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

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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Effects of 7,8-dihydroxycoumarin on the myelin morphological changes and PSD-95 protein expression in Balb/c mice after sciatic nerve injury

Neuroreport ◽

10.1097/wnr.0000000000001712 ◽

2021 ◽

Vol 32 (14) ◽

pp. 1198-1205

Author(s):

Huiyan Sun ◽

Qiang Li ◽

Limin Zhang ◽

Zhiyong Su ◽

Jinlong Li ◽

...

Keyword(s):

Sciatic Nerve ◽

Protein Expression ◽

Nerve Injury ◽

Morphological Changes ◽

Sciatic Nerve Injury

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Effects of brazilein on PSD-95 protein expression and neurological recovery in mice after sciatic nerve injury

Neuroscience Letters ◽

10.1016/j.neulet.2019.134547 ◽

2020 ◽

Vol 715 ◽

pp. 134547

Author(s):

Cao Jian ◽

Limin Zhang ◽

Li Jinlong ◽

Tao Bo ◽

Zhongxing Liu

Keyword(s):

Sciatic Nerve ◽

Protein Expression ◽

Nerve Injury ◽

Sciatic Nerve Injury ◽

Neurological Recovery

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Protein expression profiling during wallerian degeneration after rat sciatic nerve injury

Muscle & Nerve ◽

10.1002/mus.24082 ◽

2014 ◽

Vol 50 (1) ◽

pp. 73-78 ◽

Cited By ~ 16

Author(s):

Meiyuan Li ◽

Pingan Zhang ◽

Weimin Guo ◽

Huaiqin Li ◽

Xiaosong Gu ◽

...

Keyword(s):

Sciatic Nerve ◽

Protein Expression ◽

Nerve Injury ◽

Expression Profiling ◽

Wallerian Degeneration ◽

Sciatic Nerve Injury ◽

Rat Sciatic Nerve

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

10.20944/preprints201901.0250.v1 ◽

2019 ◽

Cited By ~ 1

Author(s):

Mitsuko Takenaga ◽

Tsutomu Ishihara ◽

Jun Niimi ◽

Akemi Hamaguchi ◽

Teita Asano ◽

...

Keyword(s):

Sciatic Nerve ◽

Nerve Injury ◽

Muscle Atrophy ◽

Weight Ratio ◽

Sciatic Nerve Injury ◽

Motor Dysfunction ◽

Control Group ◽

Muscle Weight ◽

Akt Phosphorylation ◽

Tissue Repair And Regeneration

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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4-AP-3-MeOH Promotes Structural and Functional Spontaneous Recovery in the Acute Sciatic Nerve Stretch Injury

Dose-Response ◽

10.1177/1559325819899254 ◽

2020 ◽

Vol 18 (1) ◽

pp. 155932581989925

Author(s):

Yan Chen ◽

Weidong Wang ◽

Zhimin Zhao ◽

Dong Ren ◽

Danmou Xin

Keyword(s):

Sciatic Nerve ◽

Peripheral Nerve ◽

Nerve Injury ◽

Motor Function ◽

Peripheral Nerve Injury ◽

Spontaneous Recovery ◽

Sciatic Nerve Injury ◽

Stretch Injury ◽

Injured Nerve ◽

Injury Model

Background: 4-AP-3-MeOH, a derivative of 4-aminopyridine, was developed and demonstrated to prevent nerve pulse diffusion due to myelin damage and significantly enhance axonal conduction following nerve injury. Currently, repurposing the existing drug such as 4-AP-3-MeOH to restore motor function is a promising and potential therapy of peripheral nerve injury. However, to evaluate drug effect on sciatic nerve injury is full of challenge. Methods: Sciatic functional index was used to determine and measure the walking track in the stretch injury model. Nerve conductivity was performed by electrical stimulation of a nerve and recording the compound muscle action potential. Myelin thickness and regeneration was imaged and measured with transmission electron microscopy (TEM). Results: In this study, we developed a sciatic nerve injury model to minimize the spontaneous recovery mechanism and found that 4-AP-3-MeOH not only improved walking ability of the animals but also reduced the sensitivity to thermal stimulus. More interesting, 4-AP-3-MeOH enhanced and recovered electric conductivity of injured nerve; our TEM results indicated that the axon sheath thickness was increased and myelin was regenerated, which was an important evidence to support the recovery of injured nerve conductivity with 4-AP-3-MeOH treatment. Conclusions: In summary, our studies suggest that 4-AP-3-MeOH is a viable and promising approach to the therapy of peripheral nerve injury and in support of repurposing the existing drug to restore motor function.

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