Bioinformatics analysis of long non-coding RNAs involved in nerve regeneration following sciatic nerve injury

Little is known about the role of epigenetic modification in axon regeneration following peripheral nerve injury. The purpose of the present study was to investigate the role of long non-coding RNAs (lncRNAs) in the regulation of axon regeneration. We used bioinformatics to perform microarray analysis and screened total 476 lncRNAs and 129 microRNAs (miRNAs) of differentially expressed genes after sciatic nerve injury in mice. lncRNA-GM4208 and lncRNA-GM30085 were examined, and the changes in lncRNA expression in the L4–L6 dorsal root ganglia (DRG) following sciatic nerve crush injury were analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The expression of lncRNAs in the DRG changed, indicating that they might be related to nerve regeneration in the DRG following peripheral nerve injury.

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Reduced Renshaw Recurrent Inhibition after Neonatal Sciatic Nerve Crush in Rats

Neural Plasticity ◽

10.1155/2014/786985 ◽

2014 ◽

Vol 2014 ◽

pp. 1-11

Author(s):

Liang Shu ◽

Jingjing Su ◽

Lingyan Jing ◽

Ying Huang ◽

Yu Di ◽

...

Keyword(s):

Spinal Cord ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Recurrent Inhibition ◽

Crush Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Nerve Crush Injury

Renshaw recurrent inhibition (RI) plays an important gated role in spinal motion circuit. Peripheral nerve injury is a common disease in clinic. Our current research was designed to investigate the change of the recurrent inhibitory function in the spinal cord after the peripheral nerve crush injury in neonatal rat. Sciatic nerve crush was performed on 5-day-old rat puppies and the recurrent inhibition between lateral gastrocnemius-soleus (LG-S) and medial gastrocnemius (MG) motor pools was assessed by conditioning monosynaptic reflexes (MSR) elicited from the sectioned dorsal roots and recorded either from the LG-S and MG nerves by antidromic stimulation of the synergist muscle nerve. Our results demonstrated that the MSR recorded from both LG-S or MG nerves had larger amplitude and longer latency after neonatal sciatic nerve crush. The RI in both LG-S and MG motoneuron pools was significantly reduced to virtual loss (15–20% of the normal RI size) even after a long recovery period upto 30 weeks after nerve crush. Further, the degree of the RI reduction after tibial nerve crush was much less than that after sciatic nerve crush indicatig that the neuron-muscle disconnection time is vital to the recovery of the spinal neuronal circuit function during reinnervation. In addition, sciatic nerve crush injury did not cause any spinal motor neuron loss but severally damaged peripheral muscle structure and function. In conclusion, our results suggest that peripheral nerve injury during neonatal early development period would cause a more sever spinal cord inhibitory circuit damage, particularly to the Renshaw recurrent inhibition pathway, which might be the target of neuroregeneration therapy.

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Augmenting Peripheral Nerve Regeneration Using Rat Hair Follicle Stem Cells (rHFSCs) in Rats

Basic and Clinical Neuroscience Journal ◽

10.32598/bcn.2021.2240.1 ◽

2021 ◽

Author(s):

Leila Beigom Hejazian ◽

◽

Zeinab Akbarnejad ◽

Fatemeh Moghani Ghoroghi ◽

Banafshe Esmaeilzade ◽

...

Keyword(s):

Stem Cells ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Hair Follicle ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Sciatic Nerve Injury ◽

Double Labeling ◽

Hair Follicle Stem Cells ◽

Follicle Stem Cells

Introduction: Nowadays, cell therapy is the most advanced treatment of peripheral nerve injury. The aim of this study was to determine the effects of transplantation of hair follicle stem cells on the regeneration of the sciatic nerve injury in rats. Methods: The bulge region of the rat whisker was isolated and cultured. Morphological and biological features of the cultured bulge cells were observed by light microscopy and immunocytochemistry methods. Percentages of CD34, K15 and Nestin cell markers expression were demonstrated by flow cytometry. Rats were randomly divided into 3 groups: Injury group, epineurium group, and epineurium-with-cell group, that rat hair follicular stem cells (rHFSCs) were injected into the site of nerve cut. HFSCs were labeled with BrdU, and double-labeling immunofluorescence was performed to study survival and differentiation of the grafted cells. After 8 weeks, electrophysiological, histological and immunocytochemical analysis assessments were performed. Results: The results of this study show that rat hair follicle stem cells are suitable for cell culture, proliferation and differentiation. The results suggest that transplantation of rat hair follicle stem cells had the potential capability of regenerating sciatic nerve injury; moreover, evidence of electrophysiology and histology show that Epineurium with cell repair was more effective than the other experimental group (p<0.05). Conclusion: The achieved results propose that hair follicle stem cell would improve axonal growth and functional recovery after peripheral nerve injury.

