Transplantation Strategies for Spinal Cord Injury Based on Microenvironment Modulation

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.

scholarly journals Profiling sensory neuron microenvironment after peripheral and central axon injury reveals key pathways for neural repair

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Oshri Avraham ◽  
Rui Feng ◽  
Eric Edward Ewan ◽  
Justin Rustenhoven ◽  
Guoyan Zhao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Dorsal Root ◽  
Axon Regeneration ◽  
Cell Type ◽  
Root Injury ◽  
Cord Injury

Sensory neurons with cell bodies in dorsal root ganglia (DRG) represent a useful model to study axon regeneration. Whereas regeneration and functional recovery occurs after peripheral nerve injury, spinal cord injury or dorsal root injury is not followed by regenerative outcomes. Regeneration of sensory axons in peripheral nerves is not entirely cell autonomous. Whether the DRG microenvironment influences the different regenerative capacities after injury to peripheral or central axons remains largely unknown. To answer this question, we performed a single-cell transcriptional profiling of mouse DRG in response to peripheral (sciatic nerve crush) and central axon injuries (dorsal root crush and spinal cord injury). Each cell type responded differently to the three types of injuries. All injuries increased the proportion of a cell type that shares features of both immune cells and glial cells. A distinct subset of satellite glial cells (SGC) appeared specifically in response to peripheral nerve injury. Activation of the PPARα signaling pathway in SGC, which promotes axon regeneration after peripheral nerve injury, failed to occur after central axon injuries. Treatment with the FDA-approved PPARα agonist fenofibrate increased axon regeneration after dorsal root injury. This study provides a map of the distinct DRG microenvironment responses to peripheral and central injuries at the single-cell level and highlights that manipulating non-neuronal cells could lead to avenues to promote functional recovery after CNS injuries or disease.

QUANTIFICATION OF NEUROTROPHINS IN SKELETAL MUSCLE FOLLOWING NERVE INJURY: COMPARISON BETWEEN SPINAL CORD INJURY AND PERIPHERAL NERVE INJURY

2009 ◽  
Vol 12 (04) ◽  
pp. 205-212
Author(s):  
Yasushi Morisawa ◽  
Shinichiro Takayama ◽  
Masaya Nakamura ◽  
Toshiyasu Nakamura ◽  
Hiroyasu Ikegami ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spinal Cord ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Control Group ◽  
Rt Pcr ◽  
Injury Group ◽  
Cord Injury ◽  
And Control

Purpose: We investigated the kinematics of nerve growth factor (NGF)mRNA and brain-derived neurotrophic factor (BDNF)mRNA in a skeletal muscle following spinal cord and peripheral nerve injuries by utilizing the reverse-transcription polymerase chain reaction/high-performance liquid chromatography (RT-PCR/HPLC) method. Methods: We made mice models of spinal cord transection and sciatic nerve transection, plus sham and control groups. After RNA extraction from gastrocnemius muscle of mice, RT-PCR was done. We measured the levels of NGFmRNA and BDNFmRNA in a skeletal muscle following spinal cord and peripheral nerve injuries by utilizing the RT-PCR/HPLC method. All values are analyzed and graphed as means ±SED. Bonferroni test (Post-hoc test) was used when two values were compared. Differences were considered statistically significant when p < 0.05. Results: According to the wet muscle weight, at day 7, a significant difference was found between the peripheral lesion and control group, and at days 14 and 28, significant differences were found between the spinal and peripheral lesion and control group. According to the NGFmRNA, in the peripheral nerve injury group, the levels increased up to day 28 and when compared with the control group, the levels were significantly higher at days 14 and 28. According to the BDNFmRNA, levels at days 2, 7, 14, and 28 were significantly lower in the spinal cord injury group than in the control group. However, in peripheral nerve injury group, when compared with the control group, the levels significantly increased at days 7, 14, and 28. Conclusion: We clarified marked differences in chronological changes in neurotrophin kinetics in a skeletal muscle between spinal cord injury and peripheral nerve injury.

scholarly journals SUR1, newly expressed in astrocytes, mediates neuropathic pain in a mouse model of peripheral nerve injury

2021 ◽  
Vol 17 ◽  
pp. 174480692110066
Author(s):  
Orest Tsymbalyuk ◽  
Volodymyr Gerzanich ◽  
Aaida Mumtaz ◽  
Sanketh Andhavarapu ◽  
Svetlana Ivanova ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Peripheral Nerve ◽  
Dorsal Horn ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Thermal Sensitivity ◽  
Gradual Improvement ◽  
Pain Behaviors

