Nano PGE1 Enhances Phosphorylation of ERK1/2 and Akt to Promote Recovery from Motor Dysfunction and Muscle Atrophy Induced by Sciatic Nerve Injury

The effect of prostaglandin E1 (PGE1) encapsulated in nanoparticles (Nano PGE1) on motor dysfunction and muscle atrophy induced by sciatic nerve injury (SNI) was investigated in rats, and was compared with PGE1 encapsulated in lipid microspheres (Lipo PGE1) or PGE1 clathrated in cyclodextrin (PGE1-CD). The hind limb muscle weight ratio decreased until 2 weeks after SNI. All 3 PGE1 formulations significantly improved SNI-induced motor dysfunction. Nano PGE1 significantly promoted recovery from muscle atrophy at 2 and 3 weeks after SNI. Lipo PGE1 was also effective, but multiple doses were required. Compared with the SNI control group, the Nano PGE1 group showed upregulation of vascular endothelial growth factor (VEGF) and agrin expression in the injured sciatic nerve and atrophic muscles. Nano PGE1 accumulated prominently at the site of nerve injury and persisted for longer than Lipo PGE1 or PGE1-CD. Expression of all EP receptors was detected in the normal sciatic nerve, and EP2 expression increased after SNI. Finally, Nano PGE1 promoted ERK1/2 and Akt phosphorylation. These findings suggest that PGE1 released from nanoparticles accumulates at sites of nerve injury and increases VEGF production by augmenting ERK1/2 phosphorylation via EP receptor signaling, thus promoting tissue repair and regeneration.

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Functional and electron-microscopic changes after differential traction injury in the sciatic nerve of a rat

Maxillofacial Plastic and Reconstructive Surgery ◽

10.1186/s40902-021-00297-4 ◽

2021 ◽

Vol 43 (1) ◽

Author(s):

Soo-Hwan Byun ◽

Kang-Min Ahn

Keyword(s):

Sciatic Nerve ◽

Weight Ratio ◽

Control Group ◽

Muscle Weight ◽

Traction Injury ◽

Fiber Number ◽

Group A ◽

Myelin Thickness ◽

Group B ◽

G Ratio

Abstract Background During maxillofacial trauma or oral cancer surgery, peripheral nerve might be damaged by traction injury. The purpose of this study was to evaluate functional and histomorphometric changes after traction nerve injury in the sciatic nerve of a rat model. Methods A total of 24 Sprague-Dawley rats were equally divided into three groups: unstretched (sham/control, group A), stretched with 0.7N (group B) and 1.5N (group C). Traction injury was performed for 10 min in B and C groups. Functional recovery of the sciatic nerve was evaluated by walking track analysis, toe spread test, and pinprick test 2 weeks after injury. The weight of gastrocnemius muscles of both sides was measured to evaluate weight ratio (ipsilateral/contralateral). Total number of axons, axon fiber size, myelin thickness, G-ratio, axon number/mm2, diameter of fiber, changes of longitudinal width, and formation of the edema and hematoma were evaluated by transmission electron microscopy. Results The sciatic function indexes were −11.48±4.0, −15.11±14.84, and −49.12±35.42 for groups A, B, and C, respectively. Pinprick test showed 3.0, 2.86±0.38, and 1.38±0.52 for A, B, and group C. Muscle weight ratios were 0.98±0.13 for group A, 0.70±0.10 for group B, and 0.54±0.05 for group C. There were significant differences in toe spread test, pinprick test, and muscle weight ratio between control group and experimental group (p<0.001). In the experimental group, fiber number, fiber size, G-ratio, fiber number/mm2, myelin thickness, diameter of fiber, and longitudinal width were decreased with statistical significance. Conclusion The present study demonstrated that the nerve traction injury in the rat sciatic nerve damaged the motor and sensory function and axonal integrity. The amount of functional nerve damage was proportional to the amount of traction power and dependent on the initial tensile strengths (0.7N and 1.5N).

