Identification of macrophage migration inhibitory factor (MIF) in rat spinal cord and its kinetics on experimental spinal cord injury

BACKGROUND: Among spinal cord injuries, secondary injury is considered to be a "reversible" process and seems to be a key target for the treatment of spinal cord injury. Recently, macrophage migration inhibitory factor (MIF) has been reevaluated as being one of the most important cytokines which act during wound healing, proliferation and differentiation of cells. However, the expression of MIF in the spinal cord has not been investigated yet. PURPOSE: The purpose of this paper is to demonstrate the MIF expression in normal rat spinal cord and to evaluate the kinetics of MIF after spinal cord injury. MATERIALS & METHODS: Female Wistar (280-320 g) rats were studied. Spinal cord injury was made by the clip compression method at the level of C7/Th1 (56 g, For 1 min.). The expression of MIF was examined by immunohistochemistry and northern blot analysis. MIF content in the cerebrospinal fluid (CSF) was measured by enzyme-linked immunosorbent assays (ELISA). Furthermore, to examine the MIF function on neuronal cell, cell proliferation assay (MTS assay) was carried out using PC12, pheochromocytoma cell line, and LN444, glioblastoma cell line, in the presence of anti-MIF monoclonal antibody. RESULTS: MIF stain was positive in normal rat spinal cord white matter. The expression of MIF decreased between 1 hour and 6 hours after injury. It was found to have re-appeared 24 hours after injury. The kinetics of MIF mRNA expression showed reverse-correlation with those of the MIF positive stain. MIF content in CSF was found to be elevated soon after injury. MTS assay suggested that MIF had some proliferative function on neuronal cells. CONCLUSION: MIF exists in the rat white matter. And it's immediately released into the CSF and then re-synthesized 24-hr after injury. MIF shows a cell proliferative function on neuronal cells. These results suggest that MIF plays an important role for secondary spinal cord injury.     

Morphometric study of myelinated fibers in human cervical spinal cord white matter

STUDY DESIGN: Using human autopsy spinal cord specimens, morphologic measurements of myelinated nerve fibers were performed, focusing on the regions that include the main white matter conduction paths. The hemilateral spinal cord morphology was also measured, and its relation with the component myelinated nerve fibers determined. OBJECTIVES: To determine the relation between spinal cord transverse area in the normal lower cervical spine, the site most vulnerable to chronic compressive myelopathy, and myelinated nerve fibers. SUMMARY OF BACKGROUND DATA: Considerable interindividual variation normally is observed in the morphology of the spinal cord transverse area. The influence of this variation on the composition of the white matter myelinated nerve fibers is obscure. METHODS: The C7 segments from seven cadavers were resected, and from magnified photographs of paraffin-embedded specimens, the hemilateral spinal cord area and funicular area were measured. Nerve fiber morphology was measured using Epon-embedded specimens. Three regions that included the main conduction paths were sampled, and magnified photographs obtained. The nerve fiber transverse morphology was measured using the ellipse conversion method, and the myelinated nerve density and fiber area were determined. RESULTS: Marked interindividual variations were found in both the hemilateral spinal cord transverse area and funicular area. A positive correlation was noted between the two, with the spinal cord transverse area large in the cases with a large funicular area. For fiber density and area, histograms were constructed that showed characteristic distribution patterns in each region. By dividing each region into two components (i.e., small- and large-diameter fibers), it was found that the interindividual variation in large-diameter fiber density was small, clarifying that the absolute number of large-diameter fibers compared to fiber density is more strongly dependent on the funicular area. CONCLUSIONS: The absolute number of large-diameter myelinated fibers is smaller in cross-sections of thin as compared to those of thick spinal cord. When elucidating the pathophysiology of compressive myelopathy, it is necessary to study not only the circumstances surrounding the spinal cord, but this kind of factor intrinsic to the spinal cord itself.     

