Effects of epidural hypothermic saline infusion on locomotor outcome and tissue preservation after moderate thoracic spinal cord contusion in rats

2005 ◽  
Vol 2 (3) ◽  
pp. 308-318 ◽  
Author(s):  
Carlos E. Casas ◽  
Loren P. Herrera ◽  
Chad Prusmack ◽  
Gladys Ruenes ◽  
Alexander Marcillo ◽  
...  

Object. Regionally delivered hypothermia has advantages over systemic hypothermia for clinical application following spinal cord injury (SCI). The effects of local hypothermia on tissue sparing, neuronal preservation, and locomotor outcome were studied in a moderate thoracic spinal cord contusion model. Methods. Rats were randomized to four treatment groups and data were collected and analyzed in a blinded fashion. Chilled saline was perfused into the epidural space 30 minutes postcontusion to achieve the following epidural temperatures: 24 ± 2.3°C (16 rats), 30 ± 2.4°C (13 rats), and 35 ± 0.9°C (13 rats). Hypothermia was continued for 3 hours when a 45-minute period of rewarming was instituted. In a fourth group a moderate contusion only was induced in 14 animals. Rectal (core) and T9–10 (epidural) temperatures were measured continuously. Locomotor testing, using the Basso-Beattie-Bresnahan (Ba-Be-Br) scale, was performed for 6 weeks, and rats were videotaped for subsequent analysis. The lesion/preserved tissue ratio was calculated throughout the entire lesion cavity and the total lesion, spinal cord, and spared tissue volumes were determined. The rostral and caudal extent of gray matter loss was also measured. At 6 weeks locomotor recovery was similar in all groups (mean Ba-Be-Br Scale scores 14.88 ± 3.71, 14.83 ± 2.81, 14.50 ± 2.24, and 14.07 ± 2.39 [p = 0.77] for all four groups, respectively). No significant differences in spared tissue volumes were found when control and treatment groups were compared, but gray matter preservation was reduced in the infusion-treated groups. Conclusions. Regional cooling applied 30 minutes after a moderate contusive SCI was not beneficial in terms of tissue sparing, neuronal preservation, or locomotor outcome. This method of cooling may reduce blood flow in the injured spinal cord and exacerbate secondary injury.

1997 ◽  
Vol 87 (2) ◽  
pp. 239-246 ◽  
Author(s):  
Fernando L. Vale ◽  
Jennifer Burns ◽  
Amie B. Jackson ◽  
Mark N. Hadley

✓ The optimal management of acute spinal cord injuries remains to be defined. The authors prospectively applied resuscitation principles of volume expansion and blood pressure maintenance to 77 patients who presented with acute neurological deficits as a result of spinal cord injuries occurring from C-1 through T-12 in an effort to maintain spinal cord blood flow and prevent secondary injury. According to the Intensive Care Unit protocol, all patients were managed by using Swan—Ganz and arterial blood pressure catheters and were treated with immobilization and fracture reduction as indicated. Intravenous fluids, colloid, and vasopressors were administered as necessary to maintain mean arterial blood pressure above 85 mm Hg. Surgery was performed for decompression and stabilization, and fusion in selected cases. Sixty-four patients have been followed at least 12 months postinjury by means of detailed neurological assessments and functional ability evaluations. Sixty percent of patients with complete cervical spinal cord injuries improved at least one Frankel or American Spinal Injury Association (ASIA) grade at the last follow-up review. Thirty percent regained the ability to walk and 20% had return of bladder function 1 year postinjury. Thirty-three percent of the patients with complete thoracic spinal cord injuries improved at least one Frankel or ASIA grade. Approximately 10% of the patients regained the ability to walk and had return of bladder function. As of the 12-month follow-up review, 92% of patients demonstrated clinical improvement after sustaining incomplete cervical spinal cord injuries compared to their initial neurological status. Ninety-two percent regained the ability to walk and 88% regained bladder function. Eighty-eight percent of patients with incomplete thoracic spinal cord injuries demonstrated significant improvements in neurological function 1 year postinjury. Eighty-eight percent were able to walk and 63% had return of bladder function. The authors conclude that the enhanced neurological outcome that was observed in patients after spinal cord injury in this study was in addition to, and/or distinct from, any potential benefit provided by surgery. Early and aggressive medical management (volume resuscitation and blood pressure augmentation) of patients with acute spinal cord injuries optimizes the potential for neurological recovery after sustaining trauma.