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Electrical stimulation by semi-implantable electrodes decreases the levels of proteins associated with sciatic nerve injury-induced muscle atrophy

Molecular Medicine Reports ◽

10.3892/mmr.2013.1487 ◽

2013 ◽

Vol 8 (1) ◽

pp. 245-249 ◽

Cited By ~ 1

Author(s):

JUN LIU ◽

KUANGWEN LI ◽

XIONGJIE HUANG ◽

JUNFENG XIE ◽

XINFENG HUANG

Keyword(s):

Electrical Stimulation ◽

Sciatic Nerve ◽

Nerve Injury ◽

Muscle Atrophy ◽

Sciatic Nerve Injury ◽

Implantable Electrodes

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Effects of 7,8-dihydroxycoumarin on the Myelin Morphological Changes and PSD-95 Protein Expression in Balb/c Mice after Sciatic Nerve Injury

10.1101/529917 ◽

2019 ◽

Author(s):

Jian Cao ◽

Limin Zhang ◽

Jinlong Li ◽

Hui Leng

Keyword(s):

Sciatic Nerve ◽

Protein Expression ◽

Nerve Injury ◽

Morphological Changes ◽

Sciatic Nerve Injury ◽

Dose Effect ◽

Control Group ◽

Male Adult ◽

Effect Relationship ◽

Injured Nerve

AbstractTo investigate the effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in mice with sciatic nerve injury, and to explore the relationship between PSD-95 protein and myelin regeneration after nerve myelin injury. 127 male adult Balb/c mice were selected and randomly divided into high, medium and low 7,8-dihydroxycoumarin dose groups and blank control group. Anastomosis was then carried out for the amputated right sciatic nerve, and intraperitoneal injection of 7,8-dihydroxycoumarin was applied postoperatively. At weeks 1, 2, 4 and 8 after surgery, nervous tissues from the injury side were taken for immunohistochemical Luxol Fast Blue (LFB) staining, so as to observe the morphological changes of the locally injured nerve myelin. Meanwhile, PSD-95 mRNA and protein expression were determined using real-time PCR and western blotting. The nerve myelin recovery in injury side of mice at all time points showed a definite dose-effect relationship with the dose of 7,8-dihydroxycoumarin. Moreover, 7,8-dihydroxycoumarin could inhibit the PSD-95 mRNA level and protein expression. At the same time, there was a dose-effect of the inhibition. 7,8-dihydroxycoumarin can affect nerve recovery in mice with sciatic nerve injury, which shows a definite dose-effect relationship with its dose. Besides, PSD-95 protein expression can suppress the regeneration of the injured nerve myelin.

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Transcriptomic Analysis Reveals PTBP1 as a Key Molecular Signature of Sciatic Nerve Injury Recovery

10.21203/rs.3.rs-166941/v1 ◽

2021 ◽

Author(s):

Zijia Chai ◽

Jinjin Fu ◽

Zhe Yang ◽

Yi E. Sun

Keyword(s):

Sciatic Nerve ◽

Nerve Injury ◽

Early Stage ◽

Sciatic Nerve Injury ◽

Sensory Function ◽

Molecular Signature ◽

Control Group ◽

P Value ◽

Immunofluorescence Test ◽

Hub Genes

Abstract Background: Peripheral nerves control motor, sensory, and autonomic functions, so injury can seriously affect a patient's quality of life. There have been studies that have shown that the repair factors are different at different ages, and we have identified a repair hub gene that plays a key role throughout the entire age group. Methods: From Gene Expression Omnibus database GSE4090, mice of 2 and 24 months of age after sciatic nerve injury were selected from mice transcriptome data of differentially expressed genes in common, and the hub genes were then determined using protein-protein network and MCODE analysis, DAVID biological process, molecular function, and cell component analysis, and the miRWalk analysis of hub genes was performed to verify the key molecule. In mice aged eight weeks of sciatic 2 nerve clamps damage building, on days 0, 1, 4, and 7, sciatic nerve motor and sensory function were evaluated, and sciatic nerve immunofluorescence test was performed to verify PTBP1 expression. The continuous data were expressed as the mean ±SD. An independent t-test was used to compare two groups. A p-value of less than 0.05 was considered statistically significant. Results: Bioinformatics analysis showed that PTBP1 is one of the key molecules in mouse sciatic nerve repair after injury. The immunofluorescence test verified that the number of positive cells reached a maximum value of 30.6 ±6.4/ROI on day 7 after injury and a minimum value of 17.4 ±7.0/ROI in the control group (p<0.001). However, the percentage of PTBP1 positive cells reached a peak of 90.8 ±16.9% at the early stage of injury, i.e., the first day, and then dropped to a minimum of 75.7 ±8.9% on the seventh day in the animal experiment as the repair time gradually increased (p<0.05). Conclusions: PTBP1 plays a key role in the repair of sciatic nerve injury, providing a new strategy for clinical treatment of patients of all ages.

