The Experts below are selected from a list of 237 Experts worldwide ranked by ideXlab platform
Jing Zhang - One of the best experts on this subject based on the ideXlab platform.
-
intravenous injections of human mesenchymal stromal cells modulated the redox state in a rat model of Radiation Myelopathy
Evidence-based Complementary and Alternative Medicine, 2015Co-Authors: Jing Zhang, Lianbing Li, Jiayan Wu, Tao Wang, Jifan Yang, Ke Zheng, Shaolin LiAbstract:The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of Radiation Myelopathy. UC-MSCs were isolated from Wharton’s jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 30 Gy of Radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after-irRadiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of Radiation Myelopathy could significantly improve the antioxidative microenvironment in vivo.
-
vascular endothelial growth factor enhanced the angiogenesis response of human umbilical cord derived mesenchymal stromal cells in a rat model of Radiation Myelopathy
Neurochemical Research, 2015Co-Authors: Jing Zhang, Jianing WangAbstract:The present study was designed to examine a synergistic role for VEGF and human umbilical cord-derived MSCs (UC-MSCs) therapy in a rat model of Radiation Myelopathy. UC-MSCs and VEGF were injected through the tail vein at 90, 97, 104 and 111 days post-irRadiation. Behavioral tests were performed, and histological damage was examined. The microcirculation in the spinal cord was assessed using von Willebrand factor immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in the spinal cord. The UC-MSCs processed with VEGF, including VEGF165-induced UC-MSC (iUC), VEGF and UC-MSCs (VEGF-UC), increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, raised the relative magnitude of spinal cord blood flow compared to UC-MSCs treatment alone. Our data provided the first evidence that vascular endothelial growth factor enhanced the angiogenesis response of human umbilical cord-derived mesenchymal stromal cells in a rat model of Radiation Myelopathy.
-
multiple injections of human umbilical cord derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of Radiation Myelopathy
Journal of Translational Medicine, 2014Co-Authors: Jing Zhang, Ke Zheng, Xiubin Xiao, Lei Wang, Feng Liang, Zailiang Yang, Yanqing Wang, Zhifang Li, Jianing WangAbstract:At present, no effective clinical treatment is available for the late effects of Radiation Myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of Radiation Myelopathy. An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irRadiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord. Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord. Multiple injections of UC-MSCs via the tail vein in a rat model of Radiation Myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
Arjun Sahgal - One of the best experts on this subject based on the ideXlab platform.
-
pathobiology of Radiation Myelopathy and strategies to mitigate injury
Spinal Cord, 2015Co-Authors: C S Wong, Arjun Sahgal, Michael G. FehlingsAbstract:This is a narrative review of the literature. The objectives of this study were to review the current concepts underlying the pathobiology of Radiation-induced spinal cord injury; to discuss potential biologic strategies to mitigate spinal cord injury following Radiation; and to provide an update on the clinical guidelines to prevent injury in the era of image-guided stereotactic body radiotherapy (SBRT). This study was conducted in Toronto, Canada. A MEDLINE search was performed using the following terms: Radiation injury; Radiation Myelopathy; CNS Radiation injury; brain necrosis, Radiation; demyelination, Radiation; blood–brain barrier, Radiation; white matter necrosis; and SBRT. The biologic response of the spinal cord after Radiation is a continuously evolving process. Death of vascular endothelial cells and disruption of the blood–spinal cord barrier leads to a complex injury response, resulting in demyelination and tissue necrosis. At present, there is no evidence that the pathobiology of cord injury after SBRT is different from that after standard fractionation. Although permanent Myelopathy has become a rare complication following conventional fractionated Radiation treatment, cases of Radiation Myelopathy have re-emerged with the increasing role of spine stereotactic body Radiation therapy and reirRadiation. Experimental biologic strategies targeting the injury response pathways hold promise in mitigating this dreaded late effect of Radiation treatment.