2001 ◽  
Vol 94 (2) ◽  
pp. 257-264 ◽  
Author(s):  
Mercedes Zurita ◽  
Jesús Vaquero ◽  
Isabel Zurita

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.


1987 ◽  
Vol 66 (3) ◽  
pp. 447-452 ◽  
Author(s):  
Yutaka Naka ◽  
Toru Itakura ◽  
Kunio Nakai ◽  
Kazuo Nakakita ◽  
Harumichi Imai ◽  
...  

✓ The microangioarchitecture of corrosion casts of the cat spinal cord was studied by scanning electron microscopy. On the ventral surface of the spinal cord, the anterior spinal artery and the anterior spinal vein ran parallel along the anterior median fissure. Many central arteries branching from the anterior spinal artery coursed in a wavelike manner in the anterior median fissure. The number of central arteries was lowest in the thoracic spinal cord. Central arteries at some spinal cord levels revealed well-developed anastomoses with other central arteries in the anterior median fissure. These well-developed anastomotic central arteries were frequently observed in the thoracic spinal cord, in which the number of central arteries was lowest. On the dorsal surface of the spinal cord, the posterior spinal vein ran longitudinally at the midline and was drained by circumferential veins and posterior central veins. This vein formed a characteristic anastomotic plexus. Small arterioles (20 µm in diameter) in the spinal parenchyma revealed a ring-like compression at the branching site.


1992 ◽  
Vol 76 (2) ◽  
pp. 280-291 ◽  
Author(s):  
R. John Hurlbert ◽  
Charles H. Tator ◽  
Michael G. Fehlings ◽  
Greg Niznik ◽  
R. Dean Linden

✓ Although the assessment of spinal cord function by electrophysiological techniques has become important in both clinical and research environments, current monitoring methods do not completely evaluate all tracts in the spinal cord. Somatosensory and motor evoked potentials primarily reflect dorsal column and pyramidal tract integrity, respectively, but do not directly assess the status of the ventral funiculus. The present study was undertaken to evaluate the use of evoked potentials, elicited by direct cerebellar stimulation, in monitoring the ventral component of the rodent spinal cord. Twenty-nine rats underwent epidural anodal stimulation directly over the cerebellar cortex, with recording of evoked responses from the lower thoracic spinal cord, both sciatic nerves, and/or both gastrocnemius muscles. Stimulation parameters were varied to establish normative characteristics. The pathways conducting these “posterior fossa evoked potentials” were determined after creation of various lesions of the cervical spinal cord. The evoked potential recorded from the thoracic spinal cord consisted of five positive (P1 to P5) and five negative (N1 to N5) peaks. The average conduction velocity (± standard deviation) of the earliest wave (P1) was 53 ± 4 m/sec, with a latency of 1.24 ± 0.10 msec. The other components followed within 4 msec from stimulus onset. Unilateral cerebellar stimulation resulted in bilateral sciatic nerve and gastrocnemius muscle responses; there were no significant differences (p > 0.05) in the thresholds, amplitudes, or latencies of these responses elicited by right- versus left-sided stimulation. Recordings performed following creation of selective lesions of the cervical cord indicated that the thoracic response was carried primarily in the ventral funiculus while the sciatic and gastrocnemius responses were mediated through the dorsal half of the spinal cord. It is concluded that the posterior fossa evoked potential has research value as a method of monitoring pathways within the ventral spinal cord of the rat, and should be useful in the study of spinal cord injury.


1982 ◽  
Vol 56 (1) ◽  
pp. 143-144
Author(s):  
Jose Berciano ◽  
Jaime Gutierrez ◽  
Mariano Rebollo ◽  
Guillermo Dierssen

✓ A case of thoracic spinal cord ependymoma presenting with ejaculatory failure is described. This mode of onset has not previously been reported in patients with thoracic intraspinal tumors.