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Calpain 3 Expression Pattern during Gastrocnemius Muscle Atrophy and Regeneration Following Sciatic Nerve Injury in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms161126003 ◽

2015 ◽

Vol 16 (11) ◽

pp. 26927-26935 ◽

Cited By ~ 8

Author(s):

Ronghua Wu ◽

Yingying Yan ◽

Jian Yao ◽

Yan Liu ◽

Jianmei Zhao ◽

...

Keyword(s):

Sciatic Nerve ◽

Nerve Injury ◽

Expression Pattern ◽

Muscle Atrophy ◽

Gastrocnemius Muscle ◽

Sciatic Nerve Injury ◽

Calpain 3

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Effects of Adipose-Derived Mesenchymal Stem Cells and Human Amniotic Membrane on Sciatic Nerve Repair in Rats

Archives of Neuroscience ◽

10.5812/ans.118661 ◽

2021 ◽

Vol 8 (3) ◽

Author(s):

Siyawash Xaki ◽

Afshin Fathi ◽

Mehdi Ariana ◽

Hamid Reza Aghayan ◽

Babak Arjmand ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Sciatic Nerve ◽

Nerve Injury ◽

Amniotic Membrane ◽

Nerve Fibers ◽

Sciatic Nerve Injury ◽

Control Group ◽

Human Amniotic Membrane

Background: Peripheral nerve injuries remain a great challenge for microsurgery despite the significant progress in recent decades. The current gold standard is autogenous nerve grafting with a success rate as low as 50% in long gaps. Current studies have focused on finding alternative methods for bridging nerve defects. Previous data have demonstrated the role of human amniotic membrane in stimulating neural regeneration. On the other hand, adipose-derived mesenchymal stem cells can differentiate into all three germ layers and could support nerve repair. The purpose of this study was to compare the role of the human amniotic membrane with and without adipose tissue stem cells in sciatic nerve injury with gap in rats. Objectives: We aimed to evaluate the effectiveness of the human amniotic membrane with and without adipose-derived mesenchymal stem cells in sciatic nerve injury with gap in rats. Methods: Twenty-four male Wistar rats in four random groups were used in our study. In the first group, the nerve gap was repaired using the inverse resected nerve segment (Control group), the second group was repaired with a human amniotic membrane (AM group), the third group was repaired with an amnion sheet with seeded adipose-derived mesenchymal stem cells (AM/ADMSCs group), and the last group was not repaired, and both stumps were sutured to muscles. Results: All the animals underwent the procedures and survived without complication. The sciatic function index and hot plate test results were significantly improved in the AM and AM/ADMSCs groups compared to the Control group (as a gold standard of care) (P>0.05). Based on histopathology findings, regenerative nerve fibers were seen in the implanted area of both AM and AM/ADMSCs groups; however, nerve fibers were surrounded by significant fibrosis (scar formation) in the AM/ADMSCs group. The axon count in the Control group was significantly higher than both experimental groups (P < 0.01). Conclusions: Our study showed the role of amniotic membrane in the promotion of nerve regeneration in sciatic nerve injury with a gap, but adding adipose-derived mesenchymal stem cells not only has no extra benefits, but also causes more tissue scar.

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Can ReGeneraTing Agents Improve Functional Recovery of Transected Peripheral Nerve through a Nerve Gap Bridged with an Artery Graft?

Journal of Reconstructive Microsurgery Open ◽

10.1055/s-0039-1692453 ◽

2019 ◽

Vol 04 (01) ◽

pp. e47-e53

Author(s):

George Alexopoulos ◽

Leonidas Pavlidis ◽

Myron Tsagarakis ◽

Alexandros Delimpaltas ◽

Antonios Tsimponis ◽

...

