MCC950 reduces neuronal apoptosis in spinal cord injury in mice.

2020 ◽  
Vol 19 ◽  
Author(s):  
Ning He ◽  
Xiaohe Zheng ◽  
Teng He ◽  
Gerong Shen ◽  
Kunyu Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nlrp3 Inflammasome ◽  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Specific Inhibitor ◽  
Tunel Staining ◽  
Tail Flick ◽  
Severe Condition ◽  
Cord Injury

Background: Traumatic spinal cord injury (SCI) is a severe condition usually accompanied by an inflammatory process that gives rise to uncontrolled local apoptosis and a subsequent unfavorable prognosis. One reason for this unfavorable outcome could be the activation of the NLRP3 inflammasome. Objective: MCC950 is a specific inhibitor of NLRP3 that further inhibits the formation of the NLRP3 inflammasome. The purpose of this study was to determine whether the NLRP3 inflammasome was associated with the severity of local apoptosis and whether MCC950 could prevent neuronal apoptosis following SCI. Methods: In this study, primary cortical neurons were cultured in vitro. With or without pretreatment/posttreatment with MCC950, neurons were subjected to oxygen-glucose deprivation (OGD) for 2 h and then reperfusion for 20 h. Immunofluorescence was used to determine the expression of NLRP3, ASC and cleaved caspase-1 in neurons. In vivo, SCI model mice were established with a 5 g weight-drop method. MCC950 was intraperitoneally injected at 0, 2, 4, 6, 8, 10, and 12 days after SCI. Basso Mouse Scale (BMS) scores and footprint assays were used to assess motor function. Paw withdrawal threshold and tail flick latency were used to assess somatosensory function. H&E, Nissl and TUNEL staining were used to measure histological changes and apoptosis at 3 days after SCI, and scar formation was observed by Masson staining and GFAP immunohistochemical analysis at 28 days after SCI. Results: Immunofluorescence analysis confirmed that MCC950 inhibited OGD-induced activation of the NLRP3 inflammasome in neurons.

scholarly journals Reducing Neuron Apoptosis in the Pontine Micturition Center by Nerve Root Transfer for Restoration of Micturition Function after Spinal Cord Injury

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Ronghua Yu ◽  
Gang Yin ◽  
Jianguo Zhao ◽  
Huihao Chen ◽  
Depeng Meng ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Nerve Root ◽  
Neuronal Apoptosis ◽  
Nerve Transfer ◽  
Tunel Staining ◽  
Nerve Roots ◽  
Cord Injury ◽  
Group A ◽  
Group B

Objective. The rate of neuronal apoptosis increases after spinal cord injury (SCI). Anastomosing the normal nerve roots above the SCI level to the injured sacral nerve roots can enhance the functional recovery of neurons. Therefore, we evaluated the effect of sacral nerve root transfer after SCI on pontine neuronal survival. Methods. Sprague–Dawley rats were randomly divided into three groups: Group A, reconstruction of afferent and efferent nerve pathways of the bladder after SCI; Group B, SCI only; and Group C, control group. We examined pontine neuronal morphology using hematoxylin and eosin (H&E) staining after SCI and nerve transfer. Bcl-2 and Bax protein expression changes in the pontine micturition center were quantified by immunohistochemistry. The number of apoptotic neurons was determined by TUNEL staining. We examined pontine neuronal apoptosis by transmission electron microscopy (TEM) at different time points. Results. H&E staining demonstrated that the number of neurons had increased in Group A, but more cells in Group B displayed nuclear pyknosis, with the disappearance of the nucleus. Compared with Group B, Group A had significantly higher Bcl-2 expression, significantly lower Bax expression, and a significantly higher Bcl-2/Bax ratio. The number of apoptotic neurons and neuron bodies in Group A was significantly lower than that in Group B, as indicated by TUNEL staining and TEM. Conclusions. These findings demonstrate that lumbosacral nerve transfer can reduce neuronal apoptosis in the pontine micturition center and enhance functional recovery of neurons. This result further suggests that lumbosacral nerve transfer can be used as a new approach for reconstructing bladder function after spinal cord injury.

scholarly journals Local Delivery of β-Elemene Improves Locomotor Functional Recovery by Alleviating Endoplasmic Reticulum Stress and Reducing Neuronal Apoptosis in Rats with Spinal Cord Injury

