Neuroprotective effects of GYKI 52466 on experimental spinal cord injury in rats

2003 ◽  
Vol 98 (3) ◽  
pp. 275-281 ◽  
Author(s):  
Ahmet Çolak ◽  
Osman Soy ◽  
Hafize Uzun ◽  
Özcan Aslan ◽  
Seref Barut ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuroprotective Effects ◽  
Content Type ◽  
Gyki 52466 ◽  
Cord Injury ◽  
Group 3 ◽  
The Mean ◽  
Group 2 ◽  
Spinal Cord Injured ◽  
Fine Print

Object. The toxic effects of glutamate in the central nervous system are well known. This neurotoxicity occurs through metabotropic and ionotropic receptors, the latter group composed of N-methyl-d-aspartate, α-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and kainate receptors. The authors investigated the neuroprotective effects of GYKI 52466, a 2,3-benzodiazepine that is a selective and potent AMPA receptor antagonist, in a rat spinal cord trauma model. Methods. Sixty Wistar albino rats were studied in three groups of 20 animals each: sham-operated controls (Group 1); spinal cord—injured rats (Group 2); and spinal cord—injured plus GYKI 52466—treated rats (Group 3). In Groups 2 and 3, spinal cord injury (SCI) was induced at the thoracic level by applying an aneurysm clip to the cord for 1 minute. One minute after the clip was removed, the rats in Group 3 received an intraperitoneal injection of 15 mg/kg GYKI 52466. Responses to injury and treatment were evaluated based on biochemical parameters (lipid peroxidation and adenosine 5′-triphosphate [ATP] levels in tissue), and on light and transmission electron microscopy findings in cord tissue collected at different times post-SCI. Five rats from each group underwent assessment of functional recovery at 1, 3, and 5 days after SCI; evaluation was performed using the inclined-plane technique and Tarlov motor grading scale. The mean lipid peroxidation levels in Groups 1 and 2 were 21.73 ± 4.35 and 35.53 ± 2.99 nmol/g of wet tissue, respectively. The level in Group 3 was 27.98 ± 3.93 nmol/g of wet tissue, which was significantly lower than that in Group 2 (p < 0.01). The mean ATP levels in Groups 1 and 2 were 166.21 ± 25.57 and 41.72 ± 12.28 nmol/g of wet tissue, respectively. The ATP level in Group 3 was 85.82 ± 13.92 nmol/g of wet tissue, which was significantly higher than that in Group 2 (p < 0.01). Light microscopic examination of Group 2 tissues showed hemorrhage, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. In contrast, the examination of Group 3 tissues showed limited hemorrhage and no necrosis or vascular thrombi. The most prominent findings in Group 2 were hemorrhage and necrosis, whereas the most prominent findings in Group 3 were focal hemorrhage and leukocyte infiltration. Electron microscopy demonstrated that GYKI 52466 protected the neurons, myelin, axons, and intracellular organelles. The mean inclined-plane angles in Groups 1, 2, and 3 were 65°, 40 to 45°, and 55°, respectively. Motor scale results in all groups showed a similar trend. Conclusions. The findings in this rat model suggest that GYKI 52466 may provide significant therapeutic protection from secondary damage after acute SCI. This agent may be a viable alternative treatment for SCI.

Neuroprotection and functional recovery after application of the caspase-9 inhibitor z-LEHD-fmk in a rat model of traumatic spinal cord injury

2005 ◽  
Vol 2 (3) ◽  
pp. 327-334 ◽  
Author(s):  
Ahmet Çolak ◽  
Alper Karaoǧlan ◽  
Şeref Barut ◽  
Sibel Köktürk ◽  
Aysşenur Iǧdem Akyildiz ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Cell Death ◽  
Rat Model ◽  
Caspase 9 ◽  
Content Type ◽  
Cord Injury ◽  
Group 3 ◽  
Group 2 ◽  
Fine Print