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Functional Recovery ◽

Weight Ratio ◽

Negative Control Group ◽

Negative Control ◽

Control Group ◽

Muscle Weight ◽

Artery Graft ◽

Significant Difference

Background The purpose of this study was to use artery grafts filled with CACIPLIQ20 and see if they promote nerve regeneration. Methods Sixty male Wistar rats were used. The rats were randomly divided into four experimental groups (n = 15): transected control group (negative control group [NCG]), sham-operated group (positive control group [SO]) artery graft group filled with saline (AG/NS), and CACIPLIQ20-treated group (AG/CACIPLIQ20). Fifteen rats were used as artery graft donors. In the SO group, the sciatic nerve was dissected from the surrounding tissues and left intact. In the NCG, AG/NS and AG/CACIPLIQ20) groups, a 10-mm gap was created in the left sciatic nerve. In the NCG group, the gap was not bridged with a graft. In the AG/NS group, the gap was bridged with a graft filled with saline. In the AG/CACIPLIQ20 group, the graft was filled with CACIPLIQ20. Walking track analysis was performed at 4, 8, 12, and 16 weeks after surgery. At 16 weeks postoperatively, the rats were sacrificed, nerve sections were harvested for histopathology analysis, and the weight ratio of the gastrocnemius muscle was measured. Results There was no significant difference in myelin sheath thickness between the AG/NS and AG/CACIPLIQ20 groups. Muscle weight in the AG/CACIPLIQ20 group was higher but not statistically significant (p = 0.168) compared with the AG/NS group. Also, AG/CACIPLIQ20 mean was better than AG/NS mean, although there was no statistically significant difference (p = 0.605). Conclusion There could be an indication that CACIPLIQ20 improves functional recovery of a transected peripheral nerve through a nerve gap bridged with an artery graft.

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Micro- and Astroglia Activity in the Spinal Cord Ventrolateral Nucleus Sciatic Nerve Injury in Rats

Cell and Tissue Biology ◽

10.1134/s1990519x20040100 ◽

2020 ◽

Vol 14 (4) ◽

pp. 263-269

Author(s):

A. A. Starinets ◽

E. L. Egorova ◽

A. A. Tyrtyshnaia ◽

I. V. Dyuisen ◽

A. N. Baryshev ◽

...

Keyword(s):

Spinal Cord ◽

Sciatic Nerve ◽

Nerve Injury ◽

Sciatic Nerve Injury ◽

Ventrolateral Nucleus

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3D-printed nerve guidance conduits multi-functionalized with canine multipotent mesenchymal stromal cells promote neuroregeneration after sciatic nerve injury in rats

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02315-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Diego Noé Rodríguez-Sánchez ◽

Giovana Boff Araujo Pinto ◽

Luciana Politti Cartarozzi ◽

Alexandre Leite Rodrigues de Oliveira ◽

Ana Livia Carvalho Bovolato ◽

...

Keyword(s):

Growth Factor ◽

Sciatic Nerve ◽

Nerve Injury ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Multipotent Mesenchymal Stromal Cells ◽

Sciatic Nerve Injury ◽

Motor Deficits ◽

3D Printed

Abstract Background Nerve injuries are debilitating, leading to long-term motor deficits. Remyelination and axonal growth are supported and enhanced by growth factor and cytokines. Combination of nerve guidance conduits (NGCs) with adipose-tissue-derived multipotent mesenchymal stromal cells (AdMSCs) has been performing promising strategy for nerve regeneration. Methods 3D-printed polycaprolactone (PCL)-NGCs were fabricated. Wistar rats subjected to critical sciatic nerve damage (12-mm gap) were divided into sham, autograft, PCL (empty NGC), and PCL + MSCs (NGC multi-functionalized with 106 canine AdMSCs embedded in heterologous fibrin biopolymer) groups. In vitro, the cells were characterized and directly stimulated with interferon-gamma to evaluate their neuroregeneration potential. In vivo, the sciatic and tibial functional indices were evaluated for 12 weeks. Gait analysis and nerve conduction velocity were analyzed after 8 and 12 weeks. Morphometric analysis was performed after 8 and 12 weeks following lesion development. Real-time PCR was performed to evaluate the neurotrophic factors BDNF, GDNF, and HGF, and the cytokine and IL-10. Immunohistochemical analysis for the p75NTR neurotrophic receptor, S100, and neurofilament was performed with the sciatic nerve. Results The inflammatory environment in vitro have increased the expression of neurotrophins BDNF, GDNF, HGF, and IL-10 in canine AdMSCs. Nerve guidance conduits multi-functionalized with canine AdMSCs embedded in HFB improved functional motor and electrophysiological recovery compared with PCL group after 12 weeks. However, the results were not significantly different than those obtained using autografts. These findings were associated with a shift in the regeneration process towards the formation of myelinated fibers. Increased immunostaining of BDNF, GDNF, and growth factor receptor p75NTR was associated with the upregulation of BDNF, GDNF, and HGF in the spinal cord of the PCL + MSCs group. A trend demonstrating higher reactivity of Schwann cells and axonal branching in the sciatic nerve was observed, and canine AdMSCs were engrafted at 30 days following repair. Conclusions 3D-printed NGCs multi-functionalized with canine AdMSCs embedded in heterologous fibrin biopolymer as cell scaffold exerted neuroregenerative effects. Our multimodal approach supports the trophic microenvironment, resulting in a pro-regenerative state after critical sciatic nerve injury in rats.

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