Bronchial hyperresponsiveness after cervical spinal cord injury

Cervical spinal cord injury results in interruption of sympathetic airway innervation, which originates from the upper thoracic spine, whereas parasympathetic nerve supply, arising in the vagal nuclei of the brainstem, remains intact. To assess the effect of such an altered neural environment on airway reactivity, bronchoprovocation testing was performed on eight subjects with nonacute traumatic lesions of the cervical spine, all of whom were lifetime nonsmokers without history of respiratory symptoms prior to their injury. Bronchial challenge was subsequently repeated after pretreatment with the anticholinergic agent, ipratropium bromide, an inhibitor of airway muscarinic receptors. All subjects demonstrated hyperresponsiveness to methacholine (the concentration of methacholine producing a fall in FEV1 of 20 percent from baseline [PC20] = 1.42 +/- 1.61 [SD] mg/ml). Airway hyperreactivity was completely blocked by pretreatment with inhaled ipratropium bromide (mean PC20 > 25 mg/ml [p < 0.0001]). The bronchial hyperresponsiveness observed in this population most likely reflects the loss of sympathetic airway innervation and resultant unopposed cholinergic bronchoconstrictor tone which results from transection of the cervical spine. Blockade of methacholine hyperresponsiveness with ipratropium bromide suggests a muscarinic receptor-mediated phenomenon.     

Delayed postoperative tethering of the cervical spinal cord

Tethering of the spinal cord in the lumbar and sacral regions of children with congenital anomalies is a well-recognized problem; however, tethering in the cervical region has rarely been reported. A search of the literature revealed no reports of symptomatic postoperative cervical spinal cord tethering. The authors present five cases of delayed postoperative cervical spinal cord tethering and discuss the benefit of detethering in these patients. All five patients were young (16 to 42 years of age) at presentation. All had done well after an initial surgical procedure but returned between 1 and 31 years postoperatively with symptoms including severe headache, upper-extremity pain, and progressive neurological deficits. In each case, magnetic resonance imaging indicated dorsal tethering of the cord in the cervical region. Surgical exploration with microscopic sharp detethering of the cervical cord was performed on each patient with favorable results. To avoid retethering, wide Tutoplast duraplasty is recommended.     

Man-in-the-barrel syndrome caused by cervical spinal cord infarction

Ichthyosis bullosa of Siemens is a rare autosomal dominant skin disorder whose clinical findings are quite similar to those of epidermolytic hyperkeratosis. The differences between those two diseases include absence of erythroderma and different distributions in the skin in ichthyosis bullosa of Siemens. Recent studies have confirmed that ichthyosis bullosa of Siemens is caused by the mutation in the keratin 2e (K2e) gene, which is expressed in the upper spinous and granular layers. We have identified a sporadic case of ichthyosis bullosa of Siemens; based on diagnosis by histopathological findings, the K2e gene of the patient was analysed. Direct sequencing of PCR products revealed a single base change in sequences encoding the highly conserved end of the 2B rod domain segment of the K2e gene. This mutation results in substitution of the codon for glutamic acid by a codon for lysine in position 493 in K2e (E493K). Mutations of the K2e gene involving five different residue positions (Q187P, T485P, L490P, E493D, E493K and E494K) are known to cause ichthyosis bullosa of Siemens. Of these sites, E493, which is conserved in type I and type II keratin genes, is the most frequently altered amino acid in the K2e gene. These data together suggest that this codon constitutes a hot spot for mutations in the K2e gene.     

Magnetic resonance imaging in cervical spinal cord compression

In patients with cervical spondylotic myelopathy MRI sometimes shows increased signal intensity zones on the T2-weighted images. It has been suggested that these findings carry prognostic significance. We studied 56 subjects with cervical spinal cord compression. Twelve patients showed an increased signal intensity (21.4%) and a prevalence of narrowing of the AP-diameter (62% vs 24%). Furthermore, in this group, there was evidence of a longer mean duration of the symptoms and, in most of the patients, of more serious clinical conditions. The importance of these predisposing factors remains, however, to be clarified since they are also present in some patients without the increased signal intensity.     

Angiographic changes following acute spinal cord compression: an experimental study in monkeys

Acute paraplegia was produced in monkeys by abruptly inflating a balloon catheter within the epidural space. The arteriographic and epidural venous changes following such trauma were serially evaluated. Spinal-cord arteriograms following cord injury remained normal during an acute (four-hour) follow-up. Serial epidural venograms demonstrated obstruction of epidural veins within four hours at the site of contusion in less than half of the animals studied. Neither spinal arteries nor epidural showed consistent diagnostic changes following trauma due to acute epidural compression.     