Object. Apoptosis is considered one of the most significant mechanisms in the pathogenesis of neuronal damage after spinal cord injury (SCI). This form of cell death occurs via mediators known as caspases. The aim of this study was to evaluate the neuroprotective effect of the caspase-9 inhibitor, z-LEHD-fmk, in a rat model of spinal cord trauma. Methods. Fifty-four Wistar albino rats were studied in the following three groups of 18 animals each: sham-operated controls (Group 1); trauma-only controls (Group 2); and trauma combined with z-LEHD-fmk—treated animals (0.8 µM/kg; Group 3). Spinal cord injury was produced at the thoracic level by using the weight-drop technique. Responses to SCI and the efficacy of z-LEHD-fmk treatment were determined on the basis of terminal deoxynucleotidyl transferase—mediated deoxyuridine triphosphate nick—end labeling staining and light and electron microscopy findings in cord tissue at 24 hours and 7 days posttrauma. Six rats from each group were also assessed for functional recovery at 3 and 7 days after SCI. This was conducted using the inclined-plane technique and a modified version of the Tarlov motor grading scale. At 24 hours postinjury, light microscopic examination of Group 2 tissue samples showed hemorrhage, edema, necrosis, polymorphonuclear leukocyte infiltration, and vascular thrombi. Those obtained in Group 3 rats at this stage showed similar features. At 24 hours postinjury, the mean apoptotic cell count in Group 2 was significantly higher than that in Group 3 (90.25 ± 2.6 and 50.5 ± 1.9, respectively; p < 0.05). At 7 days postinjury, the corresponding mean apoptotic cell counts were 49 ± 2.1 and 17.7 ± 2.6, also a significant difference (p < 0.05). Electron microscopy findings confirmed the occurrence of programmed cell death in different cell types in the spinal cord and showed that z-LEHD-fmk treatment protected neurons, glia, myelin, axons, and intracellular organelles. Conclusions. Examination of the findings in this rat model of SCI revealed that apoptosis occurs not only in neurons and astrocytes but also in oligodendrocytes and microglia. Furthermore, immediate treatment with the caspase-9 inhibitor z-LEHD-fmk blocked apoptosis effectively and was associated with better functional outcome. More in-depth research of the role of programmed cell death in spinal cord trauma and further study of the ways in which caspases are involved in this process may lead to new strategies for treating 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.

Oscillating field stimulation for complete spinal cord injury in humans: a Phase 1 trial

2005 ◽  
Vol 2 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Scott Shapiro ◽  
Richard Borgens ◽  
Robert Pascuzzi ◽  
Karen Roos ◽  
Michael Groff ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Upper Extremity ◽  
Phase 1 ◽  
Wilcoxon Test ◽  
Content Type ◽  
Cord Injury ◽  
Asia Score ◽  
The Mean ◽  
Fine Print

Object. An electrical field cathode (negative pole) has trophic and tropic effects on injured spinal cord axons in in vitro and in vivo models of sea lamprey, rodent, and canine spinal cord injury (SCI) and it improves functional outcome. A human oscillating field stimulator (OFS) was built, a Food and Drug Administration (FDA) exemption number was obtained, and institutional review board approval was given for a Phase 1 trial to study 10 humans with complete motor and sensory SCI. Methods. Entry criteria were complete SCI between C-5 and T-10 in patients 18 to 65 years of age and no transection demonstrated on magnetic resonance imaging. All participants received the National Acute Spinal Cord Injury Study (NASCIS) III methylprednisilone protocol. Cord compression and/or vertebral instability was treated before study entry. After treatment complete SCI (according to the American Spinal Injury Association [ASIA] score) remained in all patients with no somatosensory evoked potentials (SSEPs) below the injury level after surgery or for 48 hours. All patients underwent implantation of the OFS within 18 days. Patients underwent evaluation every 2 weeks postimplantation; the OFS was explanted at 15 weeks. Independent neurological status was assessed based on the ASIA score, visual analog scale (VAS) pain score, and SSEPs at 6 weeks, 6 months, and 1 year. Statistical analyses were performed using the two-tailed Wilcoxon test and analysis of variance (ANOVA). There were no complications at insertion of the OFS; there was one case of wound infection after explantation (5% infection rate). One patient was lost to follow up after 6 months. In all 10 patients the mean VAS pain score was 8 at implantation, 2 at 6 months, and in the nine attending follow up for 1 year it remained 2. At 1 year, the mean improvement in light touch was 25.5 points (ANOVA p < 0.001, Wilcoxon test p = 0.02), the mean improvement in pinprick sensation was 20.4 points (ANOVA p < 0.001, Wilcoxon test p = 0.02), and the mean improvement in motor status was 6.3 points (ANOVA p < 0.01, Wilcoxon test p = 0.02). Of five cases involving cervical cord injuries, bilateral upper-extremity SSEPs were normal in one, unilateral upper-extremity SSEPs were recovered in four, bilateral upper-extremity SSEPs were recovered in one, and abnormal lower-extremity SSEPs resolved in one case. In one of the five cases involving thoracic injuries an abnormal lower-extremity SSEP resolved. Conclusions. The use of OFS treatment in patients with SCI is safe, reliable, and easy. Compared with the outcomes obtained in compliant NASCIS III plegic patients, the results of the present study indicate efficacy, and the FDA has given permission for enrollment of 10 additional patients.

