Protective effects of extract of Ginkgo biloba (EGb 761) on nerve cells after spinal cord injury in rats

Abstract Background Spinal cord injury (SCI) is associated with health burden both at personal and societal levels. Recent assessments on the role of lncRNAs in SCI regulation have matured. Therefore, to comprehensively explore the function of lncRNA LEF1-AS1 in SCI, there is an urgent need to understand its occurrence and development. Methods Using in vitro experiments, we used lipopolysaccharide (LPS) to treat and establish the SCI model primarily on microglial cells. Gain- and loss of function assays of LEF1-AS1 and miR-222-5p were conducted. Cell viability and apoptosis of microglial cells were assessed via CCK8 assay and flow cytometry, respectively. Adult Sprague-Dawley (SD) rats were randomly divided into four groups: Control, SCI, sh-NC, and sh-LEF-AS1 groups. ELISA test was used to determine the expression of TNF-α and IL-6, whereas the protein level of apoptotic-related markers (Bcl-2, Bax, and cleaved caspase-3) was assessed using Western blot technique. Results We revealed that LncRNA LEF1-AS1 was distinctly upregulated, whereas miR-222-5p was significantly downregulated in LPS-treated SCI and microglial cells. However, LEF1-AS1 knockdown enhanced cell viability, inhibited apoptosis, as well as inflammation of LPS-mediated microglial cells. On the contrary, miR-222-5p upregulation decreased cell viability, promoted apoptosis, and inflammation of microglial cells. Mechanistically, LEF1-AS1 served as a competitive endogenous RNA (ceRNA) by sponging miR-222-5p, targeting RAMP3. RAMP3 overexpression attenuated LEF1-AS1-mediated protective effects on LPS-mediated microglial cells from apoptosis and inflammation. Conclusion In summary, these findings ascertain that knockdown of LEF1-AS1 impedes SCI progression via the miR-222-5p/RAMP3 axis.

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Systemic Administration of Fibroblast Growth Factor 21 Improves the Recovery of Spinal Cord Injury (SCI) in Rats and Attenuates SCI-Induced Autophagy

Frontiers in Pharmacology ◽

10.3389/fphar.2020.628369 ◽

2021 ◽

Vol 11 ◽

Author(s):

Sipin Zhu ◽

Yibo Ying ◽

Lin Ye ◽

Weiyang Ying ◽

Jiahui Ye ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Growth Factor ◽

Fibroblast Growth Factor ◽

Functional Recovery ◽

Nerve Cells ◽

Systemic Administration ◽

Fibroblast Growth Factor 21 ◽

Fibroblast Growth ◽

Cord Injury

Protecting the death of nerve cells is an essential tactic for spinal cord injury (SCI) repair. Recent studies show that nerve growth factors can reduce the death of nerve cells and promote the healing of nerve injury. To investigate the conducive effect of fibroblast growth factor 21 (FGF21) on SCI repair. FGF21 proteins were systemically delivered into rat model of SCI via tail vein injection. We found that administration of FGF21 significantly promoted the functional recovery of SCI as assessed by BBB scale and inclined plane test, and attenuated cell death in the injured area by histopathological examination with Nissl staining. This was accompanied with increased expression of NeuN, GAP43 and NF200, and deceased expression of GFAP. Interestingly, FGF21 was found to attenuate the elevated expression level of the autophagy marker LC3-II (microtubules associated protein 1 light chain 3-II) induced by SCI in a dose-dependent manner. These data show that FGF21 promotes the functional recovery of SCI via restraining injury-induced cell autophagy, suggesting that systemic administration of FGF21 could have a therapeutic potential for SCI repair.

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Protective effects of multiple large intravenous doses of methylprednisolone succinate on experimental spinal cord injury in rats.

The Japanese Journal of Pharmacology ◽

10.1016/s0021-5198(19)37306-8 ◽

1996 ◽

Vol 71 ◽

pp. 267

Author(s):

Shunji Nomura ◽

Hiroshi Takagi ◽

Munehiro Hashimoto

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Protective Effects ◽

Experimental Spinal Cord Injury ◽

Cord Injury

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Experimental study on the protective effects of edaravone against ischemic spinal cord injury

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2005.08.049 ◽

2005 ◽

Vol 130 (6) ◽

pp. 1586-1592 ◽

Cited By ~ 33

Author(s):

Kazuchika Suzuki ◽

Teruhisa Kazui ◽

Hitoshi Terada ◽

Kazuo Umemura ◽

Yasuhiko Ikeda ◽

...

