Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique

2004 ◽  
Vol 1 (3) ◽  
pp. 330-337 ◽  
Author(s):  
Ajay Bakshi ◽  
Corey Hunter ◽  
Sharon Swanger ◽  
Angelo Lepore ◽  
Itzhak Fischer
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Minimally Invasive ◽  
Lumbar Puncture ◽  
Therapeutic Potential ◽  
Invasive Technique ◽  
Injured Spinal Cord ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

Object. Stem cell therapy has been shown to have considerable therapeutic potential for spinal cord injuries (SCIs); however, most experiments in animals have been performed by injecting cells directly into the injured parenchyma. This invasive technique compromises the injured spinal cord, although it delivers cells into the hostile environment of the acutely injured cord. In this study, the authors tested the possibility of delivering stem cells to injured spinal cord by using three different minimally invasive techniques. Methods. Bone marrow stromal cells (BMSCs) are clinically attractive because they have shown therapeutic potential in SCI and can be obtained in patients at the bedside, raising the possibility of autologous transplantation. In this study transgenically labeled cells were used for transplantation, facilitating posttransplantation tracking. Inbred Fisher-344 rats received partial cervical hemisection injury, and 2 × 106 BMSCs were intravenously, intraventricularly, or intrathecally transplanted 24 hours later via lumbar puncture (LP). The animals were killed 3, 10, or 14 days posttransplantation, and tissue samples were submitted to histochemical and immunofluorescence analyses. For additional comparison and validation, lineage restricted neural precursor (LRNP) cells obtained from E13.5 rat embryos were transplanted via LP, and these findings were also analyzed. Conclusions. Both BMSCs and LRNP cells home toward injured spinal cord tissues. The use of LP and intraventricular routes allows more efficient delivery of cells to the injured cord compared with the intravenous route. Stem cells delivered via LP for treatment of SCI may potentially be applicable in humans after optimal protocols and safety profiles are established in further studies.

Presence and significance of CD-95 (Fas/APO1) expression after spinal cord injury

2001 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Isabel Zurita
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Gray Matter ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Content Type ◽  
Cord Injury ◽  
Positive Immunostaining ◽  
Fine Print

Object. A glycoprotein, CD95 (Fas/APO1) is widely considered to be implicated in the development of apoptosis in a number of tissues. Based on the hypothesis that apoptosis is related to cell death after spinal cord injury (SCI), the authors studied the presence and distribution of CD95 (Fas/APO1)-positive cells in injured spinal cord tissue for the purpose of determining the significance of this protein during the early phases of SCI. Methods. The presence and distribution of cells showing positive immunostaining for CD95 (Fas/APO1) were studied 1, 4, 8, 24, 48, and 72 hours and 1, 2, and 4 weeks after induction of experimental SCI in rats. Studies were conducted using a monoclonal antibody to the CD95 (Fas/APO1) protein. Positivity for CD95 (Fas/APO1) was observed in apoptotic cells, mainly in the gray matter, 1 hour after trauma, and the number of immunostained cells increased for the first 8 hours, at which time the protein was expressed in both gray and white matter. From 24 to 72 hours postinjury, the number of immunostained cells decreased in the gray matter, but increased in the white matter. From then on, there were fewer CD95 (Fas/APO1)-positive cells, but some cells in the white matter still exhibited positive immunostaining 1 and 2 weeks after injury. At 4 weeks, there remained no CD95 (Fas/APO1)-positive cells in injured spinal cord. Conclusions. These findings indicate that CD95 (Fas/APO1) is expressed after SCI, suggesting a role for this protein in the development of apoptosis after trauma and the possibility of a new therapeutic approach to SCI based on blocking the CD95 (Fas/APO1) system.

