The effect of acute spinal cord compression injury on thyroid function in the rat

The effect of acute spinal cord injury on thyroid function was studied in rats subjected to severe spinal cord compression at T1. Serum thyroxine (T4), effective thyroxine index (ETI), and thyroid stimulating hormone (TSH) were measured at 1 and 100 minutes and at one, three, and seven days after laminectomy and spinal cord injury. Control animals were subjected to laminectomy only. T4 was decreased at 1 minute after laminectomy with or without spinal cord injury, though the animals with cord injury had a much more profound reduction. The effects on TSH at 1 minute were dramatically different: laminectomy alone caused an elevation of TSH, while spinal cord injury produced a marked decline. At the later time intervals both groups showed gradual normalization of T4 and TSH levels, and at seven days there were no significant differences between the groups. Thus, acute spinal cord compression injury produced a major alteration in thyroid function during the acute phase.     

Effects of multi-dose methylprednisolone sodium succinate administration on injured cat spinal cord neurofilament degradation and energy metabolism

Thirty minutes after experimental spinal cord contusion (500 gm-cm) injury, cats were treated with an initial intravenous dose of either vehicle (V) or 30 mg/kg of Solu-Medrol sterile powder (methylprednisolone sodium succinate; MPSS). Two hours later, cats received a second intravenous injection of either V or 15 mg/kg MPSS, giving three treatment groups: V/V; MPSS/V; MPSS/MPSS. At 4 1/2 hours following injury of the cat lumbar spinal cord, the gray and white matter neurofilament protein content was reduced by over 70% within the injured segment of V/V-treated animals. The three major cat spinal cord neurofilament protein subunits of 200,000, 152,000, and 76,000 daltons were reduced in parallel by the injury. Treatment of cats with a single 30-mg/kg dose of MPSS (MPSS/V) provided a clear, although not significant, protection against neurofilament degradation compared with V/V-treated cats when measured at 4 1/2 hours after injury. The lactic acid content of the injured spinal cord segment at 4 1/2 hours after injury was significantly elevated in both V/V- and MPSS/V-treated cats, while the adenosine triphosphate (ATP) content, total adenylates, and energy charge were significantly reduced. The administration of a second intravenous 15-mg/kg dose of MPSS 2 hours after the initial 30-mg/kg dose (MPSS/MPSS) provided complete (p less than 0.01) preservation of neurofilaments within the injured spinal cord segment measured at 4 1/2 hours after injury. The levels of lactate, ATP, total adenylates, and tissue energy charge in MPSS/MPSS-treated cats were not different from those of uninjured spinal cords following laminectomy. The (Na+ + K+)-ATPase activity in the injured spinal segment was enhanced, although highly variable, in MPSS/V-treated animals. On the other hand, spinal cord enzyme activity was significantly and consistently elevated in the MPSS/MPSS-treated group. The results demonstrate that a 30-mg/kg dose of MPSS followed at 2 hours by a 15-mg/kg dose provides significantly better protection against injury-induced ischemia and Ca++-dependent neurofilament degradation than a single 30-mg/kg dose. These findings are in agreement with the spinal cord tissue pharmacokinetics and time-action characteristics of methylprednisolone observed in earlier studies.     

Chronic and acute compressive spinal cord lesions in dogs due to intervertebral disc herniation are associated with elevation in lumbar cerebrospinal fluid glutamate concentration

Acute injury to the central nervous system initiates a series of biochemical events that cause secondary tissue damage. The accumulation of excessive concentrations of glutamate in the extracellular space causes excitotoxic damage, and is incriminated as a mediator of this secondary tissue damage. The aim of this study was to measure the concentration of glutamate in cerebrospinal fluid (CSF) obtained from the cerebellomedullary cistern and lumbar subarachnoid space in dogs with acute and chronic compressive injuries of the cervical and thoracolumbar spinal cord, and to correlate the glutamate concentration with injury severity. The results demonstrate that focal injuries of the spinal cord do not affect the glutamate concentration in CSF taken from the cerebellomedullary cistern. However, dogs with severe, acute thoracolumbar disc herniations have two- to 10-fold increases in glutamate concentration in their lumbar CSF at intervals of >12 h after injury. Moreover, the severity of their clinical signs is directly related to the glutamate concentration. Dogs with chronic compressive thoracolumbar lesions have a two-fold elevation of CSF glutamate concentration, suggesting that excitotoxicity may also be a component of chronic spinal cord compression.     