Background Neuropathic pain following peripheral nerve injury (PNI) is linked to neuroinflammation in the spinal cord marked by astrocyte activation and upregulation of interleukin 6 (IL -6 ), chemokine (C-C motif) ligand 2 (CCL2) and chemokine (C-X-C motif) ligand 1 (CXCL1), with inhibition of each individually being beneficial in pain models. Methods Wild type (WT) mice and mice with global or pGfap-cre- or pGFAP-cre/ERT2-driven Abcc8/SUR1 deletion or global Trpm4 deletion underwent unilateral sciatic nerve cuffing. WT mice received prophylactic (starting on post-operative day [pod]-0) or therapeutic (starting on pod-21) administration of the SUR1 antagonist, glibenclamide (10 µg IP) daily. We measured mechanical and thermal sensitivity using von Frey filaments and an automated Hargreaves method. Spinal cord tissues were evaluated for SUR1-TRPM4, IL-6, CCL2 and CXCL1. Results Sciatic nerve cuffing in WT mice resulted in pain behaviors (mechanical allodynia, thermal hyperalgesia) and newly upregulated SUR1-TRPM4 in dorsal horn astrocytes. Global and pGfap-cre-driven Abcc8 deletion and global Trpm4 deletion prevented development of pain behaviors. In mice with Abcc8 deletion regulated by pGFAP-cre/ERT2, after pain behaviors were established, delayed silencing of Abcc8 by tamoxifen resulted in gradual improvement over the next 14 days. After PNI, leakage of the blood-spinal barrier allowed entry of glibenclamide into the affected dorsal horn. Daily repeated administration of glibenclamide, both prophylactically and after allodynia was established, prevented or reduced allodynia. The salutary effects of glibenclamide on pain behaviors correlated with reduced expression of IL-6, CCL2 and CXCL1 by dorsal horn astrocytes. Conclusion SUR1-TRPM4 may represent a novel non-addicting target for neuropathic pain.

scholarly journals AAV2-mediated and hypoxia response element-directed expression of bFGF in neural stem cells showed therapeutic effects on spinal cord injury in rats

2021 ◽  
Vol 12 (3) ◽  
Author(s):  
Sipin Zhu ◽  
Yibo Ying ◽  
Jiahui Ye ◽  
Min Chen ◽  
Qiuji Wu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Clinical Trials ◽  
Control Group ◽  
Therapeutic Effects ◽  
Hypoxia Response Element ◽  
Neurofilament Protein ◽  
Response Element ◽  
Hypoxia Response ◽  
Cord Injury

AbstractNeural stem cell (NSCs) transplantation has been one of the hot topics in the repair of spinal cord injury (SCI). Fibroblast growth factor (FGF) is considered a promising nerve injury therapy after SCI. However, owing to a hostile hypoxia condition in SCI, there remains a challenging issue in implementing these tactics to repair SCI. In this report, we used adeno-associated virus 2 (AAV2), a prototype AAV used in clinical trials for human neuron disorders, basic FGF (bFGF) gene under the regulation of hypoxia response element (HRE) was constructed and transduced into NSCs to yield AAV2-5HRE-bFGF-NSCs. Our results showed that its treatment yielded temporally increased expression of bFGF in SCI, and improved scores of functional recovery after SCI compared to vehicle control (AAV2-5HRE-NSCs) based on the analyses of the inclined plane test, Basso–Beattie–Bresnahan (BBB) scale and footprint analysis. Mechanistic studies showed that AAV2-5HRE-bFGF-NSCs treatment increased the expression of neuron-specific neuronal nuclei protein (NeuN), neuromodulin GAP43, and neurofilament protein NF200 while decreased the expression of glial fibrillary acidic protein (GFAP) as compared to the control group. Further, the expressions of autophagy-associated proteins LC3-II and Beclin 1 were decreased, whereas the expression of P62 protein was increased in AAV2-5HRE-bFGF-NSCs treatment group. Taken together, our data indicate that AAV2-5HRE-bFGF-NSCs treatment improved the recovery of SCI rats, which is accompanied by evidence of nerve regeneration, and inhibition of SCI-induced glial scar formation and cell autophagy. Thus, this study represents a step forward towards the potential use of AAV2-5HRE-bFGF-NSCs for future clinical trials of SCI repair.

Expresion of thymosin (TB-4) in central glia of rat spinal cord following peripheral nerve injury

1994 ◽  
Vol 19 ◽  
pp. S146
Author(s):  
Koujiro Tohyama ◽  
Tetsuro Morita ◽  
Noboru Sato ◽  
Hiroyuki Yaginuma ◽  
Yasuo Uchiyama
Keyword(s):  
Spinal Cord ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Peripheral Nerve Injury ◽  
Rat Spinal Cord
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