Microangiographic study of experimental spinal cord injuries

1971 ◽  
Vol 35 (3) ◽  
pp. 277-286 ◽  
Author(s):  
David J. Fairholm ◽  
Ian M. Turnbull
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Axonal Degeneration ◽  
Spinal Cord Injuries ◽  
Spinal Injury ◽  
Degenerative Changes ◽  
Injured Spinal Cord ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

✓ The pathology of spinal cord injury has been studied in 34 rabbits and 5 dogs with attention focused on the condition of the microvasculature during the evolution of neuronal and axonal degeneration and necrosis. The animals were killed and perfused arterially with colloidal barium from 10 min to 14 days after a controlled spinal injury. Microradiographs of the injured tissues were obtained and compared with corresponding histological sections. Microangiography at 7 to 14 days defines two zones in the injured spinal cord. Zone 1 is located in the posterocentral part of the cord. Capillaries in this region progressively lose their ability to conduct blood and perfusate over the first 4 hours. Degenerative changes in neurons are visible by 1 hour after injury. Necrosis of all elements including capillaries ensues. Zone 2 surrounds Zone 1. Microvascular patterns are normal in Zone 2 although neuronal and axonal degeneration is severe. Pericapillary hemorrhages which occur as early as 10 min after injury in Zone 1 and become progressively larger over the first 4 hours seldom are seen in Zone 2. The evidence indicates that at all times in the pathogenesis of spinal cord injury the microvasculature in Zone 2 is capable of perfusion. Degeneration of neural structures either precedes microvascular breakdown (Zone 1) or occurs in the absence of microvascular disruption (Zone 2). Recovery of damaged neurons and axons depends upon a preserved microcirculation.

Effects of dexamethasone on apoptosis-related cell death after spinal cord injury

2002 ◽  
Vol 96 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Santiago Oya ◽  
Carmen Morales
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Glial Cells ◽  
Spinal Cord Tissue ◽  
Injured Spinal Cord ◽  
Content Type ◽  
Related Cell ◽  
Cord Injury ◽  
Fine Print

Object. The purpose of this study was to analyze the expression of F7–26 (Apostain) in injured spinal cord tissue, and the modifying effects of dexamethasone administration. Methods. A total of 56 adult female Wistar rats were subjected to traumatic spinal cord injury (SCI) to induce complete paraplegia. These rats were divided into two groups according to whether they received dexamethasone (doses of 1 mg/kg daily) post-SCI. Injured spinal cord tissue was studied by means of conventional histological techniques, and Apostain expression was determined by immunohistochemical analysis at 1, 4, 8, 24, and 72 hours, and at 1 and 2 weeks after SCI in all the animals. Apostain-positive cells, mainly neurons and glial cells, were detected 1 hour after injury, peaking at 8 hours, after which the number decreased. One week after injury, apoptosis was limited to a few glial cells, mainly oligodendrocytes, and 2 weeks after injury there was no evidence of Apostain-positive cells. In the group of paraplegic rats receiving post-SCI intraperitoneal dexamethasone, there was a significant decrease in the number of Apostain-positive cells. Conclusions. Analysis of the results indicated that apoptosis plays a role in the early period after SCI and that administration of dexamethasone decreases apoptosis-related cell death in the injured spinal cord tissue.

Stem Cell Transplantation: A Promising Therapy for Spinal Cord Injury

2020 ◽  
Vol 15 (4) ◽  
pp. 321-331 ◽  
Author(s):  
Zhe Gong ◽  
Kaishun Xia ◽  
Ankai Xu ◽  
Chao Yu ◽  
Chenggui Wang ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Spinal Cord Injury ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Therapeutic Potential ◽  
Embryonic Stem ◽  
Current Status ◽  
Cord Injury

Spinal Cord Injury (SCI) causes irreversible functional loss of the affected population. The incidence of SCI keeps increasing, resulting in huge burden on the society. The pathogenesis of SCI involves neuron death and exotic reaction, which could impede neuron regeneration. In clinic, the limited regenerative capacity of endogenous cells after SCI is a major problem. Recent studies have demonstrated that a variety of stem cells such as induced Pluripotent Stem Cells (iPSCs), Embryonic Stem Cells (ESCs), Mesenchymal Stem Cells (MSCs) and Neural Progenitor Cells (NPCs) /Neural Stem Cells (NSCs) have therapeutic potential for SCI. However, the efficacy and safety of these stem cellbased therapy for SCI remain controversial. In this review, we introduce the pathogenesis of SCI, summarize the current status of the application of these stem cells in SCI repair, and discuss possible mechanisms responsible for functional recovery of SCI after stem cell transplantation. Finally, we highlight several areas for further exploitation of stem cells as a promising regenerative therapy of SCI.