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Transplantation effects of dental pulp-derived cells on peripheral nerve regeneration in crushed sciatic nerve injury

Journal of Oral Science ◽

10.2334/josnusd.17-0462 ◽

2018 ◽

Vol 60 (4) ◽

pp. 526-535 ◽

Cited By ~ 2

Author(s):

Yuta Okuwa ◽

Taku Toriumi ◽

Hidenori Nakayama ◽

Tatsuaki Ito ◽

Keita Otake ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Nerve Injury ◽

Dental Pulp ◽

Peripheral Nerve Regeneration ◽

Sciatic Nerve Injury

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Neuroprotective potential of erythropoietin and darbepoetin alfa in an experimental model of sciatic nerve injury

Journal of Neurosurgery Spine ◽

10.3171/spi-07/12/645 ◽

2007 ◽

Vol 7 (6) ◽

pp. 645-651 ◽

Cited By ~ 26

Author(s):

Giovanni Grasso ◽

Francesco Meli ◽

Vincenzo Fodale ◽

Gioacchino Calapai ◽

Michele Buemi ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Darbepoetin Alfa ◽

Placebo Treatment ◽

Sciatic Nerve Injury ◽

Crush Injury ◽

Sprague Dawley ◽

Compound Muscle Action Potentials

Object The objectives of this study were to examine whether the systemic administration of recombinant human erythropoietin (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery in a rat model of sciatic nerve injury, and to compare the effects of these agents in the model. Methods Thirty male Sprague–Dawley rats received a crush injury to the left sciatic nerve and subsequently underwent either placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa. Results Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment and improving compound muscle action potentials following nerve injury. Darbepoetin alfa, however, shortened the duration of peripheral nerve recovery and facilitated recovery from the neurological and electrophysiological impairment following crush injury significantly better than rHuEPO. Examination of the footprint length factor data revealed that darbepoetin alfa–treated animals recovered preinjury function by postoperative Day 10, 4 days earlier than animals treated with rHuEPO and 11 days earlier than animals treated with placebo. Conclusions These results suggest that recovery of neurological function in a model of peripheral nerve injury is more rapid with weekly administration of darbepoetin alfa than with daily rHuEPO treatment. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy. The administration of EPO in its long-lasting recombinant forms affords significant neuroprotection in peripheral nerve injury models and may hold promise for future clinical applications.

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Lack of correlation between spinal microgliosis and long-term development of tactile hypersensitivity in two different sciatic nerve crush injury

Molecular Pain ◽

10.1177/17448069211011326 ◽

2021 ◽

Vol 17 ◽

pp. 174480692110113

Author(s):

Hyoung Woo Kim ◽

Chan Hee Won ◽

Seog Bae Oh

Keyword(s):

Spinal Cord ◽

Chronic Pain ◽

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Sensory Function ◽

Crush Injury ◽

Sciatic Nerve Crush

Microglia activation following peripheral nerve injury has been shown to contribute to central sensitization of the spinal cord for the development of neuropathic pain. In a recent study, we reported that the amount of nerve damage does not necessarily correlate with chronic pain development. Here we compared the response of spinal microglia, using immunohistochemistry as a surrogate of microglial activation, in mice with two different types of crush injury of the sciatic nerve. We confirmed that incomplete crush of the sciatic nerve (partial crush injury, PCI) resulted in tactile hypersensitivity after the recovery of sensory function (15 days after surgery), whereas the hypersensitivity was not observed after the complete crush (full crush injury, FCI). We observed that immunoreactivity for Iba-1, a microglial marker, was greater in the ipsilateral dorsal horn of lumbar (L4) spinal cord of mice 2 days after FCI compared to PCI, positively correlating with the intensity of crush injury. Ipsilateral Iba-1 reactivity was comparable between injuries at 7 days with a significant increase compared to the contralateral side. By day 15 after injury, ipsilateral Iba-1 immunoreactivity was much reduced compared to day 7 and was not different between the groups. Our results suggest that the magnitude of the early microgliosis is dependent on injury severity, but does not necessarily correlate with the long-term development of chronic pain-like hypersensitivity after peripheral nerve injury.