高渗盐水治疗脊髓急性压迫损伤的实验研究

目的观察高渗盐水对脊髓损伤的治疗作用,并探讨其作用机制.方法 36只SD大鼠造成T10节段脊髓急性压迫损伤后,随机分为三组:高渗盐水治疗组、生理盐水治疗组及对照组,每组观察损伤后1、4周两时间段;评价动物神经功能,观察各时间段脊髓病理改变,计算脊髓残留组织保留率.结果①高渗盐水治疗组动物神经功能恢复更快、更完全,与生理盐水组及对照组相比差异有显著意义(P＜0.05);②损伤后1周,高渗盐水治疗组脊髓组织炎症反应、水肿明显减轻;③损伤后4周,高渗盐水治疗组脊髓残留组织保留率显著增加,与其它两组相比差异有显著性意义(P＜0.01).结论高渗盐水能减轻脊髓组织病理改变,促进神经功能恢复;减轻损伤后脊髓组织的炎症反应及水肿是其作用机制之一.     

Lactate and pyruvate metabolism in injured cat spinal cord before and after a single large intravenous dose of methylprednisolone

The lactate content and the lactate/pyruvate ratio of the acutely traumatized cat spinal cord have been studied and were found to rise rapidly following a 400 gm-cm injury. Lactate levels rose nearly twofold within 5 minutes after injury, peaked at 2 hours after injury, and remained significantly elevated for at least 8 hours compared to an adjacent uninjured segment of traumatized cord. Pyruvate levels, on the other hand, fell acutely in the injured section of cord during the 1st hour after injury then rose slowly over an 8-hour period. The changes in tissue lactate and pyruvate metabolism in the spinal cord following injury are consistent with a marked injury-induced reduction in blood flow. The elevation in lactate and the fall in pyruvate levels observed at 1 hour after injury were completely prevented by the intravenous administration of a single 30-mg/kg dose of methylprednisolone sodium succinate at 30 minutes after injury. Lower or higher doses of methylprednisolone were far less effective. The effects of the 30-mg/kg dose of methylprednisolone on tissue lactate content were associated with high tissue levels of the glucocorticoid and were short-lived, paralleling the accumulation and elimination pattern of steroid from the injured tissue. The results suggest that, in addition to other reported beneficial actions of large intravenous doses (30 mg/kg) of methylprednisolone on the injured cord, the glucocorticoid may also improve blood flow to the injured segment as has been suggested by others. The use of high glucocorticoid doses, early therapy initiation, and rigorous maintenance dosing is discussed.     

血管内皮生长因子在大鼠持续性脊髓压迫伤中的表达

目的研究血管内皮生长因子(VEGF)在实验大鼠持续性脊髓压迫伤中的表达变化,并探讨其在脊髓压迫伤中的作用和意义。方法健康封闭群W istar大鼠60只,体重280~300 g,采用平头塑料螺钉后路压迫复制大鼠持续性脊髓压迫伤的动物模型(脊髓50%压迫)。以改良Tarlov评分、BBB-21点评分及斜板实验评价其后肢运动功能;应用免疫组织化学和原位杂交技术,检测脊髓组织在持续性压迫适应中不同时段VEGF-mRNA和蛋白的表达,并结合计算机图像分析仪进行定量分析。结果持续压迫各时间组大鼠后肢功能明显减弱,在压迫2 d组大鼠的后肢功能进一步恶化,随着持续压迫时间的推移,大鼠脊髓运动功能有一小幅度的自发性恢复,在持续压迫3周左右时恢复较明显。VEGF的mRNA和蛋白在损伤脊髓组织中广泛表达,压迫1 d组出现大量的免疫阳性细胞,压迫2d组VEGF表达强度达高峰,压迫1周组表达明显下调(P<0.05),压迫3周时降至基础水平。结论在实验大鼠持续性脊髓压迫损伤的发生与发展中,VEGF的表达可能参与了脊髓组织的缺氧耐受及损伤后的修复。     

