Molecular and Cellular Mechanisms of Axonal Regeneration After Spinal Cord Injury

Niekerk, Erna A. van; Tuszynski, Mark H.; Lu, Paul; Dulin, Jennifer N.

doi:10.1074/mcp.r115.053751

Cited by 57 publications

(52 citation statements)

References 233 publications

(147 reference statements)

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“…Modulation of cellular responses and function with a balance of protection over inhibitory effects in the lesion area of SCI will likely create a milieu favoring axonal regeneration. Currently, modulation largely focuses on blocking glial inhibition, stimulating nerve regeneration and cell‐based transplantation …”

Section: Discussionmentioning

confidence: 99%

“…Currently, modulation largely focuses on blocking glial inhibition, stimulating nerve regeneration and cell-based transplantation. [46][47][48][49] Recently, engineered biomaterials that mimic the physical characteristics of CNS tissue have been used to facilitate the restoration of connectivity across the lesion following SCI. These bioengineered materials also provide some favorable substrates or scaffolding for axonal regeneration.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Thermosensitive heparin‐poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury

Zhao

Jiang

Lin

et al. 2017

J Biomedical Materials Res

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Traumatic spinal cord injury (SCI) results in paraplegia or quadriplegia, and currently, therapeutic interventions for axonal regeneration after SCI are not clinically available. Animal studies have revealed that glial cell-derived neurotrophic factor (GDNF) plays multiple beneficial roles in neuroprotection, glial scarring remodeling, axon regeneration and remyelination in SCI. However, the poor physicochemical stability of GDNF, as well as its limited ability to cross the blood-spinal cord barrier, hampers the development of GDNF as an effective therapeutic intervention in clinical practice. In this study, a novel temperature-sensitive heparin-poloxamer (HP) hydrogel with high GDNF-binding affinity was developed. HP hydrogels showed a supporting scaffold for GDNF when it was injected into the lesion epicenter after SCI. GDNF-HP by orthotopic injection on lesioned spinal cord promoted the beneficial effects of GDNF on neural stem cell proliferation, reactive astrogliosis inhibition, axonal regeneration or plasticity, neuroprotection against cell apoptosis, and body functional recovery. Most interestingly, GDNF demonstrated a bidirectional regulation of autophagy, which inhibited cell apoptosis at different stages of SCI. Furthermore, the HP hydrogel promoted the inhibition of autophagy-induced apoptosis by GDNF in SCI. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2816-2829, 2017.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thermosensitive heparin‐poloxamer hydrogels enhance the effects of GDNF on neuronal circuit remodeling and neuroprotection after spinal cord injury

Zhao

Jiang

Lin

et al. 2017

J Biomedical Materials Res

View full text Add to dashboard Cite

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“…Their potent inhibitory nature has been demonstrated both in vitro , where axons preferentially grew on growth promoting substances such as laminin and avoided areas rich in CSPGs, and in vivo, where transplanted neurons extended long axons until they reached tissue with high levels of CSPGs. Various cell types express CSPGS and contribute to its deposition around the lesion site, including microglia, macrophages, pericytes, and fibroblasts …”

Section: Pathophysiology and Endogenous Repairmentioning

confidence: 99%

Combinatorial Therapies After Spinal Cord Injury: How Can Biomaterials Help?

Führmann¹,

Anandakumaran

Shoichet

2017

Adv Healthcare Materials

152

121

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Traumatic spinal cord injury (SCI) results in an immediate loss of motor and sensory function below the injury site and is associated with a poor prognosis. The inhibitory environment that develops in response to the injury is mainly due to local expression of inhibitory factors, scarring and the formation of cystic cavitations, all of which limit the regenerative capacity of endogenous or transplanted cells. Strategies that demonstrate promising results induce a change in the microenvironment at- and around the lesion site to promote endogenous cell repair, including axonal regeneration or the integration of transplanted cells. To date, many of these strategies target only a single aspect of SCI; however, the multifaceted nature of SCI suggests that combinatorial strategies will likely be more effective. Biomaterials are a key component of combinatorial strategies, as they have the potential to deliver drugs locally over a prolonged period of time and aid in cell survival, integration and differentiation. Here we summarize the advantages and limitations of widely used strategies to promote recovery after injury and highlight recent research where biomaterials aided combinatorial strategies to overcome some of the barriers of spinal cord regeneration.

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“…As these mature cells are unlikely to contribute successfully to myelin repair [6 & ], immature cells such as resident oligodendroglial precursor cells (OPCs) [7] or adult neural stem cells (aNSCs) [8,9 && ,10,11] jump in, become activated and are recruited in order to replace lost myelin sheaths and to restore axonal functionality. This regenerative potential is remarkable with the downside that myelin repair is also confronted with a number of limitations and in many instances remains inefficient or even failsmuch alike the well-known impairment of axonal regeneration in the adult CNS [12].…”

Section: Introductionmentioning

confidence: 99%