scholarly journals Minocycline Enhance Restorative Ability of Olfactory Ensheathing Cells by Upregulation of BDNF and GDNF Expression After Spinal Cord Injury

2021 ◽  
Author(s):  
Soheila Pourkhodadad ◽  
◽  
Shahrbanoo Oryan ◽  
Mohammadmehdi Hadipour ◽  
Gholamreza Kaka ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Neurotrophic Factor ◽  
Axon Growth ◽  
Female Rats ◽  
Olfactory Ensheathing Cells ◽  
Injury Site ◽  
Locomotor Function ◽  
Cord Injury ◽  
Ensheathing Cells

Purpose: Spinal cord injury is a global public health issue that results in extensive neuronal degeneration, axonal and myelin loss and severe functional deficits. Neurotrophic factors are potential treatment for reducing secondary damage, promoting axon growth, and are responsible for inducing myelination after injury. Olfactory ensheathing cells (OECs) and minocycline have been shown to promote locomotor function after spinal cord injury. In the present study, we investigated the neuroprotective effects of combined treatment with minocycline and OECs on the spinal cord injury in relation with brain-derived neurotrophic factor (BDNF) and glial derived neurotrophic factor (GDNF) expressions after SCI. Methods: Adult female rats were used to experimental SCI by weight compression method. Rats received intraperitoneal injection of minocycline (90 mg/kg) immediately after SCI and then 24 h after injury. OECs were transplanted one week after the injury. The hindlimb function was assessed using Basso Beattie Bresnahan (BBB) locomotor rating scale and electromyography (EMG). After five weeks, the segment of the spinal cord centered at the injury site was removed for histopathological analysis. Immunohistological and western blot assays were performed to observe the expression of NeuN, BDNF, GDNF and myelin basic protein (MBP). Results: SCI induced loss of locomotor function with decreased BDNF and GDNF expressions in the injury site. Minocycline +OECs increased the score of BBB locomotor scale and increased spared tissue in the injury site. Immunohistochemical results showed NeuN expression significantly increased in minocycline + OECs group than other groups. Also electromyography amplitude in treated rats was increased compared to control group. BDNF, GDNF and MBP expressions and the number of ventral motor neurons increased further by minocycline + OECs in SCI rats. Conclusion: The present study provides the evidence that minocycline may facilitate recovery of locomotor function by OECs through increasing of BDNF and GDNF expressions following SCI.

Inhibition of x-irradiation–enhanced locomotor recovery after spinal cord injury by hyperbaric oxygen or the antioxidant nitroxide tempol

2007 ◽  
Vol 6 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Virany H. Hillard ◽  
Hong Peng ◽  
Kaushik Das ◽  
Raj Murali ◽  
Chitti R. Moorthy ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Hyperbaric Oxygen ◽  
Spinal Cord Tissue ◽  
Irradiation Site ◽  
Injury Site ◽  
Locomotor Recovery ◽  
Locomotor Function ◽  
Cord Injury ◽  
X Irradiation

Object Hyperbaric oxygen (HBO), the nitroxide antioxidant tempol, and x-irradiation have been used to promote locomotor recovery in experimental models of spinal cord injury. The authors used x-irradiation of the injury site together with either HBO or tempol to determine whether combined therapy offers greater benefit to rats. Methods Contusion injury was produced with a weight-drop device in rats at the T-10 level, and recovery was determined using the 21-point Basso-Beattie-Bresnahan (BBB) locomotor scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater after x-irradiation (20 Gy) of the injury site or treatment with tempol (275 mg/kg intraperitoneally) than in untreated rats (final BBB Scores 10.6 [x-irradiation treated] and 9.1 [tempol treated] compared with 6.4 [untreated], p < 0.05). Recovery was not significantly improved by HBO (2 atm for 1 hour [BBB Score 8.2, p > 0.05]). Interestingly, the improved recovery of locomotor function after x-irradiation, in contrast with antiproliferative radiotherapy for neoplasia, was inhibited when used together with either HBO or tempol (BBB Scores 8.2 and 8.3, respectively). The ability of tempol to block enhanced locomotor recovery by x-irradiation was accompanied by prevention of alopecia at the irradiation site. The extent of locomotor recovery following treatment with tempol, HBO, and x-irradiation correlated with measurements of spared spinal cord tissue at the contusion epicenter. Conclusions These results suggest that these treatments, when used alone, can activate neuroprotective mechanisms but, in combination, may result in neurotoxicity.

scholarly journals Comparison of intramedullary transplantation of olfactory ensheathing cell for patients with chronic complete spinal cord injury worldwide

