The Mechanisms of Peripheral Nerve Preconditioning Injury on Promoting Axonal Regeneration

Two major factors contribute to the failure of axonal regrowth in the central nervous system (CNS), namely, the neuronal intrinsic regenerative capacity and the extrinsic local inhibitory microenvironments. However, a preconditioning peripheral nerve lesion could substantially enhance the regeneration of central axons following a subsequent spinal cord injury. In the present review, we summarize the molecular mechanisms of the preconditioning injury effect on promoting axonal regeneration. The injury signal transduction resulting from preconditioning peripheral nerve injury regulates the RAG expression to enhance axonal regeneration. Importantly, preconditioning peripheral nerve injury triggers interactions between neurons and nonneuronal cells to amplify and maintain their effects. Additionally, the preconditioning injury impacts mitochondria, protein, and lipid synthesis. All these coordinated changes endow axonal regeneration.

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Transplantation Strategies for Spinal Cord Injury Based on Microenvironment Modulation

Current Stem Cell Research & Therapy ◽

10.2174/1574888x15666200421112622 ◽

2020 ◽

Vol 15 (6) ◽

pp. 522-530

Author(s):

Jiawei Shu ◽

Feng Cheng ◽

Zhe Gong ◽

Liwei Ying ◽

Chenggui Wang ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Peripheral Nerve ◽

Nerve Injury ◽

Autonomic Dysfunction ◽

Peripheral Nerve Injury ◽

Therapeutic Effects ◽

Permanent Damage ◽

Cord Injury ◽

Severe Motor

Spinal cord injury (SCI) is different from peripheral nerve injury; it results in devastating and permanent damage to the spine, leading to severe motor, sensory and autonomic dysfunction. SCI produces a complex microenvironment that can result in hemorrhage, inflammation and scar formation. Not only does it significantly limit regeneration, but it also challenges a multitude of transplantation strategies. In order to promote regeneration, researchers have recently begun to focus their attention on strategies that manipulate the complicated microenvironment produced by SCI. And some have achieved great therapeutic effects. Hence, reconstructing an appropriate microenvironment after transplantation could be a potential therapeutic solution for SCI. In this review, first, we aim to summarize the influential compositions of the microenvironment and their different effects on regeneration. Second, we highlight recent research that used various transplantation strategies to modulate different microenvironments produced by SCI in order to improve regeneration. Finally, we discuss future transplantation strategies regarding SCI.

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Anti-hyperalgesic and anti-allodynic effects of intrathecal nociceptin/orphanin FQ in rats after spinal cord injury, peripheral nerve injury and inflammation

Pain ◽

10.1016/s0304-3959(98)00071-2 ◽

1998 ◽

Vol 76 (3) ◽

pp. 385-393 ◽

Cited By ~ 87

Author(s):

Jing-Xia Hao ◽

Isabella S. Xu ◽

Zsuzsanna Wiesenfeld-Hallin ◽

Xiao-Jun Xu

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Orphanin Fq ◽

Cord Injury

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Sortilins in neuropathic pain

Scandinavian Journal of Pain ◽

10.1016/j.sjpain.2012.05.028 ◽

2012 ◽

Vol 3 (3) ◽

pp. 183-184

Author(s):

M. Richner ◽

O.J. Bjerrum ◽

Y. De Koninck ◽

A. Nykjaer ◽

C.B. Vaegter

Keyword(s):

Spinal Cord ◽

Neuropathic Pain ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Mechanical Allodynia ◽

Molecular Mechanisms ◽

Intrathecal Injection ◽

Ion Concentration ◽

Down Regulation

AbstractBackground/aimsThe molecular mechanisms underlying neuropathic pain are incompletely understood, but recent data suggest that down-regulation of the chloride extruding co-transporter KCC2 in spinal cord sensory neurons is critical: Following peripheral nerve injury, activated microglia in the spinal cord release BDNF, which stimulates neuronal TrkB receptors and ultimately results in the reduction of KCC2 levels. Consequently, neuronal intracellular chloride ion concentration increases, impairing GABAA-receptor mediated inhibition. We have previously described how the receptor sortilin modulates neurotrophin signaling by facilitating anterograde transport of Trk receptors. Unpublished data further link SorCS2, another member of the Sortilins family of sorting receptors (sortilin, SorLA and SorCS1–3) to BDNF signaling by regulating presynaptic TrkB trafficking. The purpose of this study is to explore the involvement of Sortilins in neuropathic pain.MethodsWe subjected wild-type (wt), sortilin knockout (Sort1-/-) and SorCS2 knockout (SorCS2-/-) mice to the Spared Nerve Injury (SNI) model of peripheral nerve injury. Mechanical allodynia was measured by von Frey filaments using the up-down-up method and a 3-out-of-5 thresshold.ResultsAs previously described by several groups, wt mice developed significant mechanical allodynia following SNI. Interestingly however, mice lacking sortilin or SorCS2 were fully protected from development of allodynia and did not display KCC2 down-regulation following injury. In addition, a single intrathecal injection of antibodies against sortilin or SorCS2 could delay or rescue mechanical allodynia in wt SNI mice for 2-3 days. Finally, neither sortilin nor SorCS2 deficient mice responded to intrathecal injection of BDNF, in contrast to wt mice which developed transient mechanical allodynia.ConclusionWe hypothesize that sortilin and SorCS2 are involved in neuropathic pain development by regulating TrkB signaling. Alternatively, Sortilins may directly influence the regulation of KCC2 membrane levels following injury. Both hypotheses are currently being investigated by our group.

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