The effects of methylprednisolone and the ganglioside GM1 on acute spinal cord injury in rats

1994 ◽  
Vol 80 (1) ◽  
pp. 97-111 ◽  
Author(s):  
Shlomo Constantini ◽  
Wise Young
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Body Weight Loss ◽  
Ganglioside Gm1 ◽  
Rat Spinal Cord ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Human Spinal Cord ◽  
Cord Injury ◽  
Fine Print

✓ Recent clinical trials have reported that methylprednisolone sodium succinate (MP) or the monosialic ganglioside GM1 improves neurological recovery in human spinal cord injury. Because GM1 may have additive or synergistic effects when used with MP, the authors compared MP, GM1, and MP+GM1 treatments in a graded rat spinal cord contusion model. Spinal cord injury was caused by dropping a rod weighing 10 gm from a height of 1.25, 2.5, or 5.0 cm onto the rat spinal cord at T-10, which had been exposed via laminectomy. The lesion volumes were quantified from spinal cord Na and K shifts at 24 hours after injury and the results were verified histologically in separate experiments. A single dose of MP (30 mg/kg), given 5 minutes after injury, reduced 24-hour spinal cord lesion volumes by 56% (p = 0.0052), 28% (p = 0.0065), and 13% (p > 0.05) in the three injury-severity groups, respectively, compared to similarly injured control groups treated with vehicle only. Methylprednisolone also prevented injury-induced hyponatremia and increased body weight loss in the spine-injured rats. When used alone, GM1 (10 to 30 mg/kg) had little or no effect on any measured variable compared to vehicle controls; when given concomitantly with MP, GM1 blocked the neuroprotective effects of MP. At a dose of 3 mg/kg, GM1 partially prevented MP-induced reductions in lesion volumes, while 10 to 30 mg/kg of GM1 completely blocked these effects of MP. The effects of MP on injury-induced hyponatremia and body weight loss were also blocked by GM1. Thus, GM1 antagonized both central and peripheral effects of MP in spine-injured rats. Until this interaction is clarified, the authors recommend that MP and GM1 not be used concomitantly to treat acute human spinal cord injury. Because GM1 modulates protein kinase activity, protein kinases inhibit lipocortins, and lipocortins mediate anti-inflammatory effects of glucocorticoids, it is proposed that the neuroprotective effects of MP are partially due to anti-inflammatory effects and that GM1 antagonizes the effects of MP by inhibiting lipocortin. Possible beneficial effects of GM1 reported in central nervous system injury may be related to the effects on neural recovery rather than acute injury processes.

Minimally invasive implantation of epidural spinal cord neurostimulator electrodes by using a tubular retractor system

2004 ◽  
Vol 100 (6) ◽  
pp. 1119-1121 ◽  
Author(s):  
Matthew R. Johnson ◽  
Daniel J. Tomes ◽  
John S. Treves ◽  
Lyal G. Leibrock
Keyword(s):  
Spinal Cord ◽  
Postoperative Pain ◽  
Minimally Invasive ◽  
Intractable Pain ◽  
Tubular Retractor ◽  
Content Type ◽  
Novel Technique ◽  
Pain Syndromes ◽  
Hospital Stays ◽  
Fine Print

✓ The authors describe a novel technique for the implantation of multipolar epidural spinal cord neurostimulator electrodes with the aid of a tubular retractor system. Spinal cord neurostimulation is used as a neuroaugmentive tool for treating chronic intractable pain syndromes. Minimally invasive placement of the multipolar neurostimulator electrodes may allow for shorter hospital stays and less postoperative pain associated with the incision.

Therapeutic trial of hypercarbia and hypocarbia in acute experimental spinal cord injury

1984 ◽  
Vol 61 (5) ◽  
pp. 925-930 ◽  
Author(s):  
Ronald W. J. Ford ◽  
David N. Malm
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Injuries ◽  
Mortality Rates ◽  
Therapeutic Trial ◽  
Tissue Preservation ◽  
Content Type ◽  
Experimental Spinal Cord Injury ◽  
Cord Injury ◽  
Fine Print

✓ Hypocarbia, normocarbia, or hypercarbia was maintained for an 8-hour period beginning 30 minutes after acute threshold spinal cord injuries in cats. No statistically significant differences in neurological recovery or histologically assessed tissue preservation were found among the three groups of animals 6 weeks after injury. No animal recovered the ability to walk. It is concluded that maintenance of hypercarbia or hypocarbia during the early postinjury period is no more therapeutic than maintenance of normocarbia. Mortality rates and tissue preservation data suggest, however, that postinjury hypocarbia may be less damaging than hypercarbia.