Dural closure, cord approximation, and clot removal: enhancement of tissue sparing in a novel laceration spinal cord injury model

2004 ◽  
Vol 100 (4) ◽  
pp. 343-352 ◽  
Author(s):  
Yi Ping Zhang ◽  
Christopher Iannotti ◽  
Lisa B. E. Shields ◽  
Yingchun Han ◽  
Darlene A. Burke ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Connective Tissue ◽  
Scar Formation ◽  
Content Type ◽  
Dural Closure ◽  
Cord Injury ◽  
Group 2 ◽  
Fine Print ◽  
Group 1

Object. Laceration-induced spinal cord injury (SCI) results in the invasion of a connective tissue scar, progressive damage to the spinal cord due to complex secondary injury mechanisms, and axonal dieback of descending motor pathways. The authors propose that preparation of the spinal cord for repair strategies should include hematoma removal and dural closure, resulting in apposition of the severed ends of the spinal cord. Such procedures may reduce the size of the postinjury spinal cord cyst as well as limit scar formation. Methods. Using a novel device, the Vibraknife, the authors created a dorsal hemisection of the spinal cord at C-6 in the adult rat. In Group 1 (eight rats), the dura mater was repaired with apposition of the two stumps of the spinal cord to reduce the lesion gap. In Group 2 (10 rats), the dura was not closed and the two cord stumps were not approximated. All rats were killed at 4 weeks postinjury, and the spinal cords from each group were removed and examined using histological, stereological, and immunohistochemical methods. In Group 1 rats a significant reduction of the total lesion volume and connective tissue scar was observed compared with those in Group 2 (Student t-test, p < 0.05). Approximation of the stumps did not promote the regeneration of corticospinal tract fibers or sensory axons through the lesion site. Conclusions. Apposition of the severed ends of the spinal cord by dural closure reduces the lesion gap, cystic cavitation, and connective tissue scar formation. These outcomes may collectively reduce secondary tissue damage at the injury site and shorten the length of the lesion gap, which will facilitate transplantation-mediated axonal regeneration after laceration-induced SCI.

Effect of mexiletine on lipid peroxidation and early ultrastructural findings in experimental spinal cord injury

1999 ◽  
Vol 91 (2) ◽  
pp. 200-204 ◽  
Author(s):  
Erkan Kaptanoglu ◽  
Hakan H. Caner ◽  
H. Selçuk Sürücü ◽  
Filiz Akbiyik
Keyword(s):  
Spinal Cord ◽  
Lipid Peroxidation ◽  
Spinal Cord Injury ◽  
Sodium Succinate ◽  
Content Type ◽  
Methylprednisolone Sodium Succinate ◽  
Cord Injury ◽  
Group 3 ◽  
Ultrastructural Findings ◽  
Fine Print

Object. The purpose of this study was to investigate the effect of mexiletine on lipid peroxidation and on ultrastructural findings after induced spinal cord injury (SCI). The authors also compared the activity of mexiletine to that of the well-known antioxidant, methylprednisolone sodium succinate (MPSS). Methods. Wistar rats were divided into seven groups, (Groups 1–7). Those in Groups 1 and 2 were control animals that underwent laminectomy only, after which nontraumatized spinal cord samples were obtained immediately (Group 1) and 2 hours postsurgery (Group 2). Spinal cord injury was induced in all other groups, and cord samples were obtained at 2 hours postsurgery. The rats in Group 3 underwent SCI alone; those in Group 4 received 30 mg/kg of MPSS intraperitoneally immediately after trauma was induced; and those in Groups 5, 6, and 7 received 1, 10, and 50 mg/kg of mexiletine, respectively, by intraperitoneal injection immediately after trauma was induced. Compared with the levels in control animals, lipid peroxidation was significantly elevated in rats in Groups 3 and 5, but there were no statistical differences among those in Groups 1, 2, 4, 6 and 7 in this regard. Compared with the findings in rats in Group 3, ultrastructural damage post-SCI was minor in rats in Groups 4 and 5, and there was even less damage evident in rats in Group 7. Conclusions. Analysis of these findings showed that administration of 50 mg/kg mexiletine significantly decreased the level of lipid peroxidation and protected spinal cord ultrastructure following SCI.