兔脊髓损伤后钠钾钙镁含量变化及临床意义

目的研究脊髓损伤前后血清及脊髓内钠、钾、钙、镁含量的变化,为临床治疗脊髓损伤提供依据。方法３０只家兔用改良Ａｌｅｎ氏法造成脊髓损伤,６只家兔暴露脊髓不造成损伤。在伤前和伤后６ｈ、２４ｈ、４８ｈ、７２ｈ及６ｄ,用离子选择电极法和原子吸收光谱法测定血清和脊髓组织中离子钠、钾、钙、镁和总钠、钾、钙、镁含量。结果脊髓损伤后,血清中离子钙含量升高,总镁含量下降;脊髓组织中总钙、总钠含量升高,总镁、总钾含量下降。结论脊髓损伤后体内微量元素发生了不同程度的变化。     

Regional Spinal Cord Blood Flow and Energy Metabolism in Rats after Laminectomy and Acute Compression Injury

Many data are available concerning spinal cord blood flow (SCBF) and metabolism on various models and timing after spinal cord injury, however, detailed information on their exact relationship in the same injury model is lacking. This relationship is a crucial factor in the understanding of the pathophysiology of spinal cord trauma. Rats were subjected to lumbar laminectomy or lumbar spinal cord compression trauma. 3 hours later, changes in SCBF were evaluated autoradiographically and changes in ATP, glucose and lactate levels were analyzed using substrate-specific bioluminescence techniques. Measurements were performed at the lesion site (segment L4), adjacent segments (L3 and L5) and at remote thoracic segments (Th8 to Th9). Laminectomy alone did not change SCBF, both in thoracic and lumbar segments. In contrast, ATP levels were significantly reduced and lactate levels were increased at the lesion site and in adjacent lumbar segments at 3 hours after laminectomy, whereas glucose levels were not significantly changed. In animal subjected to additional compression trauma, SCBF was significantly reduced in segments L3, L4 and L5 paralleled by a significant ATP reduction and lactate increase. Glucose levels did not differ significantly from controls 3 hours after compression injury. This metabolic profile was also reflected in the remote thoracic segments. In contrast, SCBF was not reduced in thoracic segments of traumatized animals. The observation that ATP was already significantly reduced and lactate increased in laminectomized segments and in remote thoracic regions after trauma signals that metabolic changes are sensitive indicators to spinal stress. The fact that posttraumatic metabolic profile differs from the pattern of hemodynamic and metabolic changes induced by ischemia, suggests posttraumatic mediators may be involved in the different regulation of the energy producing machinery.     

Tonicity of resuscitative fluids influences outcome after spinal cord injury

OBJECTIVE: This investigation was designed to test the hypothesis that the tonicity of resuscitative fluids administered after spinal cord injury influences the magnitude of secondary injury and, therefore, outcome. METHODS: Rat spinal cords were compressed with 50 g of weight for 5 minutes to produce injury. After spinal cord injury, the animals were randomized into three experimental groups. Group 1 (n = 10) received no fluid resuscitation after spinal cord injury. Group 2 (n = 6) received 5 ml/kg of intravenously administered Ringer's lactate 1 minute after the removal of compression. Group 3 (n = 7) was treated with 5 ml/kg of intravenously administered 7.5% hypertonic saline 1 minute after the removal of compression. Neurological outcome was assessed daily for 10 days using the Basso, Beattie, and Bresnahan locomotor rating scale. Histological evaluations of the spinal cord were obtained on Day 10. RESULTS: The average number of recovery days before the rats were able to spontaneously void their bladders was significantly less (P < 0.05) in the hypertonic saline-treated group. Spontaneous hindlimb movement also occurred sooner in the hypertonic saline-treated animals. The average neurological score was significantly higher (P < 0.05) in the hypertonic saline-treated group during each of the 10 days of recovery. Histological evaluation supported the finding of attenuation of injury in the hypertonic saline-treated animals. CONCLUSION: The results of this investigation with a chronic model of spinal cord injury support the contention that hypertonic saline treatment may provide protection to the spinal cord after mechanical injury.     

