we demonstrate that CCP1 protects neurons from excitotoxic death. Unexpectedly, excitotoxic injury reduced CCP1 expression in our system, and knockdown of CCP1 did not result in loss or shortening of cilia in cultured spinal cord neurons. Our results suggest that CCP1 acts on axonal and dendritic MTs to promote cytoskeletal rearrangements that support neuroregeneration and that enzymes responsible for glutamylation of MTs might be therapeutically targeted to prevent excitotoxic death after spinal cord injuries.

Spinal cord neurons are vulnerable to rapidly triggered kainate neurotoxicity in vitro

1995 ◽  
Vol 689 (2) ◽  
pp. 265-270 ◽  
Author(s):  
Hong-zhen Yin ◽  
David D. Park ◽  
Amy D. Lindsay ◽  
John H. Weiss
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Neurons

Biomaterials Used in Nerve Regeneration Chambers as Substrata for Spinal Cord Neurons Cultured In Vitro

1994 ◽  
pp. 437-437
Author(s):  
M. Papaxanthos ◽  
J. Koenig ◽  
A. Guilhaume ◽  
V. Darrouzet ◽  
D. Portmann ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Nerve Regeneration ◽  
Spinal Cord Neurons

Development of Polymeric Nerve Guidance Conduits That Contain Anisotropic Cues Including Aligned Microfibers and Gradients of Adsorbed Laminin-1

2008 ◽  
Vol 2 (2) ◽  
Author(s):  
Jared M. Cregg ◽  
Han Bing Wang ◽  
Michael E. Mullins ◽  
Ryan J. Gilbert
Keyword(s):  
Spinal Cord ◽  
Electrospun Fiber ◽  
Axonal Growth ◽  
Contact Guidance ◽  
Directional Growth ◽  
Spinal Cord Neurons ◽  
Neurite Extension ◽  
Cord Injury ◽  
Laminin 1

Structures that direct neurite extension are important for regeneration following spinal cord injury and peripheral nerve injury. Within the spinal cord, neurons encounter a glial scar environment that impedes regeneration. In the peripheral nervous system, endogenous regeneration cannot occur across nerve gaps greater than 2mm. Current repair strategies use guidance conduits to channel axonal growth towards distal targets. While showing promise, conduit walls do not provide a suitable environment for neuronal attachment or extension, and axonal growth within conduits remains tortuous. Hence, there is a need for development of three-dimensional (3D) structures that use contact guidance—rather than confinement—as a means of guided regeneration. Our laboratory has developed aligned, electrospun fiber matrices that have been shown to direct neurite extension in vitro. In addition, a gradient of the glycoprotein laminin-1 has been adsorbed onto aligned microfiber matrices to stimulate directional growth. These matrices were then manipulated into 3D conduit structures. Novel polymeric conduits that utilize contact guidance and contain gradients of molecules that stimulate directional growth have the potential to foster fast, directed regeneration into and through conduit structures.

Evaluation of in situ gelling chitosan-PEG copolymer for use in the spinal cord

2018 ◽  
Vol 33 (3) ◽  
pp. 435-446 ◽  
Author(s):  
Ashley E Mohrman ◽  
Mahmoud Farrag ◽  
Rachel K Grimm ◽  
Nic D Leipzig
Keyword(s):  
Spinal Cord ◽  
Polyethylene Glycol ◽  
Spinal Cord Injuries ◽  
Similar Response ◽  
Cellular Delivery ◽  
Thiolated Chitosan ◽  
Cord Injury ◽  
In Situ Gelling

The goal of the present work was to characterize a hydrogel material for localized spinal cord delivery. To address spinal cord injuries, an injectable in situ gelling system was tested utilizing a simple, effective, and rapid cross-linking method via Michael addition. Thiolated chitosan material and maleimide-terminated polyethylene glycol material were mixed to form a hydrogel and evaluated in vitro and in vivo. Three distinct thiolated chitosan precursors were made by varying reaction conditions; a modification of chitosan with Traut’s reagent (2-iminothiolane) displayed the most attractive hydrogel properties once mixed with polyethylene glycol. The final hydrogel chosen for animal testing had a swelling ratio (Q) of 57.5 ± 3.4 and elastic modulus of 378 ± 72 Pa. After confirming low cellular toxicity in vitro, the hydrogel was injected into the spinal cord of rats for 1 and 2 weeks to assess host reaction. The rats displayed no overt functional deficits due to injection following initial surgical recovery and throughout the 2-week period after for both the saline-injected sham group and hydrogel-injected group. The saline and hydrogel-injected animals both showed a similar response from ED1+ microglia and GFAP overexpression. No significant differences were found between saline-injected and hydrogel-injected groups for any of the measures studied, but there was a trend toward decreased affected area size from 1 to 2 weeks in both groups. Access to the central nervous system is limited by the blood–brain barrier for noninvasive therapies; further development of the current system for localized drug or cellular delivery has the potential to shape treatments of spinal cord injury.