-
probabilities of Radiation Myelopathy specific to stereotactic body Radiation therapy to guide safe practice
International Journal of Radiation Oncology Biology Physics, 2013Co-Authors: Arjun Sahgal, Vivian Weinberg, Eric L Chang, Samuel T Chao, Alexander Muacevic, Alessandra Gorgulho, Scott G Soltys, Peter C Gerszten, Lilyana AngelovAbstract:Purpose Dose-volume histogram (DVH) results for 9 cases of post spine stereotactic body Radiation therapy (SBRT) Radiation Myelopathy (RM) are reported and compared with a cohort of 66 spine SBRT patients without RM. Methods and Materials DVH data were centrally analyzed according to the thecal sac point maximum (Pmax) volume, 0.1- to 1-cc volumes in increments of 0.1 cc, and to the 2 cc volume. 2-Gy biologically equivalent doses (nBED) were calculated using an α/β = 2 Gy (units = Gy 2/2 ). For the 2 cohorts, the nBED means and distributions were compared using the t test and Mann-Whitney test, respectively. Significance ( P Results Significant differences in both the means and distributions at the Pmax and up to the 0.8-cc volume were observed. Concordant significance was greatest for the Pmax volume. At the Pmax volume the fit of the logistic regression model, summarized by the area under the curve, was 0.87. A risk of RM of 5% or less was observed when limiting the thecal sac Pmax volume doses to 12.4 Gy in a single fraction, 17.0 Gy in 2 fractions, 20.3 Gy in 3 fractions, 23.0 Gy in 4 fractions, and 25.3 Gy in 5 fractions. Conclusion We report the first logistic regression model yielding estimates for the probability of human RM specific to SBRT.
-
Technique for stereotactic body radiotherapy for spinal metastases
Journal of Clinical Neuroscience, 2011Co-Authors: Matthew Foote, Eric M Massicotte, Nancy La MacChia, Normand J. Laperriere, D. Hyde, Daniel Letourneau, Eugene Yu, Charles G Fisher, Raja Rampersaud, Stephen Lewis, Michael G. Fehlings, Arjun SahgalAbstract:Stereotactic body radiotherapy (SBRT) is an emerging technique for spinal tumours that is a natural succession to brain radiosurgery. The spine is an ideal site for SBRT due to its relative immobility and the potential clinical benefits of high dose delivery, particularly to optimise local control and avoid disease progression that can result in spinal cord compression. However, the proximity of the tumour to the spinal cord, with the potential for Radiation Myelopathy if the dose is delivered inaccurately or if the spinal cord dose limit is set too high, demands technical accuracy with Radiation Myelopathy a feared complication. Spine SBRT has been delivered with either a robotic-based linac system such as the Cyberknife, or with linac-based systems equipped with a multileaf collimator and image guidance system. Regardless of the technology, spine SBRT demands sophisticated treatment planning and delivery. This case-based technical review outlines the SBRT apparatus, planning and treatment delivery in use at the University of Toronto, Toronto, Canada. ?? 2010 Elsevier Ltd. All rights reserved.
-
Spinal cord tolerance for stereotactic body radiotherapy.
International Journal of Radiation Oncology Biology Physics, 2009Co-Authors: Arjun Sahgal, Vivian Weinberg, Eric L Chang, Scott G Soltys, Peter C Gerszten, Lijun Ma, Iris C. Gibbs, S. Wong, Jack F. FowlerAbstract:PURPOSE: Dosimetric data are reported for five cases of Radiation-induced Myelopathy after stereotactic body radiotherapy (SBRT) to spinal tumors. Analysis per the biologically effective dose (BED) model was performed. METHODS AND MATERIALS: Five patients with Radiation Myelopathy were compared to a subset of 19 patients with no Radiation Myelopathy post-SBRT. In all patients, the thecal sac was contoured to represent the spinal cord, and doses to the maximum point, 0.1-, 1-, 2-, and 5-cc volumes, were analyzed. The mean normalized 2-Gy-equivalent BEDs (nBEDs), calculated using an alpha/beta value of 2 for late toxicity with units Gy 2/2, were compared using the t test and analysis of variance test. RESULTS: Radiation Myelopathy was observed at the maximum point with doses of 25.6 Gy in two fractions, 30.9 Gy in three fractions, and 14.8, 13.1, and 10.6 Gy in one fraction. Overall, there was a significant interaction between patient subsets and volume based on the nBED (p = 0.0003). Given individual volumes, a significant difference was observed for the mean maximum point nBED (p = 0.01). CONCLUSIONS: The maximum point dose should be respected for spine SBRT. For single-fraction SBRT 10 Gy to a maximum point is safe, and up to five fractions an nBED of 30 to 35 Gy 2/2 to the thecal sac also poses a low risk of Radiation Myelopathy.