Nervous tissue damage markers in cerebrospinal fluid after cervical spine injuries and whiplash trauma

Clinical examination is the only tool available to assess the extent of the nerve tissue damage after a spinal cord injury, and it is well known that the reliability of classification based on clinical examination is not satisfactory, especially in cases with incomplete motor injuries. There is a need to evaluate new methods in order to improve the possibilities of classifying and prognosticating spinal cord injuries. Methods for assessing central nervous system (CNS) damage using markers in cerebrospinal fluid (CSF) have recently been developed. Previous studies have reported glial fibrillary acidic protein (GFAp) and neurofilament protein (NFL) levels in non-traumatic diseases in the central nervous system. The present study is the first report of GFAp and NFL levels in CSF after trauma to the cervical spine. Six cases with cord damage and pronounced neurological deficit showed significantly increased concentrations of both GFAp and NFL in the CSF. Patients with tetrapareses showed higher values than those with incomplete injuries. Three of the 17 whiplash cases had increased levels of NFL, but normal GFAp. Assessment of nervous tissue markers in CSF will probably improve possibilities to classify and prognosticate spinal cord injuries and also to evaluate pharmacological intervention. The increased levels of NFL in three whiplash cases indicate neural damage in a proportion of the cases with neurological deficit. Neurological examinations are presently the only tools for grading and prognostication of spinal cord injuries. Assessment of nervous tissue markers in CSF makes it possible to quantify the degree of nerve cell damage after different types of cervical spine injury ranging from spinal cord lesions to whiplash injuries.     

The efficacy of intrathecal administration of a very low dose potirelin after acute spinal cord injury

Background and object

The objective of this study was to determine the effect of a very low dose protirelin in cerebrospinal fluid (CSF) glucose, magnesium and lactate levels after spinal cord trauma (SCT) in rabbits. We also aimed to evaluate whether this very low dose might induce analeptic effect.

Material and methods

Twenty rabbits were divided equally into two groups: group I (n = 10) was the control group, suffered from SCT but received only saline after SCT. Group II (n = 10) (treatment group), received a very low dose of 0.05 mg/kg thyrotropin releasing hormone (TRH), analogue protirelin intrathecally after SCT. The basal CSF glucose, magnesium and lactate levels were recorded in both groups. CSF lactate, glucose and magnesium contents were recorded at the same time (an hour before and after) SCT. Serum thyroid stimulating hormone (TSH), freetriiodothyronine (FT3) and freethyroxine (FT4) were measured in all rabbits before and after SCT.

Results

Before spinal cord trauma, there were not any significant differences in glucose, lactate and magnesium levels between group I and II whereas, after spinal cord trauma in group II, the significant suppression in elevation of lactate and glucose depletion (p < 0.05) were observed while no significant suppression was observed in magnesium level (p > 0.05) as compared with group I (Table 3). In respect of serum TSH levels, there were not any significant differences between two groups before and after SCT.

Conclusions

This study showed that intrathecal TRH has no analeptic effect on serum TSH, FT3 and FT4 levels but can attenuate the increase of lactate levels following spinal cord trauma. No significant decrease in magnesium level and also suppression of glucose decline in group II, may be related to the neuroprotective effects of TRH.     

Production and clearance of lactate from brain tissue, cerebrospinal fluid, and serum following experimental brain injury

