The Effects of Extracellular Matrix Proteins and Stiffness on Neuronal Cell Adhesion

2011 ◽  
Author(s):  
Ross Kleiman ◽  
Michelle Previtera ◽  
Sharan Parikh ◽  
Devendra Verma ◽  
Rene Schloss ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Neuronal Cell ◽  
Collagen Gels ◽  
Collagen Matrices ◽  
Spinal Cord Neurons ◽  
Cellular Environment ◽  
Proliferation And Differentiation ◽  
Neuronal Precursor Cell

Spinal cord injuries have spurred research interests in finding ways to repair or replace damaged neurons. We are looking to find novel ways to promote proliferation and differentiation of stem cells in order to replace damaged spinal cord neurons. While previous studies have shown that the mechanical properties of the cellular environment influence proliferation and differentiation, these studies have only been performed on polyacrylamide and agarose gels (1, 2). Collagen gels provide the opportunity to promote neuronal precursor cell (NPCs) proliferation and differentiation in a more natural environment by utilizing the mechanical properties of the gel. In this study, we examine the effects of 2D collagen matrices of varying stiffness on proliferation and differentiation of rat, spinal cord NPCs in order to create a more biocompatible tissue-engineered platform.

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.

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.

Neuronal Precursor Cell Proliferation on Elastic Substrates

2011 ◽  
Author(s):  
Michelle L. Previtera ◽  
Mason Hui ◽  
Malav Desai ◽  
Devendra Verma ◽  
Rene Schloss ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Precursor Cell ◽  
Injured Spinal Cord ◽  
Spinal Cord Neuron ◽  
Neuronal Precursor ◽  
Cord Injury ◽  
Proliferation And Differentiation ◽  
Elastic Substrates ◽  
Cord Neuron ◽  
Neuronal Precursor Cell

Numerous stem cells therapies have been studied for the replacement of damaged neurons due to spinal cord injury. Our laboratory’s goal is to design an implantable platform for spinal cord neuron (SCN) proliferation and differentiation in order to replace damaged neurons in the injured spinal cord. Based on previous literature, we suspect we can promote neuronal precursor cell (NPC) proliferation and differentiation utilizing elastic matrices.

Spinal Cord Neuronal Cell Properties Respond Differentially to the Stiffness of DNA Crosslinked Hydrogels

2008 ◽  
Author(s):  
Frank X. Jiang ◽  
Penelope Georges ◽  
Uday Chippada ◽  
Lulu Li ◽  
Bernard Yurke ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Central Nervous System ◽  
Neuronal Cell ◽  
Neural Tissue ◽  
Cell Types ◽  
Extracellular Matrices ◽  
Neural Tissue Engineering ◽  
Cord Injury ◽  
Cns Neurons

Mechanical cues arising from extracellular matrices greatly affect cellular properties, and hence, are of significance in designing biomaterials. Similar to many other cell types, including fibroblasts and hepatocytes, central nervous system (CNS) neurons have been found to exhibit distinct responses to the stiffness of the substrates they reside on [1]. There is an increasing awareness that mechanical properties also play a key role in successful utilization of scaffolds for those tissues whose major functions are not load-bearing, such as the spinal cord. In light of this, there is a growing interest in incorporating mechanical cues in biomaterial design for neural tissue engineering applications, including spinal cord injury.

Mechanical Properties of the Fetal Bovine Bladder Lamina Propria and Their Correlation With Changes in Extracellular Matrix

2008 ◽  
Author(s):  
Robert S. Cargill ◽  
Kevin K. Toosi ◽  
Edward J. Macarak
Keyword(s):  
Mechanical Properties ◽  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Low Pressure ◽  
Posterior Urethral Valves ◽  
Back Pressure ◽  
Dysfunctional Voiding ◽  
Urethral Valves ◽  
Fetal Bovine ◽  
Increased Pressure

The urinary bladder is an organ whose purpose is to store urine at low pressure and periodically expel it. This system normally operates at relatively low pressure to protect the kidneys from the deleterious effects of increased pressure. In certain pathologies, this organ can be subject to a decrease in compliance (“stiffening”) and an increase of the storage pressure which causes higher back pressure on the kidney and ultimately results in kidney damage if untreated. Clinically, these pathologies are exemplified in disorders such as myelomeningocele, posterior urethral valves, dysfunctional voiding, and disorders associated with spinal cord injuries. In these disorders, bladder structure is altered and the bladder becomes stiff and noncompliant.

scholarly journals A few axonal proteins distinguish ventral spinal cord neurons from dorsal root ganglion neurons.