2018 ◽  
Vol 49 (2) ◽  
pp. 595-609 ◽  
Author(s):  
Jingyu Wang ◽  
Heyangzi Li ◽  
Yucheng Ren ◽  
Ying Yao ◽  
Jue Hu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Ventral Horn ◽  
Tunel Staining ◽  
Cord Injury

Background/Aims: Spinal cord injury (SCI) is a serious global problem that leads to permanent motor and sensory deficits. This study explores the anti-apoptotic and neuroprotective effects of the natural extract β-elemene in vitro and in a rat model of SCI. Methods: CCK-8 assay was used to evaluate cell viability and lactate dehydrogenase assay was used to evaluate cytotoxicity. A model of cell injury was established using cobalt chloride. Apoptosis was evaluated using a fluorescence-activated cell sorting assay of annexin V-FITC and propidium iodide staining. A rat SCI model was created via the modified Allen’s method and Basso, Beattie, and Bresnahan (BBB) scores were used to assess locomotor function. Inflammatory responses were assessed via enzyme-linked immunosorbent assay (ELISA). Apoptotic and surviving neurons in the ventral horn were respectively observed via terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining and Nissl staining. Western blotting was used to measure protein expression. Results: β-elemene (20 μg/ml) promoted cell viability by activating phosphorylation of the PI3K-AKT-mTOR pathway. β-elemene reduced CoCl2-induced cellular death and apoptosis by suppressing the expression levels of CHOP, cleaved-caspase 12, 78-kilodalton glucose-regulated protein, cleaved-caspase 3, and the Bax/Bcl-2 ratio. In the rat model of SCI, Nissl and TUNEL staining showed that β-elemene promoted motor neuron survival and reduced neuronal apoptosis in the spinal cord ventral horn. BBB scores showed that β-elemene significantly promoted locomotor behavioral recovery after SCI. In addition, β-elemene reduced the ELISA-detected secretion of interleukin (IL)-6 and IL-1β. Conclusion: β-elemene reduces neuronal apoptosis by alleviating endoplasmic reticulum stress in vitro and in vivo. In addition, β-elemene promotes locomotor function recovery and tissue repair in SCI rats. Thus, our study provides a novel encouraging strategy for the potential treatment of β-elemene in SCI patients.

Drastic Decrease in Isoflurane Minimum Alveolar Concentration and Limb Movement Forces after Thoracic Spinal Cooling and Chronic Spinal Transection in Rats

2005 ◽  
Vol 102 (3) ◽  
pp. 624-632 ◽  
Author(s):  
Steven L. Jinks ◽  
Carmen L. Dominguez ◽  
Joseph F. Antognini
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Minimum Alveolar Concentration ◽  
Tail Flick ◽  
Noxious Stimulation ◽  
Partial Recovery ◽  
Spinal Transection ◽  
Thoracic Spinal ◽  
Cord Injury ◽  
Stimulation Of

Background Individuals with spinal cord injury may undergo multiple surgical procedures; however, it is not clear how spinal cord injury affects anesthetic requirements and movement force under anesthesia during both acute and chronic stages of the injury. Methods The authors determined the isoflurane minimum alveolar concentration (MAC) necessary to block movement in response to supramaximal noxious stimulation, as well as tail-flick and hind paw withdrawal latencies, before and up to 28 days after thoracic spinal transection. Tail-flick and hind paw withdrawal latencies were measured in the awake state to test for the presence of spinal shock or hyperreflexia. The authors measured limb forces elicited by noxious mechanical stimulation of a paw or the tail at 28 days after transection. Limb force experiments were also conducted in other animals that received a reversible spinal conduction block by cooling the spinal cord at the level of the eighth thoracic vertebra. Results A large decrease in MAC (to </= 40% of pretransection values) occurred after spinal transection, with partial recovery (to approximately 60% of control) at 14-28 days after transection. Awake tail-flick and hind paw withdrawal latencies were facilitated or unchanged, whereas reflex latencies under isoflurane were depressed or absent. However, at 80-90% of MAC, noxious stimulation of the hind paw elicited ipsilateral limb withdrawals in all animals. Hind limb forces were reduced (by >/= 90%) in both chronic and acute cold-block spinal animals. Conclusions The immobilizing potency of isoflurane increases substantially after spinal transection, despite the absence of a baseline motor depression, or "spinal shock." Therefore, isoflurane MAC is determined by a spinal depressant action, possibly counteracted by a supraspinal facilitatory action. The partial recovery in MAC at later time points suggests that neuronal plasticity after spinal cord injury influences anesthetic requirements.