Lactate dynamics in the brain, cerebrospinal fluid (CSF), and serum were studied in 20 chloralose-anesthetized cats following fluid-percussion trauma. Brain lactate and brain tissue pH were measured by hydrogen-1 and phophorus-31 magnetic resonance spectroscopy. The CSF, arterial, and cerebrovenous serum lactate levels as well as serum glucose concentration were quantified. In the six sham-operated control animals, brain, CSF, cerebrovenous, and arterial lactate levels as well as brain pH remained at normal values. In the five animals in the mild-trauma group (1.6 atm), brain and CSF lactate levels were moderately elevated, although the brain pH and serum lactate content remained at control values. Severe trauma (3.1 atm) in nine cats produced an 82% increase in the brain lactate index and a reduction in brain tissue pH (7.02 +/- 0.02 to 6.95 +/- 0.02; mean +/- standard error of the mean), indicating brain tissue acidosis caused by excessive lactate accumulation. Brain lactate levels reached a peak 1 1/2 hours after severe trauma, then steadily decreased to normal levels by 8 hours posttrauma. Maximum increases of CSF and arterial lactate levels (from 1.4 +/- 0.2 to 4.1 +/- 0.4 and from 1.6 +/- 0.2 to 4.1 to 0.6 mmol/liter, respectively) were observed 15 minutes after trauma, and the values decreased during the next 2 hours. The response was biphasic, with a secondary rise observed in both CSF and serum lactate levels during the remaining 4 hours of the experiment. The difference between the arterial and venous lactate levels (A-Vlact) gradually increased and reached a peak 2 hours postinjury (from -0.05 +/- 0.10 to -0.41 +/- 0.09 mmol/liter). The results of this study show that the production of lactate in brain tissue, CSF, and blood increased in proportion to the severity of the injury. The observation that lactate levels in blood and CSF are maximum immediately following impact while brain lactate and A-Vlact are gradually increasing suggests that the brain-tissue production of lactate fails to account for the rapid appearance of lactate in CSF and blood. It is speculated that the initial elevation of CSF lactate values reflects the systemic response of trauma, and the secondary rise of CSF lactate levels following severe trauma is due to slow seepage of lactate produced by brain tissue into the CSF space. These studies are the first to describe the temporal profile of brain lactate production and eventual clearance by CSF and blood in fluid-percussion injury.(ABSTRACT TRUNCATED AT 400 WORDS)     

Prostaglandin E1 reduces compression trauma-induced spinal cord injury in rats mainly by inhibiting neutrophil activation

Prostaglandin E1 (PGE1), a potent vasodilator, was recently reported to inhibit both neutrophil activation and monocytic production of tumor necrosis factor-alpha (TNF-alpha) in vitro. We previously reported that TNF-alpha was critically involved in the development of motor disturbances by increasing the accumulation of neutrophils at the site of injury in rats subjected to compression trauma-induced spinal cord injury. Therefore, it is possible that PGE1 reduces motor disturbances by inhibiting neutrophil activation in rats subjected to spinal cord injury. We examined this possibility in a rat model of spinal cord injury (SCI). Motor disturbances induced by spinal cord compression were evaluated using the inclined plane test, and footprint analysis. Accumulation of neutrophils at the site of trauma was evaluated by measuring tissue myeloperoxydase (MPO) activity. Tissue levels of TNF-alpha were determined using an enzyme-linked immunosorbent assay. Motor disturbances induced by spinal cord compression were significantly attenuated in rats administered PGE1. A histological examination revealed that intramedullary hemorrhages, observed 24 h after trauma, were markedly reduced in animals administered PGE1. Increases in the tissue levels of TNF-alpha and MPO activity in the damaged segment of spinal cord were significantly inhibited in animals that had received PGE1. These observations suggested that PGE1 reduces motor disturbances by inhibiting neutrophil activation directly or indirectly through the inhibition of TNF-alpha production at the site of injury. These effects of PGE1 might at least partly contribute to therapeutic effect on SCI in rats.     