Jianing Wang - One of the best experts on this subject based on the ideXlab platform.
-
vascular endothelial growth factor enhanced the angiogenesis response of human umbilical cord derived mesenchymal stromal cells in a rat model of Radiation Myelopathy
Neurochemical Research, 2015Co-Authors: Jing Zhang, Jianing WangAbstract:The present study was designed to examine a synergistic role for VEGF and human umbilical cord-derived MSCs (UC-MSCs) therapy in a rat model of Radiation Myelopathy. UC-MSCs and VEGF were injected through the tail vein at 90, 97, 104 and 111 days post-irRadiation. Behavioral tests were performed, and histological damage was examined. The microcirculation in the spinal cord was assessed using von Willebrand factor immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β and tumor necrosis factor-α in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor and glial cell-derived neurotrophic factor in the spinal cord. The UC-MSCs processed with VEGF, including VEGF165-induced UC-MSC (iUC), VEGF and UC-MSCs (VEGF-UC), increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, raised the relative magnitude of spinal cord blood flow compared to UC-MSCs treatment alone. Our data provided the first evidence that vascular endothelial growth factor enhanced the angiogenesis response of human umbilical cord-derived mesenchymal stromal cells in a rat model of Radiation Myelopathy.
-
multiple injections of human umbilical cord derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of Radiation Myelopathy
Journal of Translational Medicine, 2014Co-Authors: Jing Zhang, Ke Zheng, Xiubin Xiao, Lei Wang, Feng Liang, Zailiang Yang, Yanqing Wang, Zhifang Li, Jianing WangAbstract:At present, no effective clinical treatment is available for the late effects of Radiation Myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of Radiation Myelopathy. An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irRadiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord. Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord. Multiple injections of UC-MSCs via the tail vein in a rat model of Radiation Myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
Timothy E Schultheiss - One of the best experts on this subject based on the ideXlab platform.
-
Spinal Cord Toxicity
Medical Radiology, 2011Co-Authors: Timothy E SchultheissAbstract:Radiation Myelopathy is a feared and generally avoidable complication of thoracic irRadiation. A better understanding of the Radiation response of the spinal cord and advances in Radiation therapy delivery techniques mean that this complication should be preventable in nearly all treatment situations. A better understanding of the pathogenesis of the injury has lead to the protection of the spinal cord from Radiation in experimental studies and to the possible treatment of Radiation Myelopathy.
-
Spinal cord Radiation tolerance
International Journal of Radiation Oncology Biology Physics, 1994Co-Authors: Timothy E SchultheissAbstract:Each case of Radiation Myelopathy represents a unique occurrence where an individual’s tolerance was exceeded. Therefore, each case offers the challenge to determine why this patient’s tolerance was exceeded at a dose that other patients tolerate. In Radiation oncology, we believe that higher doses invariably result in higher incidences of late complications and that this dose-response is largely a result of the increasing probability of the killing of cells. We also hold that cell death from Radiation is a stochastic event and consequently complications of Radiation are stochastic events in as much as they depend on cell death. However, dose is not the only factor that is causally related to Radiation Myelopathy, and it is not just the unlucky patient who experiences Radiation Myelopathy at doses tolerated by other patients. The factors that may reduce a patient’s Radiation tolerance may be identified through case control analysis, proportional hazards analysis, or certain multivariate regression methods. The proper methods of analysis depend on the exact nature set. In all cases, however, there must be some patients identified who share characteristics with the Myelopathy cases, but who did not develop the injury. The article in this issue by Wong et al. (8) is a report of a survey of the experience of the Princess Margaret Hospital/Ontario Cancer Institute which quotes data on Radiation Myelopathy cases alone. The information in this report would be of greater clinical use if some indication had been provided of the total number of patients from which the Myelopathy cases were drawn. Nonetheless, there are some useful measures of the incidence