Gene expression profiling of acute spinal cord injury reveals spreading inflammatory signals and neuron loss

We have completed the first large-scale gene expression study of acute spinal cord injury (SCI) in rat. Oligonucleotide microarrays containing 1,200 gene-specific probes were used to quantify mRNA levels, relative to uninjured controls, in spinal cords injured using a standard contusion model. Our results revealed a marked loss of neuron-specific mRNAs at the injury site. The surviving cells showed a characteristic inflammatory response that started at the injury site and spread to the distal cord. Changes in several mRNA levels were associated with putative regenerative responses in the spinal cord. Notably, phosphodiesterase 4, nestin, glia-derived neurite promoting factor, and GAP-43 mRNAs increased significantly. Other mRNAs clustered temporally and spatially with these regeneration-associated genes. Thus we have described global patterns of gene expression following acute SCI, and we have identified targets for future study and possible therapeutic intervention.

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Poster 255 Microarray study of gene expression profile after acute spinal cord injury Leslie R. Morse DO (Boston Med Ctr, Boston, MA); Ricardo A. Battaglino PhD; Martha Joe; David Meguerdichian; Hajime Sasaki DDS, PhD; Steve Williams MD, [email protected]

Archives of Physical Medicine and Rehabilitation ◽

10.1016/j.apmr.2004.07.322 ◽

2004 ◽

Vol 85 (9) ◽

pp. e51

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Gene Expression Profile ◽

Expression Profile ◽

Acute Spinal Cord Injury ◽

Microarray Study ◽

Cord Injury

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Influence of Different ECM-Like Hydrogels on Neurite Outgrowth Induced by Adipose Tissue-Derived Stem Cells

Stem Cells International ◽

10.1155/2017/6319129 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 6

Author(s):

E. Oliveira ◽

R. C. Assunção-Silva ◽

O. Ziv-Polat ◽

E. D. Gomes ◽

F. G. Teixeira ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Growth Factors ◽

Axonal Outgrowth ◽

Mrna Levels ◽

Cord Injury

Mesenchymal stem cells (MSCs) have been proposed for spinal cord injury (SCI) applications due to their capacity to secrete growth factors and vesicles—secretome—that impacts important phenomena in SCI regeneration. To improve MSC survival into SCI sites, hydrogels have been used as transplantation vehicles. Herein, we hypothesized if different hydrogels could interact differently with adipose tissue-derived MSCs (ASCs). The efficacy of three natural hydrogels, gellan gum (functionalized with a fibronectin peptide), collagen, and a hydrogel rich in laminin epitopes (NVR-gel) in promoting neuritogenesis (alone and cocultured with ASCs), was evaluated in the present study. Their impact on ASC survival, metabolic activity, and gene expression was also evaluated. Our results indicated that all hydrogels supported ASC survival and viability, being this more evident for the functionalized GG hydrogels. Moreover, the presence of different ECM-derived biological cues within the hydrogels appears to differently affect the mRNA levels of growth factors involved in neuronal survival, differentiation, and axonal outgrowth. All the hydrogel-based systems supported axonal growth mediated by ASCs, but this effect was more robust in functionalized GG. The data herein presented highlights the importance of biological cues within hydrogel-based biomaterials as possible modulators of ASC secretome and its effects for SCI applications.

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Intravenous Infusion of Mesenchymal Stem Cells Alters Motor Cortex Gene Expression in a Rat Model of Acute Spinal Cord Injury

Journal of Neurotrauma ◽

10.1089/neu.2018.5793 ◽

2019 ◽

Vol 36 (3) ◽

pp. 411-420 ◽

Cited By ~ 4

Author(s):

Tsutomu Oshigiri ◽

Toru Sasaki ◽

Masanori Sasaki ◽

Yuko Kataoka-Sasaki ◽

Masahito Nakazaki ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Motor Cortex ◽

Rat Model ◽

Intravenous Infusion ◽

Acute Spinal Cord Injury ◽

Cord Injury

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Fosl1 Targets AMPK to Inhibit Autophagy-Mediated Anti-Apoptotic and Anti-Inflammatory Effects in Spinal Cord Injury

10.21203/rs.3.rs-105918/v1 ◽

2020 ◽

Author(s):

Lin Zhong ◽

Sheng Fang ◽

An-Quan Wang ◽

Tao Wang ◽

Wei Huang ◽

...

Keyword(s):

Gene Expression ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Animal Model ◽

Inflammatory Factor ◽

Mrna Levels ◽

Ampk Activation ◽

Cord Injury ◽

Anti Inflammatory

Abstract Background: The objective of this study was to delineate the role of Fosl1 in regulating inflammation and apoptosis following spinal cord injury.Methods: GSE45006 datasets from Gene Expression Omnibus (GEO) were explored to analyze Fosl1 gene expression. Next, we established an animal model to assess Fosl1 and AMPK by western blotting, real-time PCR, and immunohistochemical staining and used immunofluorescence staining to check Fosl1 expression in neurons. Fosl1 silencing was used to assess the effect on AMPK, cell viability, autophagy, inflammation and apoptosis. Subsequently, an AMPK activator and inhibitor were added to PC-12 cells with H2O2-induced injury subjected to si-Fosl1 treatment to examine the change in the above indexes and to determine whether the benefits from Fosl1 silencing occurred via AMPK. Moreover, we employed chloroquine (CQ) and rapamycin (RAP) to activate and inhibit autophagy, respectively, and revealed the effects of the upregulation and downregulation of autophagy following AMPK interference. Finally, an animal model was used to identify the effect of si-Fosl1 in vivo.Results: Based on the analysis of the GSE45006 datasets, Fosl1 was found to be highly expressed and was also found to be significantly enhanced in our animal model. Fosl1 knockdown upregulated AMPK at the protein and mRNA levels, promoted autophagic proteins (LC3 II/I, Beclin1) and inhibited inflammatory factors (IL-1β, IL-6, TNF-α) and apoptosis markers (caspase3, Bax). However, Fosl1 decreased the negatively related autophagic protein p62, the anti-inflammatory factor IL-10 and the anti-apoptotic marker Bcl-2. By utilizing compound C (com, an AMPK inhibitor), we learned that AMPK inhibition exhibited unfavorable effects on autophagy but promoted inflammation and apoptosis following Fosl1 silencing. AMPK activation showed contrasting effects. Moreover, we used CQ (an autophagic inhibitor), which indicated that CQ reversed the benefits of AMPK activation on inflammation and apoptosis. The autophagic activator RAP attenuated the negative effects after com treatment. In vivo, si-Fosl1 increased BBB scores at 7 d and 14 d and motor neurons, meanwhile, it decreased the number of apoptotic cells, and inflammatory cytokine expression at 14 d postoperation. Conclusion: Fosl1 can suppress AMPK to promote inflammation and apoptosis through autophagy in SCI.