1989 ◽  
Vol 71 (3) ◽  
pp. 403-416 ◽  
Author(s):  
Michael G. Fehlings ◽  
Charles H. Tator ◽  
R. Dean Linden

✓ There is evidence that posttraumatic ischemia is important in the pathogenesis of acute spinal cord injury (SCI). In the present study spinal cord blood flow (SCBF), measured by the hydrogen clearance technique, and motor and somatosensory evoked potentials (MEP and SSEP) were recorded to evaluate whether the administration of nimodipine and dextran 40, alone or in combination, could increase posttraumatic SCBF and improve axonal function in the cord after acute SCI. Thirty rats received a 53-gm clip compression injury on the cord at T-1 and were then randomly and blindly allocated to one of six treatment groups (five rats in each). Each group was given an intravenous infusion of one of the following over 1 hour, commencing 1 hour after SCI: placebo and saline; placebo and dextran 40; nimodipine 0.02 mg/kg and saline; nimodipine 0.02 mg/kg and dextran 40; nimodipine 0.05 mg/kg and saline; and nimodipine 0.05 mg/kg and dextran 40. The preinjury physiological parameters, including the SCBF at T-1 (mean ± standard error of the mean: 56.84 ± 4.51 ml/100 gm/min), were not significantly different (p > 0.05) among the treatment groups. Following SCI, there was a significant decrease in the SCBF at T-1 (24.55 ± 2.99 ml/100 gm/min; p < 0.0001) as well as significant changes in the MEP recorded from the spinal cord (MEP-C) (p < 0.0001), the MEP recorded from the sciatic nerve (MEP-N) (p < 0.0001), and the SSEP (p < 0.002). Only the combination of nimodipine 0.02 mg/kg and dextran 40 increased the SCBF at T-1 (43.69 ± 6.09 ml/100 gm/min; p < 0.003) and improved the MEP-C (p < 0.0001), MEP-N (p < 0.04), and SSEP (p < 0.002) following SCI. With this combination, the changes in SCBF were significantly related to improvement in axonal function in the motor tracts (p < 0.0001) and somatosensory tracts (p < 0.0001) of the cord. This study provides quantitative evidence that an increase in posttraumatic SCBF can significantly improve the function of injured spinal cord axons, and strongly implicates posttraumatic ischemia in the pathogenesis of acute SCI.


2020 ◽  
Vol 21 (23) ◽  
pp. 8997
Author(s):  
Gyu-Tae Kim ◽  
Adrian S. Siregar ◽  
Eun-Jin Kim ◽  
Eun-Shin Lee ◽  
Marie Merci Nyiramana ◽  
...  

TWIK (tandem-pore domain weak inward rectifying K+)-related spinal cord K+ channel (TRESK), a member of the two-pore domain K+ channel family, is abundantly expressed in dorsal root ganglion (DRG) neurons. It is well documented that TRESK expression is changed in several models of peripheral nerve injury, resulting in a shift in sensory neuron excitability. However, the role of TRESK in the model of spinal cord injury (SCI) has not been fully understood. This study investigates the role of TRESK in a thoracic spinal cord contusion model, and in transgenic mice overexpressed with the TRESK gene (TGTRESK). Immunostaining analysis showed that TRESK was expressed in the dorsal and ventral neurons of the spinal cord. The TRESK expression was increased by SCI in both dorsal and ventral neurons. TRESK mRNA expression was upregulated in the spinal cord and DRG isolated from the ninth thoracic (T9) spinal cord contusion rats. The expression was significantly upregulated in the spinal cord below the injury site at acute time points (6, 24, and 48 h) after SCI (p < 0.05). In addition, TRESK expression was markedly increased in DRGs below and adjacent to the injury site. TRESK was expressed in inflammatory cells. In addition, the number and fluorescence intensity of TRESK-positive neurons increased in the dorsal and ventral horns of the spinal cord after SCI. TGTRESK SCI mice showed faster paralysis recovery and higher mechanical threshold compared to wild-type (WT)-SCI mice. TGTRESK mice showed lower TNF-α concentrations in the blood than WT mice. In addition, IL-1β concentration and apoptotic signals in the caudal spinal cord and DRG were significantly decreased in TGTRESK SCI mice compared to WT-SCI mice (p < 0.05). These results indicate that TRESK upregulated following SCI contributes to the recovery of paralysis and mechanical pain threshold by suppressing the excitability of motor and sensory neurons and inflammatory and apoptotic processes.


