The effect of glutamine on locomotor performance and skeletal muscle myosins following spinal cord injury in rats

2006 ◽  
Vol 101 (4) ◽  
pp. 1045-1052 ◽  
Author(s):  
Jamie D. Golding ◽  
Sarah T. Rigley MacDonald ◽  
Bernhard H. J. Juurlink ◽  
Benjamin W. C. Rosser
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Extensor Digitorum Longus ◽  
Critical Role ◽  
Extensor Digitorum ◽  
Secondary Injury ◽  
Significant Difference ◽  
Cord Injury ◽  
Functional Scores

Following initial spinal cord injury (SCI), a cascade of pathological events, including oxidative stress, leads to secondary injury. Glutathione (GSH) plays a critical role in oxidant scavenging. Maintenance of GSH concentrations after SCI lessens secondary injury and improves recovery. Since glutamine promotes GSH synthesis, this nonessential amino acid was examined for therapeutic potential. Denervation alters the expression of myosin heavy chain (MHC) isoforms within skeletal muscles. The hypotheses of this study were that glutamine administration to SCI rats would lead to improved functional recovery and more preserved MHC phenotypes in representative locomotor muscles. Male Wistar rats were divided into four groups: healthy, sham with laminectomy, laminectomized SCI untreated, and laminectomized SCI treated with glutamine. Functional performance was measured weekly for 6 wk using Basso-Beattie-Bresnahan scale and angle board methods. MHC composition of rat soleus and extensor digitorum longus muscles was determined using SDS-PAGE. Glutamine-treated rats had significantly higher angle board scores ( P < 0.001) and Basso-Beattie-Bresnahan scores ( P < 0.01) than untreated SCI rats. Soleus of healthy rats contained 94% type 1 myosin isoform. Treated rats maintained 68%, which was significantly ( P < 0.001) greater than 28% in untreated rats. The extensor digitorum longus of healthy rats contained 55% type 2b myosin. There was a significant ( P < 0.001) decrease in this isoform following SCI, but no significant difference between treated and untreated groups. There were strong correlations between higher functional scores and more preserved MHC phenotypes. Our findings suggest glutamine improves functional recovery and helps preserve myosin profile by reducing secondary SCI, thereby maintaining more nerves.

scholarly journals IL-1β-induces NF-κB and upregulates microRNA-372 to inhibit spinal cord injury recovery

2017 ◽  
Vol 117 (6) ◽  
pp. 2282-2291 ◽  
Author(s):  
Wei Zhou ◽  
Tongzhou Yuan ◽  
Youshui Gao ◽  
Peipei Yin ◽  
Wei Liu ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Functional Recovery ◽  
Neuronal Damage ◽  
Critical Role ◽  
Myeloperoxidase Activity ◽  
Cell Transplant ◽  
Tissue Water ◽  
Cord Injury

Excessive inflammation including IL-1β-initiated signaling is among the earlies reactions that can cause neuronal damage following spinal cord injury (SCI). It has been suggested that microRNAs may participate in stem cell repair to facilitate functional recovery following SCI. In this study we have shown that in cultured human neural stem cells (hNSC), IL-1β reduced the expression of both KIF3B (kinesin family member 3B) and NOSIP (nitric oxide synthase-interacting protein), two key modulators for restricting inflammation and promoting neuronal regeneration. The induction of microRNA-372 (miR-372) by IL-1β is specifically responsible for the inhibition of KIF3B and NOSIP. The 3′-untranslated regions (UTRs) of both KIF3B and NOSIP contain targeting sequences to miR-372 that directly inhibit their expression. Moreover, we found that the expression of miR-372 was stimulated in hNSC by IL-1β through an NF-κB binding site at its promoter region. Finally, stable overexpression of miR-372 inhibitor in hNSC rescued the IL-1β-induced impairment as shown by significant improvements in tissue water content, myeloperoxidase activity, and behavioral assessments in SCI rats. These findings suggest a critical role of miR-372 in inflammatory signaling and pinpoint a novel target for the treatment of acute SCI. NEW & NOTEWORTHY Our data demonstrate that IL-1β can impair the functional recovery of neural stem cell transplant therapy for spinal cord injury (SCI) treatment in rats. This effect is dependent on microRNA-372 (miR-372)-dependent gene repression of KIF3B and NOSIP. Therefore, specific knockdown of miR-372 may provide benefits for SCI treatments.

Interleukin-33 treatment reduces secondary injury and improves functional recovery after contusion spinal cord injury

2015 ◽  
Vol 44 ◽  
pp. 68-81 ◽  
Author(s):  
Yuriy Pomeshchik ◽  
Iurii Kidin ◽  
Paula Korhonen ◽  
Ekaterina Savchenko ◽  
Merja Jaronen ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Secondary Injury ◽  
Interleukin 33 ◽  
Cord Injury

scholarly journals Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel J. Hellenbrand ◽  
Charles M. Quinn ◽  
Zachariah J. Piper ◽  
Carolyn N. Morehouse ◽  
Jordyn A. Fixel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Immune Cell ◽  
Sensory Function ◽  
Glutamate Excitotoxicity ◽  
Secondary Injury ◽  
Extensive Literature ◽  
Secondary Damage ◽  
Cord Injury