2018 ◽  
Vol 1 (1) ◽  
pp. 146-151 ◽  
Author(s):  
Lin Chen ◽  
Yuqi Zhang ◽  
Xijing He ◽  
Saberi Hooshang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Transplantation ◽  
Clinical Results ◽  
Postoperative Management ◽  
Olfactory Ensheathing Cells ◽  
Olfactory Ensheathing Cell ◽  
Advantages And Disadvantages ◽  
Cord Injury ◽  
Ensheathing Cells

Objectives:Traumatic spinal cord injury (tSCI) remains a major clinical challenge. Cell transplantation brings a glimmer of light, among them olfactory ensheathing cells (OECs) have shown some neurorestorative effect. Due to the results of each group lack basic consistency, many technical details are believed to affect the overall outcome. We compare the clinical outcome of intramedullary transplant of olfactory ensheathing cells for patients with spinal cord injury at multi-centers worldwide, and to explore the potential standardized transplantation that suits for the clinical requirements.Methods:Here, we used the Pubmed and CNKI databases to search online the literatures published in the last 20 years for the clinical studies/trials of OECs for chronic spinal cord injury in the representative clinical center. The results of these representative clinical treatment centers were searched and analyzed. The parameters which may affect the effect including the concentration of cells, the total number of cells, the choice of incision, the site of transplantation, the number of transplantation sites, the advantages and disadvantages of transplantation equipment, and postoperative management, were compared carefully to clarify its impact on the clinical results.Results:In these literatures, 2 Chinese centers, 1 Australian center and 1 European center were selected for intraspinal transplantation. The reason of different results may be due to the excessive injection times and/or the excessive total injection volume.Conclusions:Cell implant to the spinal cord parenchyma is effective for restoring neurological functions, but improper procedures may lead to ineffective results. Concise surgery appears to be more suitable for clinical application than ostensibly precise and complex injection procedures. Sufficient rehabilitation training is surely necessary for the integration of motor recovery after cell transplantation.

Survival, Integration, and Axon Growth Support of Glia Transplanted into the Chronically Contused Spinal Cord

2005 ◽  
Vol 14 (4) ◽  
pp. 225-240 ◽  
Author(s):  
D. J. Barakat ◽  
S. M. Gaglani ◽  
S. R. Neravetla ◽  
A. R. Sanchez ◽  
C. M. Andrade ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Fluorescent Protein ◽  
Three Dimensional ◽  
Axon Growth ◽  
Experimental Models ◽  
Chronic Injury ◽  
Injury Site ◽  
Position Errors ◽  
Cord Injury

Due to an ever-growing population of individuals with chronic spinal cord injury, there is a need for experimental models to translate efficacious regenerative and reparative acute therapies to chronic injury application. The present study assessed the ability of fluid grafts of either Schwann cells (SCs) or olfactory ensheathing glia (OEG) to facilitate the growth of supraspinal and afferent axons and promote restitution of hind limb function after transplantation into a 2-month-old, moderate, thoracic (T8) contusion in the rat. The use of cultured glial cells, transduced with lentiviral vectors encoding enhanced green fluorescent protein (EGFP), permitted long-term tracking of the cells following spinal cord transplantation to examine their survival, migration, and axonal association. At 3 months following grafting of 2 million SCs or OEG in 6 μl of DMEM/F12 medium into the injury site, stereological quantification of the three-dimensional reconstructed spinal cords revealed that an average of 17.1 ± 6.8% of the SCs and 2.3 ± 1.4% of the OEG survived from the number transplanted. In the OEG grafted spinal cord, a limited number of glia were unable to prevent central cavitation and were found in patches around the cavity rim. The transplanted SCs, however, formed a substantive graft within the injury site capable of supporting the ingrowth of numerous, densely packed neurofilament-positive axons. The SC grafts were able to support growth of both ascending calcitonin gene-related peptide (CGRP)-positive and supraspinal serotonergic axons and, although no biotinylated dextran amine (BDA)-traced corticospinal axons were present within the center of the grafts, the SC transplants significantly increased corticospinal axon numbers immediately rostral to the injury–graft site compared with injury-only controls. Moreover, SC grafted animals demonstrated modest, though significant, improvements in open field locomotion and exhibited less foot position errors (base of support and foot rotation). Whereas these results demonstrate that SC grafts survive, support axon growth, and can improve functional outcome after chronic contusive spinal cord injury, further development of OEG grafting procedures in this model and putative combination strategies with SC grafts need to be further explored to produce substantial improvements in axon growth and function.

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