Beneficial effects of modest systemic hypothermia on locomotor function and histopathological damage following contusion-induced spinal cord injury in rats

2000 ◽  
Vol 93 (1) ◽  
pp. 85-93 ◽  
Author(s):  
Chen Guang Yu ◽  
Omar Jimenez ◽  
Alexander E. Marcillo ◽  
Brian Weider ◽  
Kurt Bangerter ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Content Type ◽  
Locomotor Function ◽  
Beneficial Effects ◽  
Cord Injury ◽  
Systemic Hypothermia ◽  
C 30 ◽  
Fine Print

Object. Local spinal cord cooling (LSCC) is associated with beneficial effects when applied following ischemic or traumatic spinal cord injury (SCI). However, the clinical application of LSCC is associated with many technical difficulties such as the requirement of special cooling devices, emergency surgery, and complicated postoperative management. If hypothermia is to be considered for future application in the treatment of SCI, alternative approaches must be developed. The objectives of the present study were to evaluate 1) the relationship between systemic and epidural temperature after SCI; 2) the effects of modest systemic hypothermia on histopathological damage at 7 and 44 days post-SCI; and 3) the effects of modest systemic hypothermia on locomotor outcome at 44 days post-SCI. Methods. A spinal cord contusion (12.5 mm at T-10) was produced in adult rats that had been randomly divided into two groups. Group 1 rats (seven in Experiment 1; 12 in Experiment 2) received hypothermic treatment (epidural temperature 32–33°C) 30 minutes postinjury for 4 hours; Group 2 rats (nine in Experiment 1; eight in Experiment 2) received normothermic treatment (epidural temperature 37°C) 30 minutes postinjury for 4 hours. Blood pressure, blood gas levels, and temperatures (epidural and rectal) were monitored throughout the 4-hour treatment period. Twice weekly assessment of locomotor function was performed over a 6-week survival period by using the Basso-Beattie-Bresnahan locomotor rating scale. Seven (Experiment 1) and 44 (Experiment 2) days after injury, animals were killed, perfused, and their spinal cords were serially sectioned. The area of tissue damage was quantitatively analyzed from 16 longitudinal sections selected from the central core of the spinal cord. Conclusions. The results showed that 1) modest changes in the epidural temperature of the spinal cord can be produced using systemic hypothermia; 2) modest systemic hypothermia (32–33°C) significantly protects against locomotor deficits following traumatic SCI; and 3) modest systemic hypothermia (32–33°C) reduces the area of tissue damage at both 7 and 44 days postinjury. Although additional research is needed to study the therapeutic window and long-term benefits of systemic hypothermia, these data support the possible use of modest systemic hypothermia in the treatment of acute SCI.

Evaluation of time-dependent spread of tissue damage in experimental spinal cord injury by killed-end evoked potential: effect of high-dose methylprednisolone

2003 ◽  
Vol 98 (1) ◽  
pp. 56-62 ◽  
Author(s):  
Chikashi Fukaya ◽  
Yoichi Katayama ◽  
Masahiko Kasai ◽  
Jun Kurihara ◽  
Sadahiro Maejima ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Conduction Block ◽  
Time Dependent ◽  
High Dose ◽  
Injury Site ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

Object. Histopathological studies on spinal cord injury (SCI) have demonstrated time-dependent spread of tissue damage during the initial several hours postinjury. When the long tract within the spinal cord is stimulated, a large monophasic positivity occurs at the injury site. This type of potential, termed the killed-end evoked potential (KEEP), indicates that a nerve impulse approaches but does not pass beyond the injury site. The authors tested the hypothesis that the damage spread can be evaluated as a progressive shift of the KEEP on a real-time basis. The effect of high-dose methylprednisolone sodium succinate (MPSS) on the spread of tissue damage was also examined by this methodology. Methods. The KEEP was recorded using an electrode array placed on the spinal cord at the T-10 level in cats. This electrode array consisted of multiple 0.2-mm-diameter electrodes, each separated by 0.5 mm. Spinal cord injury was induced using a vascular clip (65 g pinching pressure for 30 seconds). The midline posterior surface of the spinal cord was stimulated bipolarly at the C-7 level by applying a single pulse at supramaximal intensity. During the initial period of 6 hours postinjury, the localization of the largest KEEP shifted progressively up to 2.5 mm rostral from the injury site. The amplitude of the KEEP recorded at the injury site decreased to 55 to 70% and became slightly shortened in latency as the localization of the largest KEEP shifted rostrally. These findings imply that the injury site KEEP represents the volume-conducted potential of the largest KEEP at the site of the conduction block. It moved away from the injury site in association with the damage spread, and this was confirmed histopathologically. A decrease in amplitude of KEEP at the injury site appeared to be the most sensitive measure of the damage spread, because the amplitude of the volume-conducted KEEP is inversely proportional to the square of the distance between the recording site and site of conduction block. Administered immediately after SCI, MPSS clearly inhibited these events, especially within 30 minutes postinjury. Conclusions. The KEEP enables sequential evaluation to be made of the time-dependent spread of tissue damage in SCI in the same animal. It is, therefore, useful for detecting the effect of therapeutic interventions and for determining the therapeutic time window. The efficiency of MPSS to inhibit the spread of damaged tissue appeared to be maximized when it was administered within the initial 30-minute period postinjury.

