scholarly journals The Role of IL-17 Promotes Spinal Cord Neuroinflammation via Activation of the Transcription Factor STAT3 after Spinal Cord Injury in the Rat

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shaohui Zong ◽  
Gaofeng Zeng ◽  
Ye Fang ◽  
Jinzhen Peng ◽  
Yong Tao ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Hind Limb ◽  
Rating Scale ◽  
Serum Levels ◽  
Spinal Cord Tissue ◽  
Expression Levels ◽  
Stat3 Signaling ◽  
Cord Injury ◽  
Disease Stages

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.

scholarly journals Exendin-4 Plays a Protective Role in a Rat Model of Spinal Cord Injury Through SERCA2

2018 ◽  
Vol 47 (2) ◽  
pp. 617-629 ◽  
Author(s):  
Zhonglei Sun ◽  
Yingfu Liu ◽  
Xianbin Kong ◽  
Renjie Wang ◽  
Yunqiang Xu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Rating Scale ◽  
Protective Role ◽  
Female Rats ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Background/Aims: Current therapies for spinal cord injury (SCI) have limited efficacy, and identifying a therapeutic target is a pressing need. Sarcoplasmic/endoplasmic reticulum Ca2+ ATPase 2 (SERCA2) plays an important role in regulating calcium homeostasis, which has been shown to inhibit apoptosis. Exendin-4 has been shown to inhibit the apoptosis of nerve cells in SCI, which can also improve SERCA2 expression. In this study, we sought to determine whether exendin-4 plays a protective role in a rat model of SCI via SERCA2. Methods: To investigate the effects of exendin-4 on SCI, a rat model of SCI was induced by a modified version of Allen’s method. Spinal cord tissue sections from rats and western blot analysis were used to examine SERCA2 expression after treatment with the long-acting glucagon-like peptide 1 receptor exendin-4 or the SERCA2 antagonist 5(6)-carboxyfluorescein diacetate N-succinimidyl ester (CE). Locomotor function was evaluated using the Basso Beattie Bresnahan locomotor rating scale and slanting board test. Results: Cell apoptosis was increased with CE treatment and decreased with exendin-4 treatment. Upregulation of SERCA2 in female rats with SCI resulted in an improvement of motor function scores and histological changes. Conclusion: These findings suggest that exendin-4 plays a protective role in a rat model of SCI through SERCA2 via inhibition of apoptosis. Existing drugs targeting SERCA2 may be an effective therapeutic strategy for the treatment of SCI.

scholarly journals Targeting axon guidance cues for neural circuit repair after spinal cord injury

2020 ◽  
pp. 0271678X2096185
Author(s):  
Yimin Zou
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axon Guidance ◽  
Spinal Cord Injuries ◽  
Neural Circuit ◽  
Functional Restoration ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
The Many

At least two-thirds of spinal cord injury cases are anatomically incomplete, without complete spinal cord transection, although the initial injuries cause complete loss of sensory and motor functions. The malleability of neural circuits and networks allows varied extend of functional restoration in some individuals after successful rehabilitative training. However, in most cases, the efficiency and extent are both limited and uncertain, largely due to the many obstacles of repair. The restoration of function after anatomically incomplete injury is in part made possible by the growth of new axons or new axon branches through the spared spinal cord tissue and the new synaptic connections they make, either along the areas they grow through or in the areas they terminate. This review will discuss new progress on the understanding of the role of axon guidance molecules, particularly the Wnt family proteins, in spinal cord injury and how the knowledge and tools of axon guidance can be applied to increase the potential of recovery. These strategies, combined with others, such as neuroprotection and rehabilitation, may bring new promises. The recovery strategies for anatomically incomplete spinal cord injuries are relevant and may be applicable to traumatic brain injury and stroke.

