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.

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.

Effect of anti—rat interleukin-6 antibody after spinal cord injury in the rat: inducible nitric oxide synthase expression, sodium- and potassium-activated, magnesium-dependent adenosine-5′-triphosphatase and superoxide dismutase activation, and ultrastructural changes

2001 ◽  
Vol 95 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Metin Tuna ◽  
Sait Polat ◽  
Tahsin Erman ◽  
Faruk Ildan ◽  
A. Iskender Göçer ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Tissue ◽  
Inos Activity ◽  
Content Type ◽  
Cord Injury ◽  
Oxide Synthase ◽  
Fine Print ◽  
Inducible Nitric Oxide

Object. The inflammatory cells that accumulate at the damaged site after spinal cord injury (SCI) may secrete interleukin-6 (IL-6), a mediator known to induce the expression of inducible nitric oxide synthase (iNOS). Any increased production of NO by iNOS activity would aggravate the primary neurological damage in SCI. If this mechanism does occur, the direct or indirect effects of IL-6 antagonists on iNOS activity should modulate this secondary injury. In this study, the authors produced spinal cord damage in rats and applied anti—rat IL-6 antibody to neutralize IL-6 bioactivity and to reduce iNOS. They determined the spinal cord tissue activities of Na+-K+/Mg++ adenosine-5′-triphosphatase (ATPase) and superoxide dismutase, evaluated iNOS immunoreactivity, and examined ultrastructural findings to assess the results of this treatment. Methods. Seventy rats were randomly allocated to four groups. Group I (10 rats) were killed to provide normal spinal cord tissue for testing. In Group II 20 rats underwent six-level laminectomy for the effects of total laminectomy alone to be determined. In Group III 20 rats underwent six-level T2–7 laminectomy and SCI was produced by extradural compression of the exposed cord. The same procedures were performed in the 20 Group IV rats, but these rats also received one (2 µg) intraperitoneal injection of anti—rat IL-6 antibody immediately after the injury and a second dose 24 hours posttrauma. Half of the rats from each of Groups II through IV were killed at 2 hours and the other half at 48 hours posttrauma. The exposed cord segments were immediately removed and processed for analysis. Conclusions. The results showed that neutralizing IL-6 bioactivity with anti—rat IL-6 antibody significantly attenuates iNOS activity and reduces secondary structural changes in damaged rat spinal cord tissue.

Ischemia in primate spinal cord injury

1971 ◽  
Vol 34 (5) ◽  
pp. 614-617 ◽  
Author(s):  
George E. Locke ◽  
David Yashon ◽  
Robert A. Feldman ◽  
William E. Hunt
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Lactic Acid ◽  
Rhesus Monkeys ◽  
Spinal Cord Tissue ◽  
Time Intervals ◽  
Content Type ◽  
Lactate Accumulation ◽  
Cord Injury ◽  
Fine Print

✓ Lactate accumulation in spinal cord tissue following trauma was determined to ascertain the role and magnitude of ischemia. High thoracic and low thoracic laminectomies were performed on each of nine rhesus monkeys. The lower exposed cord was traumatized with a calibrated blow of 300 gm cm. The upper exposed cord served as a nontraumatized control. At time intervals of 1.5 min to 48 hrs after trauma, both cord segments were removed and assayed for lactic acid. Lactate in nontraumatized segments averaged 3.64 mM/kg tissue, with a range of 2.20 to 4.95. Lactate in traumatized segments removed in from 1.5 min to 12 hrs from six monkeys averaged 5.50 mM/kg tissue, with a range of 4.32 to 6.46. Lactate in traumatized segments from three monkeys 18 to 40 hrs after trauma averaged 4.07 mM/kg, with a range of 3.20 to 5.18. This finding supports the concept that ischemia plays a role early in the traumatic process in spinal cord injury.

