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.

scholarly journals Connexin43 Mimetic Peptides Reduce Swelling, Astrogliosis, and Neuronal Cell Death after Spinal Cord Injury

2008 ◽  
Vol 15 (1-2) ◽  
pp. 27-42 ◽  
Author(s):  
Simon J. O'Carroll ◽  
Mamoun Alkadhi ◽  
Louise F. B. Nicholson ◽  
Colin R. Green
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cord Injury ◽  
Mimetic Peptides

scholarly journals Disrupted autophagy after spinal cord injury is associated with ER stress and neuronal cell death

2015 ◽  
Vol 6 (1) ◽  
pp. e1582-e1582 ◽  
Author(s):  
S Liu ◽  
C Sarkar ◽  
M Dinizo ◽  
A I Faden ◽  
E Y Koh ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Er Stress ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cord Injury

scholarly journals Calpain Inhibitors Prevent Neuronal Cell Death and Ameliorate Motor Disturbances after Compression-Induced Spinal Cord Injury in Rats

2005 ◽  
Vol 22 (3) ◽  
pp. 398-406 ◽  
Author(s):  
Shinya Arataki ◽  
Kazuhito Tomizawa ◽  
Akiyoshi Moriwaki ◽  
Keiichirou Nishida ◽  
Masayuki Matsushita ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Cord Injury ◽  
Calpain Inhibitors ◽  
Motor Disturbances

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 Red-light (670 nm) therapy reduces mechanical sensitivity and neuronal cell death, and alters glial responses following spinal cord injury in rats

2020 ◽  
Author(s):  
Di Hu ◽  
Gila Moalem-Taylor ◽  
Jason R Potas
Keyword(s):  
Spinal Cord ◽  
Cell Death ◽  
Neuronal Cell Death ◽  
Red Light ◽  
Neuronal Cell ◽  
Light Treatment ◽  
Mechanical Sensitivity ◽  
Post Injury ◽  
Mechanical Hypersensitivity ◽  
Cord Injury

AbstractIndividuals with spinal cord injury (SCI) often develop debilitating neuropathic pain, which may be driven by neuronal damage and neuroinflammation. We have previously demonstrated that treatment using 670 nm (red) light irradiation alters microglia/macrophage responses and alleviates mechanical hypersensitivity at 7-days post-injury. Here, we investigated the effect of red-light on the development of mechanical hypersensitivity, neuronal markers, and glial response in the subacute stage (days 1-7) following SCI. Wistar rats were subjected to a mild T10 hemi-contusion SCI or sham surgery followed by daily red-light treatment (30 min/day; 670 nm LED; 35mW/cm2) or sham treatment. Mechanical sensitivity of the rat dorsum was assessed from 1-day post-injury and repeated every second day. Spinal cords were collected at 1, 3, 5 and 7-days post-injury for analysis of myelination, neurofilament protein NF200 expression, neuronal cell death, reactive astrocytes (GFAP+ cells), interleukin1β (IL1β) expression, and inducible nitric oxide synthase (iNOS) production in IBA1+ microglia/macrophages. Red-light treatment significantly reduced the cumulative mechanical sensitivity and the hypersensitivity incidence following SCI. This effect was accompanied by significantly reduced neuronal cell death, reduced astrocyte activation and reduced iNOS expression in IBA1+ cells at the level of the injury. However, myelin and NF200 immunoreactivity and IL1β expression in GFAP+ and IBA1+ cells were not altered by red-light treatment. Thus, red-light therapy may represent a useful non-pharmacological approach for treating pain during the subacute period after SCI by decreasing neuronal loss and modulating the inflammatory glial response.

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