The role of multiple hyperbaric oxygenation in expanding therapeutic windows after acute spinal cord injury in rats

2003 ◽  
Vol 99 (2) ◽  
pp. 198-205 ◽  
Author(s):  
Lixin Huang ◽  
Maheshkumar P. Mehta ◽  
Anil Nanda ◽  
John H. Zhang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Hyperbaric Oxygenation ◽  
Rating Scale ◽  
Therapeutic Window ◽  
Content Type ◽  
Cord Injury ◽  
Weight Drop ◽  
Fine Print

Object. Hyperbaric oxygenation (HBO) therapy has been reported to improve neurological recovery after spinal cord injury (SCI). In the present study, the authors examined whether multiple HBO therapy can expand the therapeutic window after acute SCI. Methods. Seventy rats were randomly assigned to seven groups: sham surgery; SCI without treatment; single HBO treatment beginning at 30 minutes, 3 hours, and 6 hours after SCI; and multiple HBO treatments starting at 6 and 24 hours postinjury. Mild SCI was induced by adjusting the height of a weight drop (10 g) to 6.25 mm above the exposed spinal cord. A single HBO administration was performed at 2.82 ata for 1 hour. The multiple HBO treatment modality was performed once daily for 1 week. All rats underwent behavioral testing with the Basso-Beattie-Breshnahan locomotor rating scale twice a week. Rats were killed on Day 42 postinjury and specimens comprising the lesioned area were histopathologically examined. Those rats that received single HBO intervention beginning at 30 minutes and 3 hours and those that received multiple HBO treatment starting at 6 hours following injury made significantly greater neurological recoveries than those in the nontreatment SCI group. These rats also retained more sparing tissue than controls. Conclusions. The results of this study demonstrate that multiple HBO treatments can expand the therapeutic window for acute SCI to 6 hours after injury.

scholarly journals Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1822 ◽  
Author(s):  
Liam M. Koehn ◽  
Qing Dong ◽  
Sing-Yan Er ◽  
Lachlan D. Rash ◽  
Glenn F. King ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Barrier Function ◽  
Hind Limb ◽  
Tissue Loss ◽  
Functional Improvement ◽  
Spinal Cord Tissue ◽  
Post Injury ◽  
Locomotor Function ◽  
Cord Injury

Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a “treatment window” through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies.

Acute spinal cord injury in rats should target activated autophagy

2014 ◽  
Vol 20 (5) ◽  
pp. 568-577 ◽  
Author(s):  
Hongping Hou ◽  
Lihai Zhang ◽  
Licheng Zhang ◽  
Peifu Tang
Keyword(s):  
Electron Microscopy ◽  
Spinal Cord ◽  
Caspase 3 ◽  
Potential Role ◽  
Autophagic Flux ◽  
Autophagosome Formation ◽  
Expression Levels ◽  
Cord Injury ◽  
Microscopy Images

Object Autophagy is a cellular mechanism of maintaining balance between protein synthesis and degradation; the latter can be induced by starvation and neurodegenerative disease. Spinal cord injury (SCI) induces necrosis and apoptosis. Autophagic flux has not yet been defined, especially the potential role of autophagy in relation to apoptosis in different tissue cells. The object of this study was to investigate the occurrence of autophagic flux and the potential role of autophagy and apoptosis post-SCI in rats. Methods Following creation of SCI in rats, activation of autophagic flux was detected at the protein (LC3, beclin1, and p62) and mRNA (beclin1) levels and on electron microscopy images. Distribution of LC3, colocalization of activated caspase-3, and changes in expression levels of bcl-2 and Bax were assessed to investigate the potential role of autophagy and apoptosis. Sprague-Dawley rats were used, and T9–10 hemitransection was performed. Expression levels of LC3, beclin1, p62, bcl-2, and Bax were assessed by Western blot analysis, and beclin1 mRNA levels were assessed by reverse transcription–polymerase chain reaction. Distribution of LC3 and colocalization of activated caspase-3 were analyzed by immunohistochemistry. Autophagosome formation was investigated by electron microscopy. Results The authors found a dramatic elevation in LC3 and beclin1 levels near the scar region. Using double staining, they observed that upregulation of LC3 started at 4 hours in neurons and at 3 days in astrocytes after SCI. Confocal images indicated that the percentage of neurons with apoptosis was reduced, while the percentage of astrocytes with apoptosis was high at 4 hours, 8 hours, and 1 day post-SCI but decreased sharply at 3 days. Electron microscopy images provided evidence of autophagosome formation. Elimination of p62 indicated occurrence of autophagic flux. Expression levels of bcl-2 and Bax were increased and decreased, respectively, near the injury site. Conclusions The results of this research demonstrated that autophagic flux is activated after SCI. Potentially, inhibition of apoptosis could be a target to promote neural recovery.