Keyword(s):

Spinal Cord ◽

Experimental Study ◽

Spinal Cord Injury ◽

Protective Effects ◽

Cord Injury ◽

Ischemic Spinal Cord Injury

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Protective effects of glucosamine-kynurenic acid after compression-induced spinal cord injury in the rat

Open Life Sciences ◽

10.2478/s11535-012-0096-2 ◽

2012 ◽

Vol 7 (6) ◽

pp. 996-1004 ◽

Cited By ~ 1

Author(s):

Andrea Korimová ◽

Dáša Cížková ◽

Jozsef Toldi ◽

László Vécsei ◽

Ivo Vanický

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Amino Acid ◽

Kynurenic Acid ◽

Excitatory Amino Acid ◽

Protective Effects ◽

Tissue Destruction ◽

Amino Acid Receptors ◽

Cord Injury ◽

Secondary Tissue

AbstractKynurenic acid (KYNA), a metabolite of the essential amino acid L-tryptophan, is a broad spectrum antagonist of excitatory amino acid receptors, which have also anticonvulsant and neuroprotective properties. After spinal cord injury (SCI), excitotoxicity is considered to play a significant role in the processes of secondary tissue destruction in both grey and white matter of the spinal cord. In this study, we have tested the potential therapeutic effect of glucosamine-kynurenic acid, administered after experimental compression-induced SCI in the rat. Spinal application of glucosamine-kynurenic acid continually for 24 hr after experimental SCI resulted in improved motor function recovery, beginning from the first week of evaluation and continuing until the end of the study (4 weeks). After 4 weeks’ survival, quantitative morphometric analysis of the spinal cord showed that glucosamine-kynurenic acid treatment was associated with improved tissue preservation at the lesion site. These findings indicate that spinal application of glucosaminekynurenic acid is neuroprotective and improves the outcome even when administered after spinal trauma. Our results suggest that the treatments initiated in early posttraumatic period can alleviate secondary injury and improve the final outcome after SCI.

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Methylprednisolone Induces Neuro-Protective Effects via the Inhibition of A1 Astrocyte Activation in Traumatic Spinal Cord Injury Mouse Models

Frontiers in Neuroscience ◽

10.3389/fnins.2021.628917 ◽

2021 ◽

Vol 15 ◽

Author(s):

Hong-jun Zou ◽

Shi-Wu Guo ◽

Lin Zhu ◽

Xu Xu ◽

Jin-bo Liu

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Mouse Models ◽

Neuronal Cells ◽

Neurological Function ◽

Traumatic Spinal Cord Injury ◽

Protective Effects ◽

Astrocyte Activation ◽

Cord Injury

Traumatic spinal cord injury (TSCI) leads to pathological changes such as inflammation, edema, and neuronal apoptosis. Methylprednisolone (MP) is a glucocorticoid that has a variety of beneficial effects, including decreasing inflammation and ischemic reaction, as well as inhibiting lipid peroxidation. However, the efficacy and mechanism of MP in TSCI therapy is yet to be deciphered. In the present study, MP significantly attenuated the apoptotic effects of H2O2 in neuronal cells. Western blot analysis demonstrated that the levels of apoptotic related proteins, Bax and cleaved caspase-3, were reduced while levels of anti-apoptotic Bcl-2 were increased. In vivo TUNEL assays further demonstrated that MP effectively protected neuronal cells from apoptosis after TSCI, and was consistent with in vitro studies. Furthermore, we demonstrated that MP could decrease expression levels of IBA1, Il-1α, TNFα, and C3 and suppress A1 neurotoxic reactive astrocyte activation in TSCI mouse models. Neurological function was evaluated using the Basso Mouse Scale (BMS) and Footprint Test. Results demonstrated that the neurological function of MP-treated injured mice was significantly increased. In conclusion, our study demonstrated that MP could attenuate astrocyte cell death, decrease microglia activation, suppress A1 astrocytes activation, and promote functional recovery after acute TSCI in mouse models.

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