scholarly journals Subarachnoid Transplant of the Human Neuronal hNT2.19 Serotonergic Cell Line Attenuates Behavioral Hypersensitivity without Affecting Motor Dysfunction after Severe Contusive Spinal Cord Injury

2011 ◽  
Vol 2011 ◽  
pp. 1-24 ◽  
Author(s):  
Mary J. Eaton ◽  
Eva Widerström-Noga ◽  
Stacey Quintero Wolfe
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Line ◽  
Neuronal Cell ◽  
Thermal Hyperalgesia ◽  
Motor Dysfunction ◽  
Differentiated Cells ◽  
Sensory Effects ◽  
Cord Injury ◽  
Base Of Support

Transplant of cells which make biologic agents that can modulate the sensory and motor responses after spinal cord injury (SCI) would be useful to treat pain and paralysis. To address this need for clinically useful human cells, a unique neuronal cell line that synthesizes and secretes/releases the neurotransmitter serotonin (5HT) was isolated. Hind paw tactile allodynia and thermal hyperalgesia induced by severe contusive SCI were potently reversed after lumbar subarachnoid transplant of differentiated cells, but had no effect on open field motor scores, stride length, foot rotation, base of support, or gridwalk footfall errors associated with the SCI. The sensory effects appeared 1 week after transplant and did not diminish during the 8-week course of the experiment when grafts were placed 2 weeks after SCI. Many grafted cells were still present and synthesizing 5HT at the end of the study. These data suggest that the human neuronal serotonergic hNT2.19 cells can be used as a biologic minipump for receiving SCI-related neuropathic pain, but likely requires intraspinal grafts for motor recovery.

scholarly journals Inhibition of microRNA-711 limits angiopoietin-1 and Akt changes, tissue damage, and motor dysfunction after contusive spinal cord injury in mice

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Boris Sabirzhanov ◽  
Jessica Matyas ◽  
Marina Coll-Miro ◽  
Laina Lijia Yu ◽  
Alan I. Faden ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Motor Dysfunction ◽  
Neurological Dysfunction ◽  
Central Administration ◽  
Cord Injury ◽  
Angiopoietin 1

Abstract Spinal cord injury (SCI) causes neuronal cell death and vascular damage, which contribute to neurological dysfunction. Given that many biochemical changes contribute to such secondary injury, treatment approaches have increasingly focused on combined therapies or use of multi-functional drugs. MicroRNAs (miRs) are small (20–23 nucleotide), non-protein-coding RNAs and can negatively regulate target gene expression at the post-transcriptional level. As individual miRs can potentially modulate expression of multiple relevant proteins after injury, they are attractive candidates as upstream regulators of the secondary SCI progression. In the present study we examined the role of miR-711 modulation after SCI. Levels of miR-711 were increased in injured spinal cord early after SCI, accompanied by rapid downregulation of its target angiopoietin-1 (Ang-1), an endothelial growth factor. Changes of miR-711 were also associated with downregulation of the pro-survival protein Akt (protein kinase B), another target of miR-711, with sequential activation of glycogen synthase kinase 3 and the pro-apoptotic BH3-only molecule PUMA. Central administration of a miR-711 hairpin inhibitor after SCI limited decreases of Ang-1/Akt expression and attenuated apoptotic pathways. Such treatment also reduced neuronal/axonal damage, protected microvasculature and improved motor dysfunction following SCI. In vitro, miR-711 levels were rapidly elevated by neuronal insults, but not by activated microglia and astrocytes. Together, our data suggest that post-traumatic miR-711 elevation contributes to neuronal cell death after SCI, in part by inhibiting Ang-1 and Akt pathways, and may serve as a novel therapeutic target.

Subarachnoid Transplant of a Human Neuronal Cell Line Attenuates Chronic Allodynia and Hyperalgesia After Excitotoxic Spinal Cord Injury in the Rat

2007 ◽  
Vol 8 (1) ◽  
pp. 33-50 ◽  
Author(s):  
Mary J. Eaton ◽  
Stacey Quintero Wolfe ◽  
Miguel Martinez ◽  
Massiel Hernandez ◽  
Cassandra Furst ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Line ◽  
Neuronal Cell ◽  
Neuronal Cell Line ◽  
Human Neuronal Cell ◽  
Cord Injury

Studies of a Human Neuron-Like Cell Line in Stroke and Spinal Cord Injury

2003 ◽  
pp. 345-387
Author(s):  
Paul J. Reier ◽  
John Q. Trojanowski ◽  
Virginia M-Y. Lee ◽  
Margaret J. Velardo
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Line ◽  
Cord Injury ◽  
Human Neuron