scholarly journals Multifunctionalized hydrogels foster hNSC maturation in 3D cultures and neural regeneration in spinal cord injuries

2019 ◽  
Vol 116 (15) ◽  
pp. 7483-7492 ◽  
Author(s):  
Amanda Marchini ◽  
Andrea Raspa ◽  
Raffaele Pugliese ◽  
Marina Abd El Malek ◽  
Valentina Pastori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Culture Media ◽  
Three Dimensional ◽  
Cholinergic Neurons ◽  
Good Manufacturing Practice ◽  
Neural Regeneration ◽  
Neuronal Markers

Three-dimensional cell cultures are leading the way to the fabrication of tissue-like constructs useful to developmental biology and pharmaceutical screenings. However, their reproducibility and translational potential have been limited by biomaterial and culture media compositions, as well as cellular sources. We developed a construct comprising synthetic multifunctionalized hydrogels, serum-free media, and densely seeded good manufacturing practice protocol-grade human neural stem cells (hNSC). We tracked hNSC proliferation, differentiation, and maturation into GABAergic, glutamatergic, and cholinergic neurons, showing entangled electrically active neural networks. The neuroregenerative potential of the “engineered tissue” was assessed in spinal cord injuries, where hNSC-derived progenitors and predifferentiated hNSC progeny, embedded in multifunctionalized hydrogels, were implanted. All implants decreased astrogliosis and lowered the immune response, but scaffolds with predifferentiated hNSCs showed higher percentages of neuronal markers, better hNSC engraftment, and improved behavioral recovery. Our hNSC-construct enables the formation of 3D functional neuronal networks in vitro, allowing novel strategies for hNSC therapies in vivo.

scholarly journals Trophic effects of skeletal muscle extracts on ventral spinal cord neurons in vitro: separation of a protein with morphologic activity from proteins with cholinergic activity.

1985 ◽  
Vol 101 (4) ◽  
pp. 1608-1621 ◽  
Author(s):  
R G Smith ◽  
J McManaman ◽  
S H Appel
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Lectin Binding ◽  
Neurite Growth ◽  
Factor Activity ◽  
Spinal Cord Neurons ◽  
Acetylcholine Synthesis ◽  
Molecular Weights ◽  
Multiple Species

Protein factors derived from skeletal muscle separately promote neurite elongation and acetylcholine synthesis in cultured rat ventral spinal neurons. Morphologic factor activity (neurite-inducing activity) is specifically found in rat skeletal muscle and cord neuron extracts, decreases with the postnatal age of the rats from which muscle extract is prepared, and increases in rat hindlimb muscle after 5 d of denervation. Cholinergic factor activity (acetylcholine synthesis-stimulating activity) is found in extracts of rat cerebral cortex and cardiac muscle in addition to spinal cord and skeletal muscle, increases with animal age, and decreases following 5 d of denervation. Biochemically, the factors responsible for these activities differ in their lability to denaturing conditions, apparent molecular weights, isoelectric points, and lectin-binding specificities. Under reducing conditions, morphologic activity is isolated in a single acidic glycoprotein with an Mr of 35,000, while acetylcholine synthesis-stimulating activity is found in multiple species of different molecular weights. Thus, acetylcholine synthesis-promoting activities and neurite growth-promoting activity appear to reside in different molecules. Significant purification of several of these factors has been achieved.

scholarly journals Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Ying Wang ◽  
Wei Wu ◽  
Xiangbing Wu ◽  
Yan Sun ◽  
Yi P Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Targeted Delivery ◽  
Neural Circuit ◽  
Thoracic Spinal Cord ◽  
Spinal Cord Neurons ◽  
Thoracic Spinal ◽  
Virus Serotype ◽  
Cord Injury

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

Fibrin Sealant (Tissucol) as a Substratum for Spinal Cord Neurons Cultured In Vitro

1994 ◽  
pp. 438-438
Author(s):  
M. Papaxanthos ◽  
J. Koenig ◽  
J. Dupont ◽  
A. Guilhaume ◽  
J. M. Aran ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Fibrin Sealant ◽  
Spinal Cord Neurons
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