The Regulation of Bone Morphogenetic Protein/Smads Signaling Pathway in Spinal Cord Injury

2020 ◽  
Vol 10 (3) ◽  
pp. 323-328
Author(s):  
Zhigang Zhou ◽  
Kai Cao ◽  
Jianping Liao ◽  
Song Zhou ◽  
Liangliang Zhou ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Treatment Group ◽  
Signaling Pathway ◽  
Rating Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Spinal Cord Tissue ◽  
Cord Injury ◽  
Smad5 Mrna

The incidence of spinal cord injury (SCI) increases year by year. SCI is characterized as high disability rate and poor prognosis. BMP/Smads signaling participates in the formation of osteoblasts and renal failure. This article will explore the regulation of BMP/Smads signaling pathway in SCI. Wistar rats were divided into control group; SCI group; and BMP-2 treatment group that were treated by tail vein injection of BMP-2 antisense oligonucleotide BMP-2 phosphorothioate AODN at 30 min after modeling. Real-time PCR and Western blot were used to detect BMP-2, Smad1, and Smad5 expressions. Hematoxylin-eosin (HE) staining was applied to analyze the change of SCI in each group. Immunohistochemistry (IHC) was selected to test BMPR Ia expression. Basso, Beattie Bresnahan-cocomotor rating scale (BBB) scale and Reuter score were compared. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect TNF-α and Interleukin-2 (IL-2) expressions. Compared with the control group, BMP-2, Smad1, and Smad5 mRNA and protein expressions increased, BBB score declined, Reuter score elevated, and TNF-α and IL-2 secretion enhanced in the SCI group (P < 0.05). HE staining showed spinal cord injury, and IHC exhibited increased expression of BMPR Ia. The TGF-β treatment group significantly reduced the expressions of BMP-2, Smad1, and Smad5 mRNA and protein, increased BBB score, reduced Reuter score, and weakened the secretions of TNF-α and IL-2 (P < 0.05). HE staining demonstrated decreased reduction of spinal cord tissue and declined expression of BMPR Ia. SCI activated BMP/Smads signaling pathway, up-regulated BMPR Ia expression, and promoted inflammation. Regulation of BMP/Smads signaling pathway can downregulate BMPR Ia expression and inhibit inflammation to effectively relieve SCI.

scholarly journals Selective inhibition of ASIC1a confers functional and morphological neuroprotection following traumatic spinal cord injury

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 1822 ◽  
Author(s):  
Liam M. Koehn ◽  
Natassya M. Noor ◽  
Qing Dong ◽  
Sing-Yan Er ◽  
Lachlan D. Rash ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Barrier Function ◽  
Hind Limb ◽  
Tissue Loss ◽  
Functional Improvement ◽  
Spinal Cord Tissue ◽  
Post Injury ◽  
Locomotor Function ◽  
Cord Injury

Tissue loss after spinal trauma is biphasic, with initial mechanical/haemorrhagic damage at the time of impact being followed by gradual secondary expansion into adjacent, previously unaffected tissue. Limiting the extent of this secondary expansion of tissue damage has the potential to preserve greater residual spinal cord function in patients. The acute tissue hypoxia resulting from spinal cord injury (SCI) activates acid-sensing ion channel 1a (ASIC1a). We surmised that antagonism of this channel should provide neuroprotection and functional preservation after SCI. We show that systemic administration of the spider-venom peptide PcTx1, a selective inhibitor of ASIC1a, improves locomotor function in adult Sprague Dawley rats after thoracic SCI. The degree of functional improvement correlated with the degree of tissue preservation in descending white matter tracts involved in hind limb locomotor function. Transcriptomic analysis suggests that PcTx1-induced preservation of spinal cord tissue does not result from a reduction in apoptosis, with no evidence of down-regulation of key genes involved in either the intrinsic or extrinsic apoptotic pathways. We also demonstrate that trauma-induced disruption of blood-spinal cord barrier function persists for at least 4 days post-injury for compounds up to 10 kDa in size, whereas barrier function is restored for larger molecules within a few hours. This temporary loss of barrier function provides a “treatment window” through which systemically administered drugs have unrestricted access to spinal tissue in and around the sites of trauma. Taken together, our data provide evidence to support the use of ASIC1a inhibitors as a therapeutic treatment for SCI. This study also emphasizes the importance of objectively grading the functional severity of initial injuries (even when using standardized impacts) and we describe a simple scoring system based on hind limb function that could be adopted in future studies.

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