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Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury

Journal of Neuroinflammation ◽

10.1186/s12974-021-02108-z ◽

2021 ◽

Vol 18 (1) ◽

Author(s):

Erin-Mai F. Lim ◽

Vahid Hoghooghi ◽

Kathleen M. Hagen ◽

Kunal Kapoor ◽

Ariana Frederick ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Peripheral Nerve Injury ◽

Sciatic Nerve Crush ◽

Nerve Crush ◽

Cytokines And Chemokines ◽

Inflammatory Macrophages ◽

Nerve Crush Injury

Abstract Background Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury. Methods Sciatic nerve crush injuries were performed in age-matched Cryab knockout (Cryab−/−) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting. Results We report that (1) more pro-inflammatory CD16/32+ macrophages are present in the nerves of Cryab−/− mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-β, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro. Conclusions CRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.

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Allantoin, a Purine Metabolite, Enhances Peripheral Nerve Regeneration Following Sciatic Nerve Injury in Rats: A Stereological and Immunohistochemical Study

Journal of Chemical Neuroanatomy ◽

10.1016/j.jchemneu.2021.102002 ◽

2021 ◽

pp. 102002

Author(s):

Burcu Delibas ◽

Enis Kuruoglu ◽

Mehmet Cihan Bereket ◽

Mehmet Emin Onger

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Regeneration ◽

Nerve Injury ◽

Immunohistochemical Study ◽

Peripheral Nerve Regeneration ◽

Sciatic Nerve Injury ◽

Purine Metabolite

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An Investigation into the Rehabilitative Mechanism of Tuina in the Treatment of Sciatic Nerve Injury

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/5859298 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Taotao Lv ◽

Yanjun Mo ◽

Tianyuan Yu ◽

Yumo Zhang ◽

Shuai Shao ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Myelin Sheath ◽

Peripheral Nerve Injury ◽

Sham Group ◽

Sciatic Nerve Injury ◽

Ultrastructural Changes ◽

Rna Seq ◽

The Right

Objective. To explore the effect of tuina on the gene expression at the point of nerve injury in rats with sciatic nerve injury (SNI) and to elucidate the repair mechanism of tuina promoting the functional recovery of peripheral nerve injury. Methods. In the Sham group, the right sciatic nerve was exposed without clamping. The SNI model was established using the sciatic nerve clamp method on the right leg and then randomly divided into the SNI group and the Tuina group. Seven days after modeling, the Tuina group was treated daily with a “massage and tuina manipulation simulator” (Patent No. ZL 2007 0187403.1), which was used daily to stimulate Yinmen (BL37), Yanglingquan (GB34), and Chengshan (BL57) with point-pressing method, plucking method, and kneading method. The stimulating force was 4N, and the stimulating frequency was 60 times per minute; each method and each point were used for 1 minute, totaling 9 minutes (1 min/acupoint/method × 3 methods × 3 acupoints). Treatment was administered for 21 days, followed by a 1-day rest after the 10th treatment, for a total of 20 times of intervention. The sciatic function index (SFI) was used to evaluate the fine movements of the hind limbs of rats in each group. The ultrastructural changes at the point of nerve injury were observed by transmission electron microscopy, and the gene changes at the point of nerve injury were detected using RNA-sequencing (RNA-seq) technology. Results. Compared with the baseline, the SFI of the SNI group and the Tuina group decreased significantly at the 0th intervention (7 days after molding); compared with the SNI group, the SFI of the Tuina group increased at the 10th intervention (P<0.05) and increased significantly at the 15th and 20th intervention (P<0.01). Compared with the Sham group, the myelin sheath integrity of the sciatic nerve in the SNI group was destroyed and the myelin sheath collapsed seriously, even forming myelin sheath ball, accompanied with severe axonal atrophy and mitochondrial degeneration. The tuina intervention could significantly improve the ultrastructure of the nerve injury point, and the nerve fiber myelin sheath in the Tuina group remained intact, without obvious axonal swelling or atrophy. Atrophic thread granules could be seen in the axon, but there were no vacuolated mitochondria. RNA-seq results showed that there were differences at 221 genes at the point of nerve injury between the Tuina group and the SNI group and the differentially expressed genes (DEGs) are enriched in the biological processes related to the regulation of myocyte. Regulations include the regulation of striated muscle cell differentiation, myoblast differentiation, and myotube differentiation. Conclusion. Tuina can improve the fine motor recovery and protect the myelin integrity in rats with peripheral nerve injury, and this is achieved by changing the gene sequence at the injured point.

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