Neuronal Apoptosis Is Inhibited by Cord Blood Stem Cells after Spinal Cord Injury

2009 ◽  
Vol 26 (11) ◽  
pp. 2057-2069 ◽  
Author(s):  
Venkata Ramesh Dasari ◽  
Krishna Kumar Veeravalli ◽  
Andrew J. Tsung ◽  
Christopher S. Gondi ◽  
Meena Gujrati ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Cord Blood ◽  
Neuronal Apoptosis ◽  
Cord Injury ◽  
Blood Stem Cells ◽  
Cord Blood Stem Cells

Up-regulation of TRAF2 Suppresses Neuronal Apoptosis after Rat Spinal Cord Injury

2017 ◽  
Vol 49 (5) ◽  
pp. 589-596 ◽  
Author(s):  
Guanhua Xu ◽  
Jinlong Zhang ◽  
Lingling Wang ◽  
Zhiming Cui ◽  
Xu Sun ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Apoptosis ◽  
Rat Spinal Cord ◽  
Cord Injury

scholarly journals LOTUS Inhibits Neuronal Apoptosis and Promotes Tract Regeneration in Contusive Spinal Cord Injury Model Mice

eNeuro ◽  
2018 ◽  
Vol 5 (5) ◽  
pp. ENEURO.0303-18.2018 ◽  
Author(s):  
Shuhei Ito ◽  
Narihito Nagoshi ◽  
Osahiko Tsuji ◽  
Shinsuke Shibata ◽  
Munehisa Shinozaki ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neuronal Apoptosis ◽  
Spinal Cord Injury Model ◽  
Injury Model ◽  
Cord Injury ◽  
Contusive Spinal Cord Injury

scholarly journals Small extracellular vesicles encapsulating CCL2 from activated astrocytes induce microglial activation and neuronal apoptosis after traumatic spinal cord injury

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Yuluo Rong ◽  
Chengyue Ji ◽  
Zhuanghui Wang ◽  
Xuhui Ge ◽  
Jiaxing Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Extracellular Vesicles ◽  
Neuronal Apoptosis ◽  
Microglial Activation ◽  
Neuronal Cells ◽  
Cell Communication ◽  
Bioactive Lipids ◽  
Cord Injury

Abstract Background Spinal cord injury (SCI) is a severe traumatic disease which causes high disability and mortality rates. The molecular pathological features after spinal cord injury mainly involve the inflammatory response, microglial and neuronal apoptosis, abnormal proliferation of astrocytes, and the formation of glial scars. However, the microenvironmental changes after spinal cord injury are complex, and the interactions between glial cells and nerve cells remain unclear. Small extracellular vesicles (sEVs) may play a key role in cell communication by transporting RNA, proteins, and bioactive lipids between cells. Few studies have examined the intercellular communication of astrocytes through sEVs after SCI. The inflammatory signal released from astrocytes is known to initiate microglial activation, but its effects on neurons after SCI remain to be further clarified. Methods Electron microscopy (TEM), nanoparticle tracking analysis (NTA), and western blotting were applied to characterize sEVs. We examined microglial activation and neuronal apoptosis mediated by astrocyte activation in an experimental model of acute spinal cord injury and in cell culture in vitro. Results Our results indicated that astrocytes activated after spinal cord injury release CCL2, act on microglia and neuronal cells through the sEV pathway, and promote neuronal apoptosis and microglial activation after binding the CCR2. Subsequently, the activated microglia release IL-1β, which acts on neuronal cells, thereby further aggravating their apoptosis. Conclusion This study elucidates that astrocytes interact with microglia and neurons through the sEV pathway after SCI, enriching the mechanism of CCL2 in neuroinflammation and spinal neurodegeneration, and providing a new theoretical basis of CCL2 as a therapeutic target for SCI.

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