Ultrastructural scoring of graded acute spinal cord injury in the rat

2002 ◽  
Vol 97 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Selcuk Palaoglu ◽  
H. Selcuk Surucu ◽  
Mutlu Hayran ◽  
Etem Beskonakli
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Behavioral Assessment ◽  
Traumatic Injury ◽  
Significant Negative Correlation ◽  
Content Type ◽  
Cord Injury ◽  
Contusion Injury ◽  
Weight Drop ◽  
Fine Print

Object. There is a need for an accurate quantitative histological technique that also provides information on neurons, axons, vascular endothelium, and subcellular organelles after spinal cord injury (SCI). In this paper the authors describe an objective, quantifiable technique for determining the severity of SCI. The usefulness of ultrastructural scoring of acute SCI was assessed in a rat model of contusion injury. Methods. Spinal cords underwent acute contusion injury by using varying weights to produce graded SCI. Adult Wistar rats were divided into five groups. In the first group control animals underwent laminectomy only, after which nontraumatized spinal cord samples were obtained 8 hours postsurgery. The weight-drop technique was used to produce 10-, 25-, 50-, and 100-g/cm injuries. Spinal cord samples were also obtained in the different trauma groups 8 hours after injury. Behavioral assessment and ultrastructural evaluation were performed in all groups. When the intensity of the traumatic injury was increased, behavioral responses showed a decreasing trend. A similar significant negative correlation was observed between trauma-related intensity and ultrastructural scores. Conclusions. In the present study the authors characterize quantitative ultrastructural scoring of SCI in the acute, early postinjury period. Analysis of these results suggests that this method is useful in evaluating the degree of trauma and the effectiveness of pharmacotherapy in neuroprotection studies.

The therapeutic window for spinal cord decompression in a rat spinal cord injury model

2005 ◽  
Vol 3 (4) ◽  
pp. 302-307 ◽  
Author(s):  
Christopher B. Shields ◽  
Y. Ping Zhang ◽  
Lisa B. E. Shields ◽  
Yingchun Han ◽  
Darlene A. Burke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Stenosis ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Therapeutic Window ◽  
Content Type ◽  
Significant Difference ◽  
Cord Injury ◽  
Fine Print

Object. There are no clinically based guidelines to direct the spine surgeon as to the proper timing to undertake decompression after spinal cord injury (SCI) in patients with concomitant stenosis-induced cord compression. The following three factors affect the prognosis: 1) severity of SCI; 2) degree of extrinsic spinal cord compression; and 3) duration of spinal cord compression. Methods. To elucidate further the relationship between varying degrees of spinal stenosis and a mild contusion-induced SCI (6.25 g-cm), a rat SCI/stenosis model was developed in which 1.13- and 1.24-mm-thick spacers were placed at T-10 to create 38 and 43% spinal stenosis, respectively. Spinal cord damage was observed after the stenosis—SCI that was directly proportional to the duration of spinal cord compression. The therapeutic window prior to decompression was 6 and 12 hours in the 43 and 38% stenosis—SCI lesions, respectively, to maintain locomotor activity. A significant difference in total lesion volume was observed between the 2-hour and the delayed time(s) to decompression (38% stenosis—SCI, 12 and 24 hours, p < 0.05; 43% stenosis—SCI, 24 hours, p < 0.05) indicating a more favorable neurological outcome when earlier decompression is undertaken. This finding was further supported by the animal's ability to support weight when decompression was performed by 6 or 12 hours compared with 24 hours after SCI. Conclusions. Analysis of the findings in this study suggests that early decompression in the rat improves locomotor function. Prolongation of the time to decompression may result in irreversible damage that prevents locomotor recovery.

Cruciate paralysis

1986 ◽  
Vol 65 (1) ◽  
pp. 108-110 ◽  
Author(s):  
Daniel Dumitru ◽  
James E. Lang
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rare Case ◽  
Motor Vehicle ◽  
Motor Vehicle Accident ◽  
Cervical Spinal Cord ◽  
Content Type ◽  
Vehicle Accident ◽  
Cord Injury ◽  
Fine Print

✓ A rare case of cruciate paralysis is reported in a 39-year-old man following a motor-vehicle accident. The differentiation of this syndrome from a central cervical spinal cord injury is delineated.

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