A simple and reliable behavioral analysis of locomotor function after spinal cord injury in mice

2002 ◽  
Vol 97 (1) ◽  
pp. 142-147 ◽  
Author(s):  
Yuji Mikami ◽  
Masahiro Toda ◽  
Masahiko Watanabe ◽  
Masaya Nakamura ◽  
Yoshiaki Toyama ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Rating Scale ◽  
Animal Movement ◽  
Vertical Movement ◽  
Behavioral Analysis ◽  
Content Type ◽  
Locomotor Function ◽  
Cord Injury ◽  
Fine Print

✓ To establish a simple and reliable method to assess the behavioral function after spinal cord injury (SCI) in mice, the authors used an automated animal movement analysis system, SCANET. Two different SCI lesions were created in adult female BALB/c and C57BL/6 mice by transecting both the posterior columns and the left lateral and anterior funiculi or only the left lateral and anterior funiculi at T-8. Control mice underwent laminectomy only. The SCANET system consists of a cage equipped with two crossing sensor frames arranged at different heights, by which small (M1) and large (M2) horizontal movements and the vertical movement involved in rearing (RG) can be monitored. The authors assessed locomotor function by determining the M1, M2, and RG scores; to this end, they used the SCANET system and a previously established behavior test, the 21-point open-field Basso-Beattie-Bresnahan (BBB) Locomotor Rating Scale. The results indicated that the RG scores were significantly and consistently different between the spinal cord—injured and control mice, irrespective of the mouse strain or injury model, but that M1 and M2 scores were not. Moreover, there was a statistically positive correlation between the RG score and the BBB Scale score. For the assessment of locomotor function after SCI, use of the SCANET sytem in behavioral analysis is simple and the method is highly reproducible. The analysis of vertical movement is useful for assessing the recovery of limb function in mice following thoracic hemisection.

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.

Genetic Ablation of Transcription Repressor Bach1 Reduces Neural Tissue Damage and Improves Locomotor Function after Spinal Cord Injury in Mice

2009 ◽  
Vol 26 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Haruo Kanno ◽  
Hiroshi Ozawa ◽  
Yoshihiro Dohi ◽  
Akira Sekiguchi ◽  
Kazuhiko Igarashi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Tissue Damage ◽  
Neural Tissue ◽  
Locomotor Function ◽  
Genetic Ablation ◽  
Cord Injury

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.

Bladder function after incomplete spinal cord injury in mice: quantifiable outcomes associated with bladder function and efficiency of dehydroepiandrosterone as a therapeutic adjunct

2004 ◽  
Vol 100 (1) ◽  
pp. 56-61
Author(s):  
Pierre-Yves Mure ◽  
Mark Galdo ◽  
Nathalie Compagnone
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Mouse Model ◽  
Collagen Type ◽  
Neurological Recovery ◽  
Bladder Function ◽  
Type I ◽  
Content Type ◽  
Cord Injury ◽  
Fine Print

Object. The authors conducted a study to establish outcomes associated with bladder function in a mouse model of spinal cord injury (SCI) and to assess the sensitivity of these outcomes in determining the efficacy of pharmacological treatments. Methods. A mouse model of moderate contusive SCI was used. Outcome parameters included physiological, behavioral, and morphological measurements. To test the sensitivity of these outcomes, the authors used a dehydroepiandrosterone (DHEA) treatment that they had previously shown to promote neurological recovery effectively after SCI. A behavioral scale was used to identify the day at which autonomic function of the bladder was recovered. The reduction in the daily volume of urine during the period of functional recovery paralleled this scale. They then determined the day postinjury at which the functional differences between the vehicle- and DHEA-treated mice exhibited the maximal amplitude. Changes were measured in the composition of the extracellular matrix relative to collagen expression in the layer muscularis of the detrusor at this time point. They found that SCI increases the ratio of collagen type III to collagen type I in the detrusor. Moreover, in the DHEA-treated group, this ratio was similar to that demonstrated in sham-operated mice, establishing the sensitivity of this outcome to assess therapeutic benefits to the bladder function. They next examined the relationship between measurements of neurological recovery and controlled voiding by using cluster analysis. Conclusions. The authors found that early recovery of controlled voiding is predictive of motor recovery.

Immediate effects of spinal cord stimulation in spinal spasticity

1985 ◽  
Vol 62 (4) ◽  
pp. 558-562 ◽  
Author(s):  
Giancarlo Barolat-Romana ◽  
Joel B. Myklebust ◽  
David C. Hemmy ◽  
Barbara Myklebust ◽  
William Wenninger
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Spinal Cord Stimulation ◽  
Content Type ◽  
Clinical Observations ◽  
Cord Injury ◽  
Epidural Spinal Cord Stimulation ◽  
Stimulation System ◽  
Fine Print

✓ Six patients with intractable spasms after spinal cord injury underwent implantation of an epidural spinal cord stimulation system. All the patients experienced good relief postoperatively. In three patients spinal cord stimulation consistently produced immediate inhibition of the spasms. This was evident within less than 1 minute of stimulation. Conversely, the spasms reappeared within less than 1 minute after cessation of the stimulation. The clinical observations were confirmed by polygraphic electromyographic recordings.

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