Motor recovery following spinal cord injury associated with cervical spondylosis: a collaborative study

A prospective multicenter study was conducted within the National Model Spinal Cord Injury System program to examine neurological deficits and recovery patterns following spinal cord injury (SCI) in individuals with cervical spondylosis and without a spinal fracture. Nineteen patients were evaluated. Sixty-eight percent presented initially with motor incomplete lesions. Of those who presented with motor incomplete injuries at their initial examination, 69 percent had less deficit in the lower than in the upper extremities, indicative of a central cord syndrome. At follow-up, 12 subjects were unable to ambulate, four required assistance and three were able to ambulate independently. On the average, subjects doubled their initial Asia Motor Score (AMS) scores by one year following injury. Residual upper extremity weakness, however, limited the ability to ambulate. Recovery of motor strength in this group is comparable to that of individuals with incomplete tetraplegia in general but the proportion who regain ambulatory function is less.     

Lymphoma of the spinal extradural space

Ninety-four patients with lymphoma involving the extradural space with spinal cord compression proven at the time of laminectomy were reviewed. There were about three times as many patients with non-Hodgkin's lymphoma than with Hodgkin's disease. The majority of those with Hodgkin's disease had a proven histologic diagnosis before the onset of the spinal cord compression syndrome, whereas only 15% of those with non-Hodgkin's lymphoma had previously been so diagnosed. Plain roentgenograms of the spine were suggestive of tumor involvement in less than one-third of the patients, whereas myelograms were invariably abnormal. As noted by others, the outlook for functional recovery and extended life expectancy is relatively good for patients with this type of cancer, in contrast to reports in the literature regarding prognosis for patients who have metastatic carcinoma with extradural spinal cord compression.     

Predicting neurologic recovery in traumatic cervical spinal cord injury

OBJECTIVE: Traumatic spinal cord injury (SCI) affects 8,000 to 10,000 individuals per year in the United States. One of the most difficult tasks confronting the clinician is the discussion of neurologic recovery and prognosis with the patient and/or family. Our objective is to provide a guide for practitioners to accurately predict neurologic outcome in acute traumatic cervical SCI (tetraplegia). DATA SOURCE: Published reports obtained through MEDLINE search, texts, and studies presented at national conferences. STUDY SELECTION: Peer reviewed studies, in English language, that discussed prognosis after traumatic SCI. CONCLUSION: A comprehensive physical examination of the acute SCI patient is essential in determining the initial level and classification of the injury and is the most accurate method to predict neurologic recovery. Other diagnostic tests, including somatosensory evoked potentials, magnetic resonance imaging, and transcranial magnetic stimulation, may be helpful in further determining outcome when used in association with the clinical examination. The understanding of neurologic recovery should help predict ultimate functional capability and potential needs.     

The development of intramedullary cavitation following spinal cord injury: an experimental pathological study

It is concluded from this investigation that localised intramedullary cavitation will develop following non-disruptive spinal cord trauma if the magnitude of original trauma and resulting vascular damage is sufficient. Although an adhesive arachnoiditis also occurs with similar amounts of trauma, the initial vascular damage and subsequent reparative changes within the spinal cord appear to adequately explain the cavitation observed.     

The effect of prolonged spinal cord compression on the extent of morphological changes in experimental spinal cord injury in rabbits

The analysis of early spinal cord decompression influence on the extent of morphological and microvascular changes after traumatic cord injury was the subject of this study, carried out on Polish-breed rabbits divided into two groups. Microvascular changes were evaluated in the first group of 20 animals and morphological changes in the second group of 36 rabbits. The injury causing paraplegia was performed at D9-D10 level by Allen method modified. Every group was subdivided into 4 subgroups depending on the duration of cord compression 2, 4, 6 and 12 hours. Fragments of cord were taken for examination 12 hours after decompression, from sites 0.5, 1.0 and 1.5 cm distant from the injury level. Histopathological analysis was performed by light and electron microscopy and for the analysis of microcirculation with microangiography the Górkiewicz method was used. Great changes were found in nerve fibres, vascular endothelium and microcirculation. The most pronounced lesions were found in the subgroup with 6-hour compression, in the form of haemorrhage, central necrosis and oedema within and around axona as well as destruction of myelin sheaths. Early decompression (within 6 hours) can reduce the extent of morphological and vascular changes.     