A Phase I trial of naloxone treatment in acute spinal cord injury

1985 ◽  
Vol 63 (3) ◽  
pp. 390-397 ◽  
Author(s):  
Eugene S. Flamm ◽  
Wise Young ◽  
William F. Collins ◽  
Joseph Piepmeier ◽  
Guy L. Clifton ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Phase I ◽  
Phase I Trial ◽  
Loading Dose ◽  
Content Type ◽  
Cord Injury ◽  
Group 2 ◽  
Time Of Admission ◽  
Fine Print

✓ Results of a Phase I trial of the opiate antagonist naloxone for treatment of patients with acute spinal cord injury are reported. Naloxone was administered in doses ranging from 5 to 200 mg/sq m (0.14 to 5.4 mg/kg) for up to 48 hours. The patients ranged in age from 16 to 79 years (mean 37 years). Twenty patients received naloxone as a loading dose of 5 to 50 mg/sq m (0.14 to 1.43 mg/kg), followed by a maintenance dose of 20% of the loading dose given as a continuous infusion hourly for 47 hours (Group 1). Nine patients received a loading dose of 100 to 200 mg/sq m (2.7 to 5.4 mg/kg) and a maintenance dose of 75% of the initial dose hourly for 23 hours (Group 2). These higher doses (2.7 to 5.4 mg/kg) have been found to be effective in experimental spinal cord injury. Neurological examinations were performed and somatosensory evoked potentials (SEP's) were obtained as soon after admission as possible and again 1, 2, 3, and 7 days, 3 weeks, and 6 weeks to 6 months after admission. The 20 Group 1 patients who received 1.43 mg/kg or less of naloxone showed no improvement in neurological status or SEP's. All but three (15%) of these patients had a complete neurological deficit at the time of admission. Treatment was begun an average of 12.9 hours after injury. Among the nine Group 2 patients treated with 2.7 mg/kg or more, there were five patients (56%) with incomplete deficits. This group received naloxone an average of 6.6 hours after admission. Two of the five Group 2 patients with incomplete lesions showed improvement in their neurological condition and/or SEP's within 36 hours of receiving the drug. One of the four Group 2 patients with a complete lesion at the time of admission was able to localize pressure sensation in his legs 36 hours after completion of the drug infusion. Four Group 2 patients (two with complete and two with incomplete lesions) have shown improvement in their SEP's, suggesting recovery of SEP's in a dose-related fashion. Four patients experienced increased pain after administration of the loading dose and during the maintenance infusion; in only one patient was this severe enough to require discontinuation of the drug. Of the 29 patients treated with naloxone, four died within 6 weeks of admission, for a mortality rate of 13.8%. This study demonstrates that, in spinal cord-injured patients, naloxone given as an intravenous loading dose of 200 mg/sq m, followed by a continuous infusion of up to 150 mg/sq m/hr for 23 hours, has minimal side effects. The observed improvement in the clinical examination and SEP's at the higher doses, while not statistically verified in this Phase I trial, is encouraging.

Split spinal cord malformations in children

1998 ◽  
Vol 88 (1) ◽  
pp. 57-65 ◽  
Author(s):  
Yusuf Ersşahin ◽  
Saffet Mutluer ◽  
Sevgül Kocaman ◽  
Eren Demirtasş
Keyword(s):  
Spinal Cord ◽  
Neurological Deficits ◽  
Single Type ◽  
Type I ◽  
Type Ii ◽  
Content Type ◽  
Spinal Lesion ◽  
The Mean ◽  
Fine Print

Object. The authors reviewed and analyzed information on 74 patients with split spinal cord malformations (SSCMs) treated between January 1, 1980 and December 31, 1996 at their institution with the aim of defining and classifying the malformations according to the method of Pang, et al. Methods. Computerized tomography myelography was superior to other radiological tools in defining the type of SSCM. There were 46 girls (62%) and 28 boys (38%) ranging in age from less than 1 day to 12 years (mean 33.08 months). The mean age (43.2 months) of the patients who exhibited neurological deficits and orthopedic deformities was significantly older than those (8.2 months) without deficits (p = 0.003). Fifty-two patients had a single Type I and 18 patients a single Type II SSCM; four patients had composite SSCMs. Sixty-two patients had at least one associated spinal lesion that could lead to spinal cord tethering. After surgery, the majority of the patients remained stable and clinical improvement was observed in 18 patients. Conclusions. The classification of SSCMs proposed by Pang, et al., will eliminate the current chaos in terminology. In all SSCMs, either a rigid or a fibrous septum was found to transfix the spinal cord. There was at least one unrelated lesion that caused tethering of the spinal cord in 85% of the patients. The risk of neurological deficits resulting from SSCMs increases with the age of the patient; therefore, all patients should be surgically treated when diagnosed, especially before the development of orthopedic and neurological manifestations.

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.

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