Late recovery following spinal cord injury

2002 ◽  
Vol 97 (2) ◽  
pp. 252-265 ◽  
Author(s):  
John W. McDonald ◽  
Daniel Becker ◽  
Cristina L. Sadowsky ◽  
John A. Jane ◽  
Thomas E. Conturo ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Neural Activity ◽  
Recovery Of Function ◽  
Spinal Injury ◽  
Single Case ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

✓ The authors of this prospective, single-case study evaluated the potential for functional recovery from chronic spinal cord injury (SCI). The patient was motor complete with minimal and transient sensory perception in the left hemibody. His condition was classified as C-2 American Spinal Injury Association (ASIA) Grade A and he had experienced no substantial recovery in the first 5 years after traumatic SCI. Clinical experience and evidence from the scientific literature suggest that further recovery would not take place. When the study began in 1999, the patient was tetraplegic and unable to breathe without assisted ventilation; his condition classification persisted as C-2 ASIA Grade A. Magnetic resonance imaging revealed severe injury at the C-2 level that had left a central fluid-filled cyst surrounded by a narrow donutlike rim of white matter. Five years after the injury a program known as “activity-based recovery” was instituted. The hypothesis was that patterned neural activity might stimulate the central nervous system to become more functional, as it does during development. Over a 3-year period (5–8 years after injury), the patient's condition improved from ASIA Grade A to ASIA Grade C, an improvement of two ASIA grades. Motor scores improved from 0/100 to 20/100, and sensory scores rose from 5–7/112 to 58–77/112. Using electromyography, the authors documented voluntary control over important muscle groups, including the right hemidiaphragm (C3–5), extensor carpi radialis (C-6), and vastus medialis (L2–4). Reversal of osteoporosis and an increase in muscle mass was associated with this recovery. Moreover, spasticity decreased, the incidence of medical complications fell dramatically, and the incidence of infections and use of antibiotic medications was reduced by over 90%. These improvements occurred despite the fact that less than 25 mm2 of tissue (approximately 25%) of the outer cord (presumably white matter) had survived at the injury level. The primary novelty of this report is the demonstration that substantial recovery of function (two ASIA grades) is possible in a patient with severe C-2 ASIA Grade A injury, long after the initial SCI. Less severely injured (lower injury level, clinically incomplete lesions) individuals might achieve even more meaningful recovery. The role of patterned neural activity in regeneration and recovery of function after SCI therefore appears a fruitful area for future investigation.

Evaluation of the neuroprotective effects of sodium channel blockers after spinal cord injury: improved behavioral and neuroanatomical recovery with riluzole

2001 ◽  
Vol 94 (2) ◽  
pp. 245-256 ◽  
Author(s):  
Gwen Schwartz ◽  
Michael G. Fehlings
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
White Matter ◽  
Neurological Recovery ◽  
Therapeutic Effects ◽  
Channel Blockers ◽  
Content Type ◽  
Cord Injury ◽  
Residual Tissue ◽  
Fine Print

Object. Persistent activation of voltage-sensitive Na+ channels is associated with cellular toxicity and may contribute to the degeneration of neural tissue following traumatic brain and spinal cord injury (SCI). Pharmacological blockade of these channels can attenuate secondary pathophysiology and reduce functional deficits acutely. Methods. To determine the therapeutic effects of Na+ channel blockers on long-term tissue sparing and functional neurological recovery after traumatic SCI, the authors injected Wistar rats intraperitoneally with riluzole (5 mg/kg), phenytoin (30 mg/kg), CNS5546A, a novel Na+ channel blocker (15 mg/kg), or vehicle (2-HPβCD; 5 mg/kg) 15 minutes after induction of compressive SCI at C7—T1. Functional neurological recovery of coordinated hindlimb function and strength, assessed 1 week postinjury and weekly thereafter for 6 weeks, was significantly enhanced in animals treated with riluzole compared with the other treatment groups. Seven weeks postinjury the preservation of residual tissue and integrity of descending axons were determined with digital morphometrical and fluorescent histochemical analysis. All three Na+ channel blockers significantly enhanced residual tissue area at the injury epicenter compared with control. Riluzole significantly reduced tissue loss in rostrocaudal regions surrounding the epicenter, with overall sparing of gray matter and selective sparing of white matter. Also, counts of red nuclei neurons retrogradely labeled with fluorogold introduced caudal to the injury site were significantly increased in the riluzole group. Conclusions. Systemic Na+ channel blockers, in particular riluzole, can confer significant neuroprotection after in vivo SCI and result in behavioral recovery and sparing of both gray and white matter.

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.

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.

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.

Sign in / Sign up

Export Citation Format

Share Document