1984 ◽  
Vol 98 (1) ◽  
pp. 364-368 ◽  
Author(s):  
P Sonderegger ◽  
M C Fishman ◽  
M Bokoum ◽  
H C Bauer ◽  
E A Neale ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root Ganglia ◽  
Dorsal Root ◽  
Synapse Formation ◽  
Neuronal Cell ◽  
Dorsal Root Ganglion Neurons ◽  
Neuronal Diversity ◽  
Spinal Cord Neurons ◽  
Ganglion Neurons ◽  
Ventral Spinal Cord

A series of proteins putatively involved in the generation of axonal diversity was identified. Neurons from ventral spinal cord and dorsal root ganglia were grown in a compartmented cell-culture system which offers separate access to cell somas and axons. The proteins synthesized in the neuronal cell somas and subsequently transported into the axons were selectively analyzed by 2-dimensional gel electrophoresis. The patterns of axonal proteins were substantially less complex than those derived from the proteins of neuronal cell bodies. The structural and functional similarity of axons from different neurons was reflected in a high degree of similarity of the gel pattern of the axonal proteins from sensory ganglia and spinal cord neurons. Each axonal type, however, had several proteins that were markedly less abundant or absent in the other. These neuron-population enriched proteins may be involved in the implementation of neuronal diversity. One of the proteins enriched in dorsal root ganglia axons had previously been found to be expressed with decreased abundance when dorsal root ganglia axons were co-cultured with ventral spinal cord cells under conditions in which synapse formation occurs (P. Sonderegger, M. C. Fishman, M. Bokoum, H. C. Bauer, and P.G. Nelson, 1983, Science [Wash. DC], 221:1294-1297). This protein may be a candidate for a role in growth cone functions, specific for neuronal subsets, such as pathfinding and selective axon fasciculation or the initiation of specific synapses. The methodology presented is thus capable of demonstrating patterns of protein synthesis that distinguish different neuronal subsets. The accessibility of these proteins for structural and functional studies may contribute to the elucidation of neuron-specific functions at the molecular level.

Impairment Rating and Spinal Cord Injuries: Revisiting the Guides

2010 ◽  
Vol 15 (3) ◽  
pp. 1-7
Author(s):  
Richard T. Katz
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injuries ◽  
Functional Independence ◽  
Outcome Data ◽  
Multiple Organ ◽  
Loss Of Function ◽  
Sixth Edition ◽  
Organ Systems ◽  
Cord Injury ◽  
Impairment Ratings

Abstract This article addresses some criticisms of the AMA Guides to the Evaluation of Permanent Impairment (AMA Guides) by comparing previously published outcome data from a group of complete spinal cord injury (SCI) persons with impairment ratings for a corresponding level of injury calculated using the AMA Guides, Sixth Edition. Results of the comparison show that impairment ratings using the sixth edition scale poorly with the level of impairments of activities of daily living (ADL) in SCI patients as assessed by the Functional Independence Measure (FIM) motor scale and the extended FIM motor scale. Because of the combinations of multiple impairments, the AMA Guides potentially overrates the impairment of paraplegics compared with that of quadriplegics. The use and applicability of the Combined Values formula should be further investigated, and complete loss of function of two upper extremities seems consistent with levels of quadriplegia using the SCI model. Some aspects of the AMA Guides contain inconsistencies. The concept of diminishing impairment values is not easily translated between specific losses of function per organ system and “overall” loss of ADLs involving multiple organ systems, and the notion of “catastrophic thresholds” involving multiple organ systems may support the understanding that variations in rating may exist in higher rating cases such as those that involve an SCI.

Spinal Impairment Evaluation: Fifth Edition Changes

2001 ◽  
Vol 6 (1) ◽  
pp. 1-3
Author(s):  
Robert H. Haralson
Keyword(s):  
Spinal Cord ◽  
Lower Extremity ◽  
Range Of Motion ◽  
Upper Extremity ◽  
Spinal Cord Injuries ◽  
Clinical Findings ◽  
Fourth Edition ◽  
Treatment Results ◽  
Standard Terminology ◽  
Made In

Abstract The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth Edition, was published in November 2000 and contains major changes from its predecessor. In the Fourth Edition, all musculoskeletal evaluation and rating was described in a single chapter. In the Fifth Edition, this information has been divided into three separate chapters: Upper Extremity (13), Lower Extremity (14), and Spine (15). This article discusses changes in the spine chapter. The Models for rating spinal impairment now are called Methods. The AMA Guides, Fifth Edition, has reverted to standard terminology for spinal regions in the Diagnosis-related estimates (DRE) Method, and both it and the Range of Motion (ROM) Method now reference cervical, thoracic, and lumbar. Also, the language requiring the use of the DRE, rather than the ROM Method has been strengthened. The biggest change in the DRE Method is that evaluation should include the treatment results. Unfortunately, the Fourth Edition's philosophy regarding when and how to rate impairment using the DRE Model led to a number of problems, including the same rating of all patients with radiculopathy despite some true differences in outcomes. The term differentiator was abandoned and replaced with clinical findings. Significant changes were made in evaluation of patients with spinal cord injuries, and evaluators should become familiar with these and other changes in the Fifth Edition.

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