of Myelopathy provided in this study. There were 18 cases of Radiation Myelopathy after single courses of thoracic treatment. In 9 of these 18, a split course regimen ofgreater than 40 Gy in 10 fractions was given-a well-known Myelopathy-causing technique used mainly in the 1970s and now obsolete (1, 2, 4, 7). Historically, the dose regimen of 40 Gy in 10 fractions resulted in a 5-l 5% observed incidence of Radiation Myelopathy. Three of the remaining cases of thoracic Myelopathy were following multiple fractions per day; 5 others received 15 to 20 fractions with doses per fraction generally about 3 Gy. The only conventional fractionation schedule among the thoracic cases was 15 X 2 Gy followed by 10 X 2.5 Gy. These investigators found no case of Radiation Myelopathyfrom the Princess Margaret Hospital/Ontario Cancer Institute in a patient who received 50 Gy (either to the spinal cord or midline) in 25 ,fractions. The only case of cervical Myelopathy after 25 fractions or more occurred in a patient who received a dose of 60 Gy. Another case received 47.7 Gy in 20 fractions, and all other cervical Myelopathy cases involved high doses per fraction or multiple daily fractions. The evidence is now that 50 Gy in 25 fractions yields an incidence of Radiation Myelopathy less than 0.5% and probably less than 0.2% (5,6, 3). This estimate is probably valid for most cases where the dose is calculated to the midline as well. However, the dose to the spinal cord should be kept under 50 Gy (lower if possible) as long as the prescribed dose can be delivered reliably to the clinical target volume. This suggestion is offered so that the rare case, often involving patients with conditions that reduce the spinal cord tolerance, can be avoided. It is well understood that heterogeneity in a population decreases the steepness of dose-response functions. It is also clear that the doses typically delivered to the spinal cord during a course of Radiation treatment are in the flat portion of the dose-response function. Therefore, any case of Radiation Myelopathy resulting from conventionally fractionated treatments of about 50 Gy or less will likely be idiosyncratic and possibly as much a result of an individually low tolerance as of the dose to the spinal cord. For this reason, it would be helpful to pursue and report any factors that lead to reduced tolerance in such cases. A partial list of these factors includes hypertension, hypotension, acquired or congenital spinal defects, vascular diseases or vascular damage from diseases, and of course certain chemotherapeutic agents, Being aware of any of
-
Volume effects in Rhesus monkey spinal cord
International Journal of Radiation Oncology Biology Physics, 1994Co-Authors: Timothy E Schultheiss, Roger E Price, L. Clifton Stephens, Lester J PetersAbstract:Abstract Purpose: An experiment was conducted to test for the existence of a volume effect in Radiation Myelopathy using Rhesus monkeys treated with clinically relevant field sizes and fractionation schedules. Methods and Materials: Five groups of Rhesus monkeys were irradiated using 2.2 Gy per fraction to their spinal cords. Three groups were irradiated with 8 cm fields to total doses of 70.4, 77, and 83.6 Gy. Two additional groups were irradiated to 70.4 Gy using 4 and 16 cm fields. The incidence of paresis expressed within 2 years following the completion of treatment was determined for each group. Maximum likelihood estimation was used to determine parameters of a logistic dose response function. The volume effect was modeled using the probability model in which the probability of producing a lesion in an irradiated volume is governed by the probability of the occurrence of independent events. This is a two parameter model requiring only the estimates of the parameters of the doseresponse function for the reference volume, but not needing any additional parameters for describing the volume effect. Results: The probability model using a logistic dose-response function fits the data well with the D 50 = 75.8 Gy for the 8-cm field. No evidence was seen for a difference in sensitivities for different anatomical levels of the spinal cord. Most lesions were type 3, combined white matter parenchymal and vascular lesions. Latent periods did not differ significantly from those of type 3 lesions in humans. Conclusion: The spinal cord exhibits a volume effect that is well described by the probability model. Because the dose response function for Radiation Myelopathy is steep, the volume effect is modest The Rhesus monkey remains the animal model most similar to humans in dose response, histopathology, and latency for Radiation Myelopathy.