内皮素受体拮抗剂对损伤脊髓早期保护作用

目的评价非选择性内皮素(ET)受体拮抗剂PD145065对损伤脊髓的保护作用,证实ET参与脊髓损伤(SCI)后继发损伤的假设并探讨其作用机制。方法压迫法致伤大鼠脊髓(50g,1min)。损伤前10min鞘内注射PD145065或生理盐水,观察脊髓血流(SCBF)、丙二醛(MDA)、细胞内钙(［Ca2+］i)、伊文思兰(EB)及水含量变化。结果伤区SCBF在伤后5min即有明显下降,为基线的(75.23±9.21)%,2h降为(57.06±7.35)%;伤区邻近血流下降较慢,伤后30min降为(79.82±7.98)%。伤区及邻近区伤后4h?SCBF都未恢复。伤段脊髓组织中MDA、［Ca2+］i、EB和水含量均高于假手术组(P＜0.05)。PD145065明显改善了伤区SCBF,消除了伤区邻近段SCBF的下降。PD145065预处理组脊髓中MDA、［Ca2+］i、EB和水含量均低于生理盐水组(P＜0.05)。结论PD145065对损伤脊髓早期有明显保护作用,ET及其受体可能通过多种途径参与SCI后的继发损伤。临床应用ET受体拮抗剂对SCI可能有治疗作用。     

Role of Na(+)-Ca(2+) exchanger after traumatic or hypoxic/ischemic injury to spinal cord white matter.

BACKGROUND CONTEXT: Spinal cord injury is a devastating condition in which clinical disability results from demyelination of white matter tracts. Changes in glial-axonal signaling, and enhanced Ca(2+) channel activity with excessive accumulation of intracellular Ca(2+), is a common phenomenon after hypoxia/ischemia or mechanical trauma to spinal cord dorsal column white matter tracts leading to irreversible injury. PURPOSE: In the present study we examined the role of Na(+)-Ca(2+) exchanger (NCX) at physiological temperatures after hypoxia/ischemia and compressive injury to spinal cord dorsal column white matter in vitro. STUDY DESIGN: A 30-mm length of dorsal column was isolated from the spinal cord of adult rats, pinned in an in vitro recording chamber (maintained at 37 degrees C) and injured by exposure to a hypoxic atmosphere for 60 minutes or compressed with a modified aneurysm clip (2-gm closing force) for 15 seconds. The functional integrity of the dorsal column was monitored electrophysiologically by quantitatively measuring the compound action potential (CAP) with glass microelectrodes. RESULTS: The mean CAP decreased to 49.5 +/- 5.7% and 49.4 +/- 2.6% of control (p<.05) after hypoxia/ischemia and compressive injury, respectively. KB-R7943, a potent, selective NCX reverse mode inhibitor, significantly promoted greater recovery of CAP amplitude to 82.0 +/- 10.0% and 70.8 +/- 10.7% of control (p<.05) after hypoxic/ischemic or compressive injury to dorsal column white matter, respectively, when applied at 10 microM concentration. Bepridil (Research Biochemical Inc., Natick, MA, USA) (a less selective NCX inhibitor), when applied at 10 microM and 50 microM concentration promoted CAP amplitude recovery only to 46.8 +/- 7.8% and 29.9 +/- 3.3% of control, respectively, after hypoxic/ischemic injury to dorsal column white matter. Western blot analysis identified NCX presence with positive immunolabeling of 160 kD and 120 kD NCX proteins in the spinal cord white matter. CONCLUSION: In conclusion, at physiological temperature NCX activation plays an important role in intracellular calcium overload after hypoxic/ischemic and compressive injury to spinal cord dorsal column white matter in vitro.     

Neuroprotective effect of regional carnitine on spinal cord ischemia--reperfusion injury.

OBJECTIVE: The purpose of this study was to investigate the effect of regional infusion of carnitine on spinal cord ischemia--reperfusion (I--R) in rabbits. METHODS: The 36 rabbits were divided into four equal groups, group I (sham operated, no I--R injury), group II (control, only I--R), group III (I--R+intraaortic lactated Ringer's, LR, during aortic occlusion), group IV (I--R+LR plus 100mg/kg carnitine). Spinal cord ischemia was induced by clamping the aorta both below the left renal artery and above the aortic bifurcation. The spinal cord function of all animals was assessed clinically 24h after aortic declamping. Spinal cord samples were taken to measure the levels of tissue malondialdehyde (MDA) and to evaluate the histopathological changes. RESULTS: We found significant increases in the levels of MDA in groups II and III compared with group I (P<0.01), and elevation of MDA in group IV was insignificant. In group II, all animals (100%) were paraplegic with Tarlov's score of 0 and in group III, eight animals (88%) were paraplegic with Tarlov's score of 0 or 1. None of the animals (0%) from group IV was paraplegic. Histologic examination of spinal cords from group IV animals revealed that the appearance of the spinal cord was relatively preserved, whereas spinal cords from groups II and III had evidence of acute neuronal injury. CONCLUSION: The results suggest that regional infusion of carnitine during aortic clamping reduces spinal cord injury and prevents neurologic damage in rabbit spinal cord I--R model.     

