Mechanical Characterization of the Injured Spinal Cord after Lateral Spinal Hemisection Injury in the Rat

Saxena, Tarun; Gilbert, Jeremy L.; Stelzner, Dennis J.; Hasenwinkel, Julie M.

doi:10.1089/neu.2011.1818

Cited by 46 publications

(56 citation statements)

References 52 publications

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“…A more extreme example is the effect of a lesion on neural tissue. For example, the hemisection of a rat spinal cord leads to a decrease of the elastic modulus but an increase of the viscosity, measured by micro-indentation 2 and 8 weeks after injury 69 . The development of most neural implants is conducted in mammalian animal models.…”

Section: Important Features For Neural Implant Designmentioning

confidence: 99%

Materials and technologies for soft implantable neuroprostheses

2016

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| Implantable neuroprostheses are engineered systems designed to restore or substitute function for individuals with neurological deficits or disabilities. These systems involve at least one uni-or bidirectional interface between a living neural tissue and a synthetic structure, through which information in the form of electrons, ions or photons flows. Despite a few notable exceptions, the clinical dissemination of implantable neuroprostheses remains limited, because many implants display inconsistent long-term stability and performance, and are ultimately rejected by the body. Intensive research is currently being conducted to untangle the complex interplay of failure mechanisms. In this Review, we emphasize the importance of minimizing the physical and mechanical mismatch between neural tissues and implantable interfaces. We explore possible materials solutions to design and manufacture neurointegrated prostheses, and outline their immense therapeutic potential. NATURE REVIEWS | MATERIALSADVANCE ONLINE PUBLICATION | 1 REVIEWS© 2 0 1 6 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .

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Section: Important Features For Neural Implant Designmentioning

confidence: 99%

Materials and technologies for soft implantable neuroprostheses

2016

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“…The CS-GAG hydrogels displayed minimal swelling, absorbing only 6.5 ± 0.019% of their initial weight at the end of 15 days, and showed no significant loss of mass during this period ( Figure.4B). In contrast, when hydrogels were incubated with media containing 33 milliunits (mU) of hyaluronidase, they lost 51.61 ± 0.0007% of their initial weight at the end of 15 days ( Figure.4B), indicating that the CS-GAG hydrogels retained substrate specificity to the native brain enzyme hyaluronidase which is known to degrade CS-GAGs at a slower rate than CNS tissue (brain and the spinal cord) is extremely soft, with compressive moduli ranging from around 0.5 -6.5 kPa respectively [59][60][61] . Hydrogels are the scaffolding materials of choice in interventional strategies involving drug and growth factor delivery, and cell transplantation applications for CNS repair, owing to their ability to conformally fill the defect, and match the mechanical properties of CNS tissue 62,63 .…”

Section: Composition Analysis Synthesis and Characterization Of Phomentioning

confidence: 99%

Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for Neural Stem Cells

Karumbaiah

Enam²,

Brown

et al. 2015

Bioconjugate Chem.

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Neural stem cells (NSCs) possess great potential for neural tissue repair after traumatic injuries to the central nervous system (CNS). However, poor survival and self-renewal of NSCs after injury severely limits its therapeutic potential. Sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs) linked to CS proteoglycans (CSPGs) in the brain extracellular matrix (ECM) have the ability to bind and potentiate trophic factor efficacy, and promote NSC self-renewal in vivo. In this study, we investigated the potential of CS-GAG hydrogels composed of monosulfated CS-4 (CS-A), CS-6 (CS-C), and disulfated CS-4,6 (CS-E) CS-GAGs as NSC carriers, and their ability to create endogenous niches by enriching specific trophic factors to support NSC self-renewal. We demonstrate that CS-GAG hydrogel scaffolds showed minimal swelling and degradation over a period of 15 days in vitro, absorbing only 6.5 ± 0.019% of their initial weight, and showing no significant loss of mass during this period. Trophic factors FGF-2, BDNF, and IL10 bound with high affinity to CS-GAGs, and were significantly (p < 0.05) enriched in CS-GAG hydrogels when compared to unsulfated hyaluronic acid (HA) hydrogels. Dissociated rat subventricular zone (SVZ) NSCs when encapsulated in CS-GAG hydrogels demonstrated ∼88.5 ± 6.1% cell viability in vitro. Finally, rat neurospheres in CS-GAG hydrogels conditioned with the mitogen FGF-2 demonstrated significantly (p < 0.05) higher self-renewal when compared to neurospheres cultured in unconditioned hydrogels. Taken together, these findings demonstrate the ability of CS-GAG based hydrogels to regulate NSC self-renewal, and facilitate growth factor enrichment locally.

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“…Applying mechanical loads to living CNS tissue is frequently performed to measure stiffness and/or viscosity of the specimen after injury. For example, one study used a modifi ed atomic force microscope (AFM) to measure the unrelaxed elastic modulus of spinal cord tissue in anatomical regions that undergo glial scarring after traumatic SCI in rats [ 258 ]. The modulus of the spinal cord decreased at both 2 and 8 weeks post-injury at the site of the injury but the decrease was also observed across spinal levels rostral to the site of injury [ 258 ].…”

Section: Mechanical Loading To Constructs and Isolated Cell Populationsmentioning

confidence: 99%

“…For example, one study used a modifi ed atomic force microscope (AFM) to measure the unrelaxed elastic modulus of spinal cord tissue in anatomical regions that undergo glial scarring after traumatic SCI in rats [ 258 ]. The modulus of the spinal cord decreased at both 2 and 8 weeks post-injury at the site of the injury but the decrease was also observed across spinal levels rostral to the site of injury [ 258 ]. Since the degree of spreading of the cellular and biochemical changes induced by SCI correlates to the extent of pain (see Sect.…”

Section: Mechanical Loading To Constructs and Isolated Cell Populationsmentioning

confidence: 99%

Pain Biomechanics

Crosby¹,

Smith²,

Winkelstein³

2014

Accidental Injury

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Painful injury is a tremendous problem affecting a large proportion of the population during their lifetime. Pain most commonly results from trauma and/or injury, with the spine as the most common injury site for producing chronic pain. This chapter reviews relevant anatomy, mechanics and techniques used to study cervical spine pain in particular, since it is the region most prone to injury and because the largest body of research has been in this region. In vivo, many behavioral assessments exist to functionally measure painful outcomes, with hyperalgesia and allodynia as the two primary classes of behavioral responses. Both provide quantitative measures of pain that relate to the clinical presentation of symptoms. This chapter begins with a brief review of the anatomical tissues that are most at risk for injury and pain generation. This is followed by a review highlighting the cellular and molecular mechanisms of nociception and pain, addressing modifi cations in the periphery and in the central nervous system (CNS). The relationship between injury biomechanics and the local and spinal cellular responses are presented in the context of nociception and pain, with specifi c focus on injury to the facet capsule and nerve root because of their common involvement in cervical spine injury. Lastly, a brief review of experimental methodologies used to study pain biomechanics, ranging from the macroscopic to the cellular and molecular scales, is provided along with contextualization of the relative advantages and limitations of each. A brief summary integrates all of the sections to identify future areas of research that will defi ne a more detailed understanding of pain biomechanics.

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Mechanical Characterization of the Injured Spinal Cord after Lateral Spinal Hemisection Injury in the Rat

Cited by 46 publications

References 52 publications

Materials and technologies for soft implantable neuroprostheses

Materials and technologies for soft implantable neuroprostheses

Chondroitin Sulfate Glycosaminoglycan Hydrogels Create Endogenous Niches for Neural Stem Cells

Pain Biomechanics

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