-
permanent Radiation Myelopathy
British Journal of Radiology, 1992Co-Authors: Timothy E Schultheiss, Clifton L StephensAbstract:Because of the morbidity and mortality associated with Radiation Myelopathy, Radiation injury to the spinal cord has been the subject of more clinical reports than any other normal-tissue injury. The spinal cord is perhaps second only to skin as the organ most frequently studied by radiobiologists. Its response has been investigated in mice, rats, cats, guinea pigs, rabbits, pigs, dogs, and rhesus monkeys—virtually every laboratory animal species. Given this level of attention, it is surprising what is not known about the Radiation response of the spinal cord. Relatively few animal studies have been performed on the effect of cytotoxic drugs on the Radiation response of the spinal cord, the age effects, the effects of blood pressure or other physiological conditions that are controllable in the laboratory, or the relative response of various anatomical levels of the spinal cord. In addition to these unresolved factors, the dose response in the human is still poorly defined. However, as a result of the att...
-
the pathogenesis of Radiation Myelopathy widening the circle
International Journal of Radiation Oncology Biology Physics, 1992Co-Authors: Timothy E Schultheiss, Clifton L StephensAbstract:The fact that the spinal cord can react to insult in a limited number of ways is again demonstrated in the article by Powers et al. (6). These authors show that the canine spinal cord reacts to Radiation in much the same way as other experimental animals and humans, and that dogs apparently have latent periods that are comparable with other large animals, with the exception of the pig, of course. The new findings in this report are the reactions of the meninges and the dorsal root ganglia. Although many attempts have been made to categorize Radiation lesions of the spinal cord, no classification scheme has met with wide spread acceptance. The reasoning behind the attempts at categorization is that better definition of the histopathology may assist in better understanding of the pathogenesis. The reasons that this effort has been largely unsuccessful are (a) not enough analysis as been directed at the changes during the latent period, (b) after the injury has advanced far enough to cause signs, the histological lesions are varied in both age and morphology, and (c) the pathogenesis of many different types of insult lead to similar lesions in the CNS. In pathology as in art, diferent interpretations can be given to the same image. The fundamentals of the pathology of Radiation Myelopathy are: the lesions are nearly always confined to the white matter; the primary lesions are confined to the irradiated portion of the cord with dying back and Wallerian degeneration occurring outside the field; a mononuclear inflammatory response is often observed, vascular changes may include hyaline thickening, telangiectasia, fibrinoid necrosis, vascular occlusion, focal hemorrhage, and hemorrhagic necrosis; parenchymal responses include demyelination and gliosis; and white matter necrosis may occur without apparently significant vascular injury. We would like to address each of these fundamentals in turn. Because of the overwhelming propensity for changes to occur in the white matter, it is unlikely that extramedullary arteries or arterioles are significantly involved in the pathogenesis. The grey matter is exquisitely sensitive to disruption of its oxygen supply and would show any such arterial changes to a greater degree than the white matter. Because lesions tend to be located in lateral motor tracts and edema is often found in active lesions, it can be argued effectively that the vascular related changes are more typical of a venous lesion than an arterial one. Some support for this argument can be found in the study by Reinhold et al. (8) who observed that Myelopathy patients had significantly lower blood pressure than the cohort of nonMyelopathy patients. The fact that the lesions of Radiation Myelopathy are confined to the irradiated field argues against a role for an autoimmune response. Furthermore, the autoimmune theory has difficulties explaining, as do other theories of the pathogenesis of this injury, why the white matter necrosis involves axonal degeneration as well as demyelination. The mononuclear inflammatory response that is frequently observed in Radiation lesions of the spinal cord seem to be a more common finding in human cases than in experimental animals. If this is true, then it may indicate that there is some difference in the pathogenesis between the human and animal models of human Radiation Myelopathy. Because it is difficult to differentiate between infiltrating blood monocytes and reactive resident microglia, it is not possible to determine what fraction of literature reports of mononuclear infiltrates represents a traditional inflammatory response and what fraction is a microglial response. The interpretation of inflammatory/ immune responses is further complicated by the fact that it is commonly impossible to differentiate lymphocytes from glial cells in sections of formalin-fixed paraffin embedded tissue (3). The vascular contribution to the Radiation damage of the spinal cord is still unresolved. The unambiguous vas-
Ke Zheng - One of the best experts on this subject based on the ideXlab platform.