Acute phase effects of ATP-MgCl<Subscript>2</Subscript> on experimental spinal cord injury

The purpose of this study was to study the acute phase effects of adenosine triphosphate (ATP)-MgCl₂ on experimental spinal cord clip compression injury. Spinal cord clip compression injury was performed on 36 albino Wistar rats. The rats were divided into five groups. T4–T8 total laminectomy was performed on all rats. Group 1: sham-operated group. Group 2: clip compression group. In group 3, ATP-MgCl₂ (100 μmol/kg) was given 2 min before the "clip compression injury." In group 4, ATP-MgCl₂ (100 μmol/kg) was given 5 min after the clip compression injury. In group 5, ATP MgC1₂ (100 μmol/kg) was administered 8 h after the injury. The spinal cords were excised for a length of 2 cm and deep frozen at –76°C. Tissue malondialdehyde (MDA) levels were used to determine the effects of ATP-MgCl₂ on spinal cord lipid peroxidation. In the groups in which ATP MgCl₂ was administered after the clip compression injury (groups 4 and 5), the decrease in spinal cord MDA levels was statistically significant when compared with those of the injury group (group 2). Although MDA levels of group 4 were lower than those of group 5, this difference was not statistically significant. Administration of the ATP-MgCl₂ before the clip compression injury (in group 3) did not have a statistically significant effect on lipid peroxidation when compared with the injury group (group 2). In this study, we found that ATP-MgCl₂ has decreased lipid peroxidation in spinal cord injury and protected the spinal cord from secondary injury after the trauma. We concluded that ATP-MgCl₂ may be used in the treatment of spinal cord injuries in conjunction with the other treatment modalities, but further investigations are mandatory. Electronic Publication     

Biochemical alterations in cerebrospinal fluid during thoracoabdominal aortic cross-clamping in dogs

Spinal cord damage during and after thoracoabdominal aortic cross-clamping continues to be a major problem. Somatosensory and motor evoked potentials have been used to monitor spinal cord function but their value for predicting paraplegia has been controversial. The aim of this study was to measure biochemical markers in the cerebrospinal fluid (CSF) and correlate changes with spinal cord ischemia. Since neural tissue utilizes only glucose as substrate for its metabolism and energy supply, we measured changes of metabolites of anaerobe glycolysis. In a canine model in which general anesthesia was used, the thoracoabdominal aorta was cross-clamped proximally and distally for 60 min. Hemodynamic parameters, blood gases, and glucose level were monitored continuously. Blood and CSF sampling were performed at baseline, at 15, 30, and 55 min during cross-clamping, and at 5 and 15 min after aortic declamping. Levels of lactate (1.7 ± 0.1 to 3.2 ± 0.3 mmol/L), pCO2 (43 ± 2 to 35 ± 1.6 mmHg), and neuron-specific enolase (NSE) (5.17 ± 0.5 to 13.0 ± 3.5 mg/L) in CSF showed significant changes (p <0.05) during clamping and reperfusion. Changes in CSF lactate and NSE levels correlate with the duration of spinal cord ischemia. These markers of ischemic metabolism appear suitable to monitor the degree of spinal cord ischemia during thoracoabdominal cross-clamping and may be useful to predict the efficacy of preventive methods.     