1970 ◽  
Vol 33 (5) ◽  
pp. 554-563 ◽  
Author(s):  
David L. Kelly ◽  
Kenneth R. L. Lassiter ◽  
John A. Calogero ◽  
Eben Alexander

✓ A controlled series of adult mongrel dogs were rendered paraplegic by traumatizing the thoracic spinal cord. Those animals treated with local hypothermia, whether immediately or after a delay, recovered to a significantly greater degree than the untreated group. Spinal cord pO2 studies revealed a marked fall in the pO2 at the area of maximal injury over a 30-min period. The severe hypoxia lasted at least 7 hours. Pathological studies showed the varying degrees of injury produced. It is postulated that local hypothermia may be effective in altering the clinical recovery by decreasing the tissue metabolism at the site of injury.


1979 ◽  
Vol 50 (2) ◽  
pp. 198-206 ◽  
Author(s):  
Howard J. Senter ◽  
Joan L. Venes

✓ Blood flow in the dorsolateral funiculus of the cat thoracic spinal cord was studied after severe experimental cord injury, using a modification of the hydrogen clearance technique. Autoregulation was intact during the initial 60 to 90 minutes after cord injury, but was then lost coincident with the onset of ischemia. The data suggest that the ischemic response to spinal cord injury is mediated both by the loss of autoregulation and by relative vasoconstriction of the resistance vessels. Therapeutic intervention aimed at maintaining perfusion during the early posttraumatic period may prove of value in reversing or limiting some elements of dysfunction due to the secondary injury of ischemia.


2017 ◽  
Vol 26 (1) ◽  
pp. 62-75 ◽  
Author(s):  
Devesh Jalan ◽  
Neginder Saini ◽  
Mohammad Zaidi ◽  
Alexandra Pallottie ◽  
Stella Elkabes ◽  
...  

OBJECTIVE In acute traumatic brain injury, decompressive craniectomy is a common treatment that involves the removal of bone from the cranium to relieve intracranial pressure. The present study investigated whether neurological function following a severe spinal cord injury improves after utilizing either a durotomy to decompress the intradural space and/or a duraplasty to maintain proper flow of cerebrospinal fluid. METHODS Sixty-four adult female rats (n = 64) were randomly assigned to receive either a 3- or 5-level decompressive laminectomy (Groups A and B), laminectomy + durotomy (Groups C and D), or laminectomy + duraplasty with graft (Group E and F) at 24 hours following a severe thoracic contusion injury (200 kilodynes). Duraplasty involved the use of DuraSeal, a hydrogel dural sealant. Uninjured and injured control groups were included (Groups G, H). Hindlimb locomotor function was assessed by open field locomotor testing (BBB) and CatWalk gait analysis at 35 days postinjury. Bladder function was analyzed and bladder wall thickness was assessed histologically. At 35 days postinjury, mechanical and thermal allodynia were assessed by the Von Frey hair filament and hotplate paw withdrawal tests, respectively. Thereafter, the spinal cords were dissected, examined for gross anomalies at the injury site, and harvested for histological analyses to assess lesion volumes and white matter sparing. ANOVA was used for statistical analyses. RESULTS There was no significant improvement in motor function recovery in any treatment groups compared with injured controls. CatWalk gait analysis indicated a significant decrease in interlimb coordination in Groups B, C, and D (p < 0.05) and swing speed in Groups A, B, and D. Increased mechanical pain sensitivity was observed in Groups A, C, and F (p < 0.05). Rats in Group C also developed thermal pain hypersensitivity. Examination of spinal cords demonstrated increased lesion volumes in Groups C and F and increased white matter sparing in Group E (p < 0.05). The return of bladder automaticity was similar in all groups. Examination of the injury site during tissue harvest revealed that, in some instances, expansion of the hydrogel dural sealant caused compression of the spinal cord. CONCLUSIONS Surgical decompression provided no benefit in terms of neurological improvement in the setting of a severe thoracic spinal cord contusion injury in rats at 24 hours postinjury. Decompressive laminectomy and durotomy did not improve motor function recovery, and rats in both of these treatment modalities developed neuropathic pain. Performing a durotomy also led to increased lesion volumes. Placement of DuraSeal was shown to cause compression in some rats in the duraplasty treatment groups. Decompressive duraplasty of 3 levels does not affect functional outcomes after injury but did increase white matter sparing. Decompressive duraplasty of 5 levels led to neuropathic pain development and increased lesion volumes. Further comparison of dural repair techniques is necessary.


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