-
demyelination occurred as the secondary damage following diffuse axonal loss in a rat model of Radiation Myelopathy
Neurochemical Research, 2017Co-Authors: Yong Zhou, Ke ZhengAbstract:The main purpose of the present study was to examine the time and dose-dependent course of demyelination in the rat Radiation Myelopathy model in the first 180 days after irRadiation of the spinal cord. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 50 Gy and 100 Gy, respectively. The behavioral dysfunction was observed by the forelimb paralysis scoring system. The histological damage in the irradiated spinal cord was examined by hematoxylin/eosin staining, luxol fast blue staining, immunohistochemical analysis, methylene blue/Azure II staining, and uranyl/lead salts staining. The gene expression of oligodendrocyte-related markers were also determined by quantitative real-time PCR. The complete loss of forelimb motor function in all animals was observed at 180 days 50 Gy post-irRadiation and at 120 days 100 Gy post-irRadiation. We demonstrated that a 50 and 100-Gy single-dose irRadiation of the C2-T2 spinal cord segment resulted in diffuse axonal loss and elicited secondary demyelination damage in the spinal cord. We further observed that 100-Gy irRadiation reduced the gene expression of myelin oligodendrocyte glycoprotein in irradiated spinal cord. Taken together, our data not only define diffuse axonal loss as the main histological damage but also provide the first evidence that demyelination occurred as the secondary damage in irradiated spinal cord.
-
intravenous injections of human mesenchymal stromal cells modulated the redox state in a rat model of Radiation Myelopathy
Evidence-based Complementary and Alternative Medicine, 2015Co-Authors: Jing Zhang, Lianbing Li, Jiayan Wu, Tao Wang, Jifan Yang, Ke Zheng, Shaolin LiAbstract:The main aim of the present study was to assess the antioxidative effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of Radiation Myelopathy. UC-MSCs were isolated from Wharton’s jelly (WJ) of umbilical cords. An irradiated cervical spinal cord rat model (C2-T2 segment) was generated using a 60Co irradiator to deliver 30 Gy of Radiation. UC-MSCs were injected through the tail vein at 90 days, 97 days, 104 days, and 111 days after-irRadiation. Histological damage was examined by cresyl violet/Nissl staining. The activities of two antioxidant enzymes catalase (CAT) and glutathione peroxidase (GPX) in the spinal cord were measured by the biomedical assay. In addition, the levels of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2) in the spinal cord were determined by ELISA methods. Multiple injections of UC-MSCs through the tail vein ameliorated neuronal damage in the spinal cord, increased the activities of the antioxidant enzymes CAT and GPX, and increased the levels of VEGF and Ang-2 in the spinal cord. Our results suggest that multiple injections of UC-MSCs via the tail vein in the rat model of Radiation Myelopathy could significantly improve the antioxidative microenvironment in vivo.
-
multiple injections of human umbilical cord derived mesenchymal stromal cells through the tail vein improve microcirculation and the microenvironment in a rat model of Radiation Myelopathy
Journal of Translational Medicine, 2014Co-Authors: Jing Zhang, Ke Zheng, Xiubin Xiao, Lei Wang, Feng Liang, Zailiang Yang, Yanqing Wang, Zhifang Li, Jianing WangAbstract:At present, no effective clinical treatment is available for the late effects of Radiation Myelopathy. The aim of the present study was to assess the therapeutic effects of human umbilical cord-derived mesenchymal stromal cells (UC-MSCs) in a rat model of Radiation Myelopathy. An irradiated cervical spinal cord rat model was generated. UC-MSCs were injected through the tail vein at 90, 97, 104 and 111 days post-irRadiation. Behavioral tests were performed using the forelimb paralysis scoring system, and histological damage was examined using Nissl staining. The microcirculation in the spinal cord was assessed using von Willebrand factor (vWF) immunohistochemical analysis and laser-Doppler flowmetry. The microenvironment in the spinal cord was determined by measuring the pro-inflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the serum and the anti-inflammatory cytokines brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) in the spinal cord. Multiple injections of UC-MSCs through the tail veil decreased the forelimb paralysis, decreased spinal cord histological damage, increased the number of neurons in the anterior horn of the spinal cord, increased the endothelial cell density and the microvessel density in the white matter and gray matter of the spinal cord, increased the relative magnitude of spinal cord blood flow, down-regulated pro-inflammatory cytokine expression in the serum, and increased anti-inflammatory cytokine expression in the spinal cord. Multiple injections of UC-MSCs via the tail vein in a rat model of Radiation Myelopathy significantly improved the microcirculation and microenvironment through therapeutic paracrine effects.
