Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord

Oudega, Martin; Hao, Peng; Shang, Junkui; Haggerty, Agnes E.; Wang, Zijue; Sun, Jian; Liebl, Daniel J.; Shi, Yuan; Cheng, Liming; Duan, Hongmei; Sun, Yi; Li, Xiaoguang; Lemmon, Vance

doi:10.1016/j.expneurol.2018.11.003

Cited by 36 publications

(23 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Different neurotrophic factors have differing effects. For example, NT-3 elicits growth of CST axons, and NT-3 and NGF both promote extensive DRG-origin sensory or axon from the reticular formation and red nucleus (Houweling et al, 1998;Jakeman et al, 1998;McTigue et al, 1998;Oudega & Hagg, 1999;Namiki et al, 2000;Tuszynski et al, 2002;Blesch & Tuszynski, 2003;Shumsky et al, 2003;Zhou & Shine, 2003;Oudega et al, 2019). BDNF, by contrast, has no such effect but rather stimulates sprouting and growth of rubrospinal, reticulospinal, vestibulospinal, raphespinal and motor axons (Nakahara et al, 1996;Tuszynski et al, 1996;Grill et al, 1997;Bradbury et al, 1998;Bregman et al, 2002).…”

Section: Regeneration: Targeting Neuronal Intrinsic Mechanismsmentioning

confidence: 99%

Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem

2020

View full text Add to dashboard Cite

The recent years saw the advent of promising preclinical strategies that combat the devastating effects of a spinal cord injury (SCI) that are progressing towards clinical trials. However, individually, these treatments produce only modest levels of recovery in animal models of SCI that could hamper their implementation into therapeutic strategies in spinal cord injured humans. Combinational strategies have demonstrated greater beneficial outcomes than their individual components alone by addressing multiple aspects of SCI pathology. Clinical trial designs in the future will eventually also need to align with this notion. The scenario will become increasingly complex as this happens and conversations between basic researchers and clinicians are required to ensure accurate study designs and functional readouts.

show abstract

Section: Regeneration: Targeting Neuronal Intrinsic Mechanismsmentioning

confidence: 99%

Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem

2020

View full text Add to dashboard Cite

show abstract

“…Amongst the neuroprotective factors incorporated in hydrogels, promising results have been obtained with the delivery of neurotrophin-3 [ 263 , 264 , 265 ], nerve growth factor [ 266 ], BDNF [ 267 ], and neuregulin [ 268 ]. One of the most innovative research works in this field required a complex combinatorial system of growth factors and bio-scaffolds.…”

Section: The Role Of Scaffolds In Developing Regenerative Therapiementioning

confidence: 99%

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

Rey

Barzaghini

Nardini

et al. 2020

Cells

View full text Add to dashboard Cite

In the field of regenerative medicine applied to neurodegenerative diseases, one of the most important challenges is the obtainment of innovative scaffolds aimed at improving the development of new frontiers in stem-cell therapy. In recent years, additive manufacturing techniques have gained more and more relevance proving the great potential of the fabrication of precision 3-D scaffolds. In this review, recent advances in additive manufacturing techniques are presented and discussed, with an overview on stimulus-triggered approaches, such as 3-D Printing and laser-based techniques, and deposition-based approaches. Innovative 3-D bioprinting techniques, which allow the production of cell/molecule-laden scaffolds, are becoming a promising frontier in disease modelling and therapy. In this context, the specific biomaterial, stiffness, precise geometrical patterns, and structural properties are to be considered of great relevance for their subsequent translational applications. Moreover, this work reports numerous recent advances in neural diseases modelling and specifically focuses on pre-clinical and clinical translation for scaffolding technology in multiple neurodegenerative diseases.

show abstract

“…Slow release of NT3 from chitosan grafts appears to stimulate endogenous neurogenesis after a full transection which was associated with tissue bridges spanning the 5mm injury site, restoration of sensory and motor evoked potentials and functional hindlimb recovery 128, 129 . Importantly, most aspects of this study have been independently repeated and the results replicated 130 .…”

Section: Discussionmentioning

confidence: 71%

“…Importantly, most aspects of this study have been independently repeated and the results replicated 130 .…”

Section: Figure 16: Assessing Reorganisation Of Excitatory Afferent Imentioning

confidence: 71%

An Adeno-Associated Viral vector encoding Neurotrophin 3 injected into affected forelimb muscles modestly improves sensorimotor function after contusive mid-cervical spinal cord injury

Sydney-Smith

Megaro

Spejo

et al. 2021

Preprint

View full text Add to dashboard Cite

Traumatic spinal cord injury (SCI) in humans occurs most frequently in the cervical spine where it can cause substantial sensorimotor impairments to upper limb function. The altered input to spinal circuits below the lesion leads to maladaptive reorganisation which often leads to hyperreflexia in proprioceptive circuits. Neurotrophin 3 (NT3) is growth factor essential for the development of proprioceptive neurons. We have previously shown that following bilateral corticospinal tract axotomy, intramuscular delivery of an Adeno-Associated Viral vector encoding NT3 (AAV-NT3) induces proprioceptive circuit reorganisation linked to functional recovery. To assess its therapeutic effects following a clinically relevant bilateral C5-C6 contusion in rats, AAV-NT3 was injected intramuscularly into the dominant limb 24 hours after injury and forelimb function was assessed over 13 weeks. The injury generated hyperreflexia of a distal forelimb proprioceptive circuit. There was also loss of fine motor skills during reach-and-grasp and walking on a horizontal ladder. Ex vivo magnetic resonance imaging (MRI) revealed atrophy of the spinal cord and white matter disruption throughout the lesion site together with extensive loss of grey matter. Unexpectedly, animals treated with AAV-NT3 had a slightly smaller lesion in the regions close to the epicentre compared to PBS treated animals. Rats treated with AAV-NT3 showed subtly better performance on the horizontal ladder and transient benefits on reach-and-grasp. AAV-NT3 did not normalise hyperreflexia in a treated muscle. The treatment increased the amount of NT3 in treated muscles but, unexpectedly, serum levels were only elevated in a small subset of animals. These results show that this dose and delivery of AAV-NT3 may generate subtle improvements in locomotion but additional treatments will be required to overcome the widespread sensorimotor deficits caused by contusion injury.

show abstract

Validation study of neurotrophin-3-releasing chitosan facilitation of neural tissue generation in the severely injured adult rat spinal cord

Cited by 36 publications

References 28 publications

Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem

Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem

Advances in Tissue Engineering and Innovative Fabrication Techniques for 3-D-Structures: Translational Applications in Neurodegenerative Diseases

An Adeno-Associated Viral vector encoding Neurotrophin 3 injected into affected forelimb muscles modestly improves sensorimotor function after contusive mid-cervical spinal cord injury

Contact Info

Product

Resources

About