Epidural perfusion cooling protection against protracted spinal cord ischemia in rabbits

In in vivo allogeneic bone marrow transplantation studies with the Brown Norway (BN) rat as recipient and the WAG/Rij rat as allogeneic donor a significant graft-versus-leukemia (GVL) effect is observed. Studies were performed to investigate whether lymphokine-activated killer (LAK) cells play a role in this GVL effect. Splenocytes from WAG/Rij and BN rats were activated in vitro by recombinant human interleukin-2 (rhIL-2) for 5-6 days. The cytolytic activity of these LAK cells was tested on four rat solid tumor cell lines, i.e. an ureter carcinoma, a rhabdomyosarcoma, and two lung tumors, and on leukemic cells derived from the BN rat acute myelocytic leukemia (BNML) and the WAG/Rij acute lymphocytic leukemia (L4415). The panel of target cells also included the murine cell lines P815 and YAC. Both WAG/Rij and BN LAK cells were not capable of lysing the leukemic cells in contrast to significant cytolytic activity on the rat solid tumor cell lines and P815 and YAC. BNML cells showed to be resistant to lysis by human NK cells. Phenotypical analysis of the rat LAK population revealed a decrease in the CD4/CD8 ratio compared to the unstimulated splenocyte population. Rat LAK cells displayed no antibody-dependent cellular cytotoxicity (ADCC) on the leukemic cells, whereas IL-2-stimulated human peripheral blood cells showed moderate ADCC activity on the leukemic cells. To investigate whether cytokines play a role in lysis of leukemic target cells, graded numbers of LAK cells and leukemic cells were co-cultivated for seven days in an agar-based colony culture system. This resulted in moderate suppression of leukemic colony formation. From the current in vitro studies it appears that the graft-versus-leukemia observed in in vivo allogeneic bone marrow transplantation studies is probably not due to a direct leukemic cell kill by LAK cells.     

Magnetic resonance imaging of experimental subacute spinal cord compression

STUDY DESIGN: Subacute compression of the spinal cord was applied to rats. The animals were chronologically observed using magnetic resonance imaging for more than 8 weeks after surgery and were killed for histopathologic examination. OBJECTIVES: To investigate the correlation of changes in signal intensity on magnetic resonance images with those observed in histopathologic study and with the degree of spinal cord compression and paralysis. SUMMARY OF BACKGROUND DATA: No consensus has been reached concerning the correlation of magnetic resonance images to clinical symptoms of compressive myelopathy. Few reports are available in which magnetic resonance imaging findings are compared with histopathologic features in chronic or subacute experiments. METHODS: In rats under general anesthesia, the T11 lamina was thinned and a slow increase in volume was applied. Hind limb paralysis appeared 1 week after the procedure and spontaneously subsided thereafter. The degree of spinal compression and signal intensity was observed chronologically using magnetic resonance imaging. The signal intensity on the final MR images was rated on a four-point scale and compared with histopathologic findings. RESULTS: As spinal compression increased, the incidence of high signal intensity on long spin-echo images became higher. Low signal intensities on short spin-echo images were visible in animals in which compression and paralysis were the most severe. In these animals, cavitation and a dilated central canal were visible. High signal intensities on long spin-echo images reflected various pathologic changes. CONCLUSIONS: Changes in signal intensity on MR images are visible after the induction of myelopathy by high-pressure compression. These signal intensities may be useful in predicting the outcome of compressive myelopathy.     

Intraoperative ultrasonographic evaluation of the spinal cord in cervical myelopathy

This article describes the construction of a 15-item short-form of the Scale of Egalitarian Sex Role Attitudes (SESRA-S) based on factor analysis and examines the reliability and the validity of the short-form using data from a sample of 109 men and 93 women. SESRA-S is a self-report measure of the level of egalitarian attitudes toward the roles of men and women. Its reliability coefficient was .91, the test-retest coefficient with a four-week interval .89, and the correlation coefficient with the full form .94. These support the reliability of the short-form. Evidence of the construct validity was derived from the confirmation of five hypotheses regarding gender, educational attainment, women's employment status, age, and surname change after marriage. The findings of the present study provide evidence for the utility of the short-form as a satisfactory and time-efficient substitute for the SESRA full form.     