AbstractTraumatic spinal cord injury (SCI) is a devastating neurological condition that results in a loss of motor and sensory function. Although extensive research to develop treatments for SCI has been performed, to date, none of these treatments have produced a meaningful amount of functional recovery after injury. The primary injury is caused by the initial trauma to the spinal cord and results in ischemia, oxidative damage, edema, and glutamate excitotoxicity. This process initiates a secondary injury cascade, which starts just a few hours post-injury and may continue for more than 6 months, leading to additional cell death and spinal cord damage. Inflammation after SCI is complex and driven by a diverse set of cells and signaling molecules. In this review, we utilize an extensive literature survey to develop the timeline of local immune cell and cytokine behavior after SCI in rodent models. We discuss the precise functional roles of several key cytokines and their effects on a variety of cell types involved in the secondary injury cascade. Furthermore, variations in the inflammatory response between rats and mice are highlighted. Since current SCI treatment options do not successfully initiate functional recovery or axonal regeneration, identifying the specific mechanisms attributed to secondary injury is critical. With a more thorough understanding of the complex SCI pathophysiology, effective therapeutic targets with realistic timelines for intervention may be established to successfully attenuate secondary damage.

Effects of FABP7 on functional recovery after spinal cord injury in adult mice

2019 ◽  
Vol 31 (2) ◽  
pp. 291-297 ◽  
Author(s):  
Nobuo Senbokuya ◽  
Hideyuki Yoshioka ◽  
Takashi Yagi ◽  
Yuji Owada ◽  
Hiroyuki Kinouchi
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Functional Recovery ◽  
Gene Knockout ◽  
Neuronal Injury ◽  
Wild Type ◽  
Fatty Acid Binding ◽  
Significant Difference ◽  
Cord Injury ◽  
In The Wild

OBJECTIVEElucidating the mechanisms of neuronal injury is crucial for the development of spinal cord injury (SCI) treatments. Brain-type fatty acid–binding protein 7 (FABP7) is expressed in the adult rodent brain, especially in astrocytes, and has been reported to play a role in astrocyte function in various types of brain damage; however, its role after SCI has not been well studied. In this study, the authors evaluated the expression change of FABP7 after SCI using a mouse spinal cord compression model and observed the effect of FABP7 gene knockout on neuronal damage and functional recovery after SCI.METHODSFemale FABP7 knockout (KO) mice with a C57BL/6 background and their respective wild-type littermates were subjected to SCI with a vascular clip. The expression of FABP7, neuronal injury, and functional recovery after SCI were analyzed in both groups of mice.RESULTSWestern blot analysis revealed upregulation of FABP7 in the wild-type mice, which reached its peak 14 days after SCI, with a significant difference in comparison to the control mice. Immunohistochemistry also showed upregulation of FABP7 at the same time points, mainly in proliferative astrocytes. The number of surviving ventral neurons in the FABP7-KO mice at 28 days after SCI was significantly lower than that observed in the wild-type mice. In addition, motor functional recovery in the FABP7-KO mice was significantly worse than that of the wild-type mice.CONCLUSIONSThe findings of this study indicate that FABP7 could have a neuroprotective role that might be associated with modulation of astrocytes after SCI. FABP7 could potentially be a therapeutic target in the treatment of SCI.

scholarly journals Inhibiting microglia proliferation after spinal cord injury improves recovery in mice and nonhuman primates

2021 ◽  
Author(s):  
Gaëtan Poulen ◽  
Emilie Aloy ◽  
Claire M. Bringuier ◽  
Nadine Mestre-Francés ◽  
Emaëlle V.F. Artus ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Motor Function ◽  
Functional Recovery ◽  
Nonhuman Primates ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Post Injury ◽  
Function Recovery ◽  
Cord Injury

AbstractNo curative treatment is available for any deficits induced by spinal cord injury (SCI). Following injury, microglia undergo highly diverse activation processes, including proliferation, and play a critical role on functional recovery.In a translational objective, we investigated whether a transient pharmacological reduction of microglia proliferation after injury is beneficial for functional recovery after SCI in mice and nonhuman primates. The colony stimulating factor-1 receptor (CSF1R) regulates proliferation, differentiation, and survival of microglia, we thus used an oral administration of GW2580, a CSF1R inhibitor.First, transient post-injury GW2580 administration in mice improves motor function recovery, promotes tissues preservation and/or reorganization (identified by coherent anti-stokes Raman scattering microscopy), and modulates glial reactivity.Second, post-injury GW2580-treatment in nonhuman primates reduces microglia proliferation, improves functional motor function recovery, and promotes tissue protection. Notably, three months after lesion microglia reactivity returned to baseline value.Finally, to initiate the investigation on molecular mechanisms induced by a transient post-SCI GW2580-treatment, we used microglia-specific transcriptomic analysis in mice. Notably, we detected a downregulation in the expression of inflammatory-associated genes and we identified genes that were up-regulated by SCI and further downregulated by the treatment.Thus, a transient oral GW2580 treatment post-injury may provide a promising therapeutic strategy for SCI patients and may also be extended to other central nervous system disorders displaying microglia activation.

Sign in / Sign up

Export Citation Format

Share Document