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A Brief Analysis of Traditional Chinese Medical Elongated Needle Therapy on Acute Spinal Cord Injury and Its Mechanism

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/828754 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Mengxuan Du ◽

Rongliang Chen ◽

Renfu Quan ◽

Liang Zhang ◽

Jinwei Xu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Caspase 3 ◽

Spinal Injury ◽

Therapy Group ◽

Acute Spinal Cord Injury ◽

Mrna Levels ◽

Model Group ◽

Blank Group ◽

Cord Injury

Acute spinal cord injury is one of the most common and complicated diseases among human spinal injury. We aimed to explore the effect of point-through-point acupuncture therapy with elongated needles on acute spinal cord injury in rabbits and its possible mechanism. Adult rabbits were randomly divided into a model group, elongated needle therapy group, and blank group. Immunohistochemical staining showed that the protein levels of Fas and caspase-3 in the model group were significantly higher than those in the blank group at each time point (P<0.05) and significantly lower than those in the elongated needle therapy group on the 3rd and 5th days after operation (P<0.05). RT-PCR showed that Fas and caspase-3 mRNA levels in the model group and elongated needle therapy group were significantly higher than those in the blank group (P<0.05, 0.01). The mRNA levels of Fas and caspase-3 in the elongated needle therapy group were significantly lower than those in model group on the 3rd day (P<0.05, 0.01). Therefore, we confirmed that elongated needle therapy has an obvious effect on acute spinal cord injury in rabbits. Its mechanism is made possible by inhibiting the expression of the Fas→caspase-3 cascade, thereby inhibiting cell apoptosis after spinal cord injury.

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Markedly Deranged Injury Site Metabolism and Impaired Functional Recovery in Acute Spinal Cord Injury Patients With Fever

Critical Care Medicine ◽

10.1097/ccm.0000000000003134 ◽

2018 ◽

Vol 46 (7) ◽

pp. 1150-1157 ◽

Cited By ~ 9

Author(s):

Mathew J. Gallagher ◽

Argyro Zoumprouli ◽

Isaac Phang ◽

Jan M. Schwab ◽

Marcel A. Kopp ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Functional Recovery ◽

Acute Spinal Cord Injury ◽

Injury Site ◽

Cord Injury

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Acute Spinal Cord Injury: Monitoring Lumbar Cerebrospinal Fluid Provides Limited Information about the Injury Site

Journal of Neurotrauma ◽

10.1089/neu.2019.6789 ◽

2020 ◽

Vol 37 (9) ◽

pp. 1156-1164 ◽

Cited By ~ 1

Author(s):

Florence R.A. Hogg ◽

Mathew J. Gallagher ◽

Siobhan Kearney ◽

Argyro Zoumprouli ◽

Marios C. Papadopoulos ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cerebrospinal Fluid ◽

Acute Spinal Cord Injury ◽

Limited Information ◽

Injury Site ◽

Cord Injury ◽

Lumbar Cerebrospinal Fluid

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Differential expression of metabolic genes essential for glucose and lipid metabolism in skeletal muscle from spinal cord injured subjects

Journal of Applied Physiology ◽

10.1152/japplphysiol.00686.2010 ◽

2011 ◽

Vol 110 (5) ◽

pp. 1204-1210 ◽

Cited By ~ 14

Author(s):

Yun Chau Long ◽

Emil Kostovski ◽

Hanneke Boon ◽

Nils Hjeltnes ◽

Anna Krook ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Mrna Levels ◽

Metabolic Gene ◽

Metabolic Gene Expression ◽

Cord Injury ◽

The Impact ◽

Spinal Cord Injured

Skeletal muscle plays an important role in the regulation of energy homeostasis; therefore, the ability of skeletal muscle to adapt and alter metabolic gene expression in response to changes in physiological demands is critical for energy balance. Individuals with cervical spinal cord lesions are characterized by tetraplegia, impaired thermoregulation, and altered skeletal muscle morphology. We characterized skeletal muscle metabolic gene expression patterns, as well as protein content, in these individuals to assess the impact of spinal cord injury on critical determinants of skeletal muscle metabolism. Our results demonstrate that mRNA levels and protein expression of skeletal muscle genes essential for glucose storage are reduced, whereas expression of glycolytic genes is reciprocally increased in individuals with spinal cord injury. Furthermore, expression of genes essential for lipid oxidation is coordinately reduced in spinal cord injured subjects, consistent with a marked reduction of mitochondrial proteins. Thus spinal cord injury resulted in a profound and tightly coordinated change in skeletal muscle metabolic gene expression program that is associated with the aberrant metabolic features of the tissue.

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