A study of adenosine treatment in experimental acute spinal cord injury. Effect on arachidonic acid metabolites

STUDY DESIGN: A prospective, randomized, blinded experimental trauma study. STUDY OBJECTIVE: The effect of adenosine on arachidonic acid metabolites and lipid peroxidation was investigated in induced spinal cord injury. SUMMARY OF BACKGROUND DATA: Effects of adenosine in ischemia-reperfusion models have been studied, but no studies of adenosine's effect on direct trauma to the spinal cord have been reported. METHODS: Thirty-seven adult Wistar albino rats were randomly divided into four groups and underwent laminectomy. Group 1 underwent a sham operation. Group 2 received an intravenous adenosine infusion of 100 micrograms/kg per minute for 30 minutes. In Group 3, a standard spinal cord trauma of 50 g.cm strength was established at the lower thoracic level with a "weight-drop" technique, and Group 4 received an infusion of adenosine (100 micrograms/kg per minute) for 30 minutes after the trauma. RESULTS: Tissue prostaglandin E2 activity was significantly higher in adenosine-treated trauma groups when compared with that in other groups (P < 0.0001). The difference in tissue leukotriene C4 activity between control and trauma groups was significant (P < 0.05). Adenosine infusion after trauma limited the increases in lipid peroxidation, with the difference approaching significance at P = 0.06. The structure of myelin was well preserved in the adenosine-treated trauma group. However, the changes were irreversible in severely damaged areas. CONCLUSION: After acute spinal cord trauma, intravenous adenosine infusion of 100 micrograms/kg per minute could attenuate progression to secondary injury, but adenosine alone was not effective yet.     

Gastric myoelectrical activity in patients with cervical spinal cord injury

OBJECTIVE: Dyspeptic symptoms are common in patients with cervical spinal cord injury (SCI). The supraspinal control of sympathetic innervation to the stomach is interrupted in these patients. Gastric emptying has been reported to be delayed in some patients with cervical SCI. Gastric myoelectrical activity is known to regulate gastric motility and is correlated with gastric emptying. The change in gastric myoelectrical activity after cervical SCI is unknown; our aim was to investigate it. METHODS: The study was performed in 12 cervical SCI patients and 14 healthy controls. Gastric myoelectrical activity was recorded using surface electrogastrography for 30 min in the fasting state and 1 h after a standard test meal. Spectral analysis was performed to compute the following parameters from the electrogastrogram; investigated were the percentage of 2-4 cycles/min (cpm) slow waves, the instability coefficient (IC) of the dominant frequency, the postprandial increment of dominant frequency (deltaF), and its power (deltaP). RESULTS: In both fasting and fed states, regular and stable gastric slow waves were observed in both the control group and patients with cervical SCI. The percentage of normal 2-4 cpm slow waves (preprandial, 80.7+/-3.6% vs 91.5+/-3.7%, p > 0.05; postprandial, 82.0+/-4.4% vs 87.2+/-4.2%, p > 0.05) and IC (preprandial, 0.19+/-0.04% vs 0.28+/-0.05%; postprandial, 0.24+/-0.04% vs 0.27+/-0.02%, p > 0.05) were not significantly different between the two groups. The dominant frequency and its power were also similar between the two groups, no matter whether in the fast (frequency, 2.92+/-0.3 vs 2.93+/-0.06 cpm; power, 30.05+/-1.29 vs 29.08+/-1.23 dB, p > 0.05) or fed (frequency, 3.17+/-0.07 vs 3.02+/-0.06 cpm; power, 32.55+/-0.90 vs 32.07+/-1.18 dB,p > 0.05) state. The postprandial response measured by deltaF (0.25+/-0.09 vs 0.09+/-0.07 cpm, p > 0.05) and deltaP (2.52+/-1.10 vs 2.24+/-1.20 dB, p > 0.05) were also similar between the two groups. CONCLUSION: Gastric myoelectrical activity was not altered after cervical SCI.