Activation of SIRT1 by Hyperbaric  Oxygenation Promotes Recovery of Motor Dysfunction in Spinal Cord Injury Rats

2020 ◽  
Author(s):  
Huiqiang Chen ◽  
Mengyu Yao ◽  
Zhibo Li ◽  
Ranran Xing ◽  
Cheng Zhang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Molecular Mechanisms ◽  
Hyperbaric Oxygenation ◽  
Rating Scale ◽  
Motor Dysfunction ◽  
Sprague Dawley ◽  
Inflammatory Cascade ◽  
Locomotor Function ◽  
Cord Injury

Abstract Background: Emerging evidence demonstrated that hyperbaric oxygenation (HBO) therapy improved the locomotor dysfunction following spinal cord injury (SCI). Sirtuin1(SIRT1) has been characterized as neuroprotection in nerve system. However, whether SIRT1 is involved in alleviation of locomotor function by HBO therapy is unclear. Methods: The Basso, Beattie Bresnahan (BBB) locomotor rating scale was used to evaluate the open-field locomotor function. Western blot, real-time quantitative reverse transcription polymerase chain reaction, SIRT1 activity assay and enzyme-linked immunosorbent assays were performed to explore the molecular mechanisms in adult Sprague-Dawley rats. Results: We found that series HBO therapy significantly improved the locomotor dysfunction and ameliorated the decrease mRNA, protein and activity of spinal cord SIRT1 induced by traumatic SCI injury in rats. In addition, intraperitoneal injection SIRT1 antagonist EX-527 abolished the beneficial effects of series HBO treatment on locomotor deficits and SIRT1 activity loss caused by traumatic SCI injury. However, the rats undergone both series HBO therapy and SIRT1 agonist SRT1720 got the higher BBB score than that undergone series HBO treatment only. Importantly, series HBO treatment following the traumatic SCI injury inhibited the inflammatory cascade and apoptosis-related protein, which was retained by EX-527 and enhanced by SRT1720. Furthermore, EX-527 blocked the enhanced induction of autophagy series with HBO application. Conclusion: These findings demonstrated a new mechanism for series HBO therapy involving activation of SIRT1 and subsequent modulation of inflammatory cascade, apoptosis and autophagy, which contributed to the recovery of motor dysfunction. Key words: HBO, SIRT1, motor dysfunction, inflammation, autophagy, apoptosis

Inflammatory Response and Cell Apoptosis are Inhibited by Indirubin-3′-Oxime via PI3K/Akt Pathway in Rat Model of Spinal Cord Injury ​

2020 ◽  
Author(s):  
Yan Zhu ◽  
Lixue Wu ◽  
Qiuxiang Zhou ◽  
Yueyue Yan ◽  
Jinlong Qu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rat Model ◽  
Serum Levels ◽  
Motor Dysfunction ◽  
Akt Phosphorylation ◽  
Treatment Groups ◽  
Ppar Γ ◽  
Post Surgery ◽  
Cord Injury

Abstract Spinal cord injury (SCI) main cause of motor dysfunction results in loss of feelings partially or completely. The current study investigated indirubin-3′-oxime (IR3O) for treatment of SCI in rat model and evaluated the related mechanism. Rats in model SCI and ID30 groups were subjected to laminectomy at 8th thoracic vertebra level. Vertebral column was secured by clamping T6 and T10 and SCI model was established by dripping a hammer. Treatment groups received 0.25, 0.5, 0.75 and 1.0 mg/kg doses of ID30 daily for 2-weeks post-surgery. Treatment with ID30 effectively improved BBB score in rats with SCI in dose-based manner. Accumulation of water in spinal cord tissues was alleviated significantly on treatment of SCI rats with ID30. ID30 treatment significantly alleviated SCI mediated higher serum levels of TNF-α and cytokines (IL-1β and IL-6) in SCI rats. In ID30 treated SCI rats SOD, CAT and GSH activities were significantly alleviated. The SCI mediated increased cleaved caspase-3 and -9 levels were alleviated by ID30 treatment significantly. Moreover, ID30 treatment suppressed SCI mediated elevation of PGE2, COX‑2 levels and significantly (P<0.05) elevated PPAR-γ expression. The ID30 treatment of SCI rats significantly (P<0.05) elevated PI3K and Akt phosphorylation. Thus, ID30 inhibited edema and improved BBB score in rats with SCI by targeting pro-inflammatory cytokines and oxidative response. Moreover, in SCI rats ID30 treatment down-regulated apoptotic proteins, promoted PPAR-γ activation and elevated PI3K/Akt phosphorylation. Thus, ID30 has potential to be studied further for development of therapeutic strategy for SCI.

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