Repair of thoracic spinal cord injury by chitosan tube implantation in adult rats

Li, Xiaoguang; Yang, Zhaoyang; Zhang, Aifeng; Wang, Tailing; Chen, Weichang

doi:10.1016/j.biomaterials.2008.10.063

Cited by 113 publications

(83 citation statements)

References 42 publications

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“…The chitosan tubes and NT3-chitosan carriers were prepared as described previously (17,18,24), with modifications. Detailed information is provided in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

“…Biotinylated dextran amine conjugated with fluorescein [BDA-fluorescein, 10% (wt/vol) solution; Molecular Probes] was injected into eight different sites within the motor cortex to label the CST (24). Only fibers longer than 40 μm were counted (27).…”

Section: Methodsmentioning

confidence: 99%

“…Observers blinded to the treatment methods and groupings performed BBB scoring in an open field (24,30). More details are provided in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

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NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

Yang

Zhang

Duan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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177

172

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Neural stem cells (NSCs) in the adult mammalian central nervous system (CNS) hold the key to neural regeneration through proper activation, differentiation, and maturation, to establish nascent neural networks, which can be integrated into damaged neural circuits to repair function. However, the CNS injury microenvironment is often inhibitory and inflammatory, limiting the ability of activated NSCs to differentiate into neurons and form nascent circuits. Here we report that neurotrophin-3 (NT3)-coupled chitosan biomaterial, when inserted into a 5-mm gap of completely transected and excised rat thoracic spinal cord, elicited robust activation of endogenous NSCs in the injured spinal cord. Through slow release of NT3, the biomaterial attracted NSCs to migrate into the lesion area, differentiate into neurons, and form functional neural networks, which interconnected severed ascending and descending axons, resulting in sensory and motor behavioral recovery. Our study suggests that enhancing endogenous neurogenesis could be a novel strategy for treatment of spinal cord injury.spinal cord injury | NT3 | chitosan | functional recovery | endogenous neurogenesis

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“…The chitosan tubes and NT3-chitosan carriers were prepared as described previously (17,18,24), with modifications. Detailed information is provided in SI Materials and Methods.…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

Yang

Zhang

Duan

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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177

172

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“…Before the operation and at 1 d postsurgery and each week thereafter, observers who were blinded to the treatment methods and groups applied Basso-Beattie-Bresnahan (BBB) scoring in an open field to evaluate hindlimb locomotor function (10,17). BMS was used for mouse analyses.…”

Section: Methodsmentioning

confidence: 99%

“…One major challenge in the field of SCI research is the huge variability caused not only by different lesion models and animal strains, but also by even subtle changes in the exact lesion operations. Moreover, most analyses for evaluating neural repair/regeneration have been anatomic, behavioral, and sometimes electrophysiological, including extracellular recordings (1,4,10,11). These analyses are relatively low in resolution, and particularly the behavioral assays can be highly variable and subjective to errors in human judgment.…”

mentioning

confidence: 99%

Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

Duan

Zhang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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119

101

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Spinal cord injury (SCI) is considered incurable because axonal regeneration in the central nervous system (CNS) is extremely challenging, due to harsh CNS injury environment and weak intrinsic regeneration capability of CNS neurons. We discovered that neurotrophin-3 (NT3)-loaded chitosan provided an excellent microenvironment to facilitate nerve growth, new neurogenesis, and functional recovery of completely transected spinal cord in rats. To acquire mechanistic insight, we conducted a series of comprehensive transcriptome analyses of spinal cord segments at the lesion site, as well as regions immediately rostral and caudal to the lesion, over a period of 90 days after SCI. Using weighted gene coexpression network analysis (WGCNA), we established gene modules/ programs corresponding to various pathological events at different times after SCI. These objective measures of gene module expression also revealed that enhanced new neurogenesis and angiogenesis, and reduced inflammatory responses were keys to conferring the effect of NT3-chitosan on regeneration.S pinal cord injury (SCI) is a debilitating medical condition that often leads to permanent impairment of sensory and motor functions. SCI is considered almost incurable because axons in the central nervous system (CNS), unlike those in the peripheral nervous system (PNS), are believed not to regenerate. The innate ability of mature CNS neurons to regenerate is much weaker than that of PNS neurons (1). In addition, myelin debris in the injured CNS is more inhibitory toward axonal growth compared to that in the PNS (2). Moreover, the mode of immune cell infiltration and microglia activation are different in CNS versus PNS, resulting in a different cellular microenvironment, which crucially influences the outcome, i.e., PNS axons regenerate, while CNS axons do not (3).Over the years, SCI research has focused on ways to promote the long-distance growth of CNS motor axons, mainly by neutralizing inhibitory myelin components and/or changing the neuronal intrinsic program to enable better regeneration (4). Unfortunately, however, although numerous studies have been carried out following this line of strategy, no major breakthroughs translatable to therapy have been achieved. In recent years, efforts toward promoting long distance axonal growth have been complemented with alternative approaches aimed at using exogenous stem cells to generate local new neurons that form nascent relay neural networks to pass ascending and descending neurotransmission signals with or without long-distance axonal growth (5-7).SCI is a complex medical condition. The primary lesion includes the physical traumatic wounding of both white and gray matter, breakdown of the vasculature system, and acute immune reactions, which is followed by secondary lesions, such as demyelination, additional immune cell infiltration, inflammation, glial scar formation, impaired neurotransmission, and neuronal apoptosis (8). Secondary lesions are intermingled with intrinsic repair processes, including remyelina...

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Ice‐Templated Scaffolds with Microridged Pores Direct DRG Neurite Growth

Riblett

Francis

Wheatley

et al. 2012

Adv Funct Materials

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Successful spinal cord repair is thought to be promoted with hierarchically structured scaffolds. These should combine aligned porosity with additional linear features on the micrometer scale to guide axons across multiple length scales. Such scaffolds are generated through the carefully controlled directional solidification of an aqueous biopolymer solution, followed by lyophilization. Under specific freezing conditions this yields a highly regular and aligned lamellar architecture. This architecture exhibits uniform ridges of controlled height and width on the lamellar surface. These ridges run parallel to the pore axis, serving as secondary guidance features. The ridges are capable of linearly aligning 62.4% of chick dorsal root ganglia neurites to within ±10° of the ridge direction. Notably, neurites sprouting perpendicular to the ridge are guided into alignment with these microridged features.

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Repair of thoracic spinal cord injury by chitosan tube implantation in adult rats

Cited by 113 publications

References 42 publications

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

NT3-chitosan elicits robust endogenous neurogenesis to enable functional recovery after spinal cord injury

Transcriptome analyses reveal molecular mechanisms underlying functional recovery after spinal cord injury

Ice‐Templated Scaffolds with Microridged Pores Direct DRG Neurite Growth

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