Sustained spinal cord compression: part I: time-dependent effect on long-term pathophysiology

BACKGROUND: The objective of this study is to determine whether there is a relationship between the duration of sustained spinal cord compression and the extent of spinal cord injury and the capacity for functional recovery after decompression. METHODS: Sixteen dogs underwent sustained spinal cord compression for thirty or 180 minutes. The cords were compressed with use of a loading device with a hydraulic piston. A pressure transducer was attached to the surface of the piston, which transmitted real-time spinal cord interface pressures to a data-acquisition system. Somatosensory evoked potentials were monitored during a sixty-minute recovery period as well as at twenty-eight days after the injury. Functional motor recovery was judged throughout a twenty-six-day period after the injury with use of a battery of motor tasks. The volume of the lesion and damage to the tissue were assessed with both magnetic resonance imaging and histological analysis. RESULTS: Sustained spinal cord compression was associated with a gradual decline in interface pressure. Despite this, there was continuous decline in the amplitude of the somatosensory evoked potentials, which did not return until the cord was decompressed. Within one hour after the decompression, the dogs in the thirty-minute-compression group had recovery of somatosensory evoked potentials, but no animal had such recovery in the 180-minute group. Recovery of the somatosensory evoked potentials in the thirty-minute group was sustained over the twenty-eight days after the injury. Motor tests demonstrated rapid recovery of hindlimb motor function in the thirty-minute group, but there was considerable impairment in the 180-minute group. Within two weeks after the injury, balance, cadence, stair-climbing, and the ability to walk up an inclined plane were significantly better in the thirty-minute group than in the 180-minute group. The longer duration of compression produced lesions of significantly greater volume, which corresponded to the long-term functional outcome. CONCLUSIONS: The relatively rapid viscoelastic relaxation of the spinal cord during the early phase of sustained cord compression suggests that there are mechanisms of secondary injury that are linked to tissue displacement. Longer periods of displacement allow propagation of the secondary injury process, resulting in a lack of recovery of somatosensory evoked potentials, limited functional recovery, and more extensive tissue damage.     

Shedding of tumor necrosis factor type 1 receptor after experimental spinal cord injury

In a number of stress conditions, the biological effects of tumor necrosis factor-alpha (TNF-alpha), such as the induction of neuronal apoptosis, are presumably attenuated by the soluble fragments of TNF receptors (sTNFRs). Within 1 h after spinal cord injury, increased synthesis and/or secretion of TNF-alpha is detectable at the injury site. However, the shedding of ectodomains of TNFRs in the traumatized spinal cord has not yet been reported. In the present study, adult Sprague-Dawley rats were subjected to acute spinal cord injury (ASCI) by applying a 25-g Walsh-Tator aneurysm clip at the C8-T1 level. Sham-injured animals underwent laminectomy and facetectomy only. A PE10 catheter was placed in the subarachnoid space to collect the samples of cerebrospinal fluid (CSF) from near the injury site. These CSF samples were analyzed by ELISA for the presence of TNF-alpha and soluble TNFR1 and TNFR2 (sTNFR1 and sTNFR2, respectively). The spinal cord tissue was analyzed by immunohistochemistry for the expression of TNF-alpha, TNFR1, and TNFR2, and by the TUNEL technique for the occurrence of neuronal death. The levels of TNFR1 and sTNFR1 in the injured tissue were determined by Western blotting. Immunohistochemistry demonstrated the increased neuronal expression of TNF-alpha and its receptors at 6 h post-ASCI. No changes in the intensity of staining were observed in the sham-injured rats. In addition, at 6 h after the injury, a significant increase in the number of TUNEL-positive neurons was observed. Numerous neurons in traumatized tissue were also immunoreactive for activated caspase-3, suggesting that the TUNEL-positive neurons were undergoing an apoptotic death. At 1 h after ASCI, TNF-alpha levels in the CSF were significantly higher than those found in the sham-injured animals, indicating the release of this cytokine into the interstitial fluid. This was followed by a significant increase, compared to the sham-injured controls, in sTNFR1 levels in the CSF at 3 and 6 h after the insult. Unlike sTNFR1, the levels of sTNFR2 in the CSF were unchanged at any time point post-ASCI. The increased shedding of TNFR1 was confirmed by Western blotting. It is concluded that the shedding of TNFR1 receptor may represent an important post-traumatic physiological response aimed at reducing the proapoptotic effect of TNF-alpha.