Central nervous system trauma : journal of the American Paralysis Association最新文献

Spinal cord injury has been studied using a cat compression model. Very early changes in lipid metabolism were found that compromise the integrity of the plasma membrane and decrease the activities of ATPases. Up to 18% of the ethanolamine plasmalogens are lost, with very marked elevations of the free fatty acids, arachidonic acid, diacylglycerols, prostaglandins, thromboxanes, and leukotrienes. These changes result in edema, inflammation, necrosis of oligodendroglia, demyelination, and paralysis.

The calcium-channel blocking agent, nimodipine, was administered to cats for 5 days after acute experimental SCI. Six weeks after injury, no significant differences in neurologic recovery or white matter tissue preservation at the injury site were found between treated and control animals.

A review of current techniques and results of monitoring spinal cord function by the intraoperative testing of somatosensory evoked potentials is given. The criteria for an ideal monitoring method are defined: (1) potential alterations occur before the lesion is irreversible, (2) monitoring itself does not harm the patient, (3) there are no false-positive or false-negative results, (4) warning criteria are defined by objective and quantifiable parameters. In recording and stimulation, two different approaches are applied: cortical or spinal recording and peripheral or spinal stimulation. Spinal stimulation techniques are considered more invasive, but an averaged potential is obtained quicker and more reliably by spinal methods. Failure rates in establishing useful monitoring procedures vary between 2.85 and 5%. The N2O-analgesic-relaxant-type of anesthesia is recommended. A precise definition of criteria indicating spinal cord damage has been difficult because of the natural variability of intraoperative evoked potentials. Wide ranges of physiologic, anesthesiologic, and technical and surgical factors have been found to influence intraoperative potential monitoring adversely. The so-called warning criteria drawn from evoked potential changes have so far been set arbitrarily: amplitude reductions of 30-50% for several recordings or at least 15 minutes have mostly been used. It has become clear, however, that warning criteria should be different for healthy or impaired spinal cord function and for cortical and spinal recordings. The value of a lesion-specific spinal cord potential for monitoring remains to be clarified. SEPs are sensitive for demonstrating ischemic changes to the spinal cord, but the limited experience with these lesions does not allow firm conclusions regarding the reversibility of clinical and evoked potential changes in spinal cord ischemia in man. The limited experience with multilevel recording, i.e., simultaneously recording at spinal and cortical level, indicates that epidural recordings are less variable and less failure-prone than cortical recording. Simultaneous multilevel recording also gives more information and allows easier recognition of false-positive or false-negative results. Poor preoperative SEP nearly always preclude useful monitoring. The results obtained so far point out areas where further development is necessary in order to increase the efficacy of this method. Major unsolved problems are (1) definition of warning criteria, (2) incidence of false-positive and false-negative findings, and (3) improvement of data acquisition.(ABSTRACT TRUNCATED AT 400 WORDS)

The development of permanent paraplegia in spinal injured cats is accompanied by a large progressive decline in total ascorbic acid (AA) and a transient increase in oxidized (AAox) ascorbate. Since AA is involved in a variety of processes required for normal central nervous system (CNS) performance we suggested that such large ascorbate loss may contribute to derangements in spinal cord function following injury. We now demonstrate that methylprednisolone (15 mg/kg) and naloxone (10 mg/kg), two treatments that preserve neurologic function in this model, rapidly block deteriorating ascorbate status. Naloxone at 1 mg/kg, a treatment providing no therapeutic benefit, has no protective effect on ascorbate. The results strongly support the hypothesis that loss of ascorbate homeostasis reflects irreversible loss of neurologic function following spinal cord injury.

Major sources of data on incidence and prevalence of spinal cord injury (SCI) in the United States were reviewed, including many federal government agencies, state level rehabilitation and health departments, regional SCI systems, private voluntary organizations, available literature, and several unpublished studies. With the exception of the Veterans Administration, many of the federal databases did not prove helpful. For example, the estimates of the annual surveys conducted by the National Center for Health Statistics (NCHS) of traumatic SCI are likely to be inflated due to multiple hospital admissions of the same patient and deflated due to misclassification of SCI. The tendency for inflation and deflation, however, may balance each other, resulting in a rough estimate of annual traumatic SCI incidence of about 11,000 for 1984. Data from the Florida and Virginia Central Registries of SCI suggest a decrease in traumatic SCI incidence in recent years. Based on data abstracted from a regional study, the California Disability Survey, we estimate the prevalence of traumatic SCI to be about 238,000 in the United States for 1984.

The course of axonal and vascular change following trauma was investigated in an animal model of fluid-percussion brain injury. To assess axonal change, the anterograde transport of horseradish peroxidase in selected cerebral and cerebellar efferents was studied in cats that had sustained minor to moderate injuries and had survived the traumatic episode for periods ranging from several hours to several months. To assess vascular change, cats were equipped with cranial windows, which allowed for both the direct functional study of the pial vasculature following injury and the postmortem harvesting of the studied vessels for morphologic analyses. Following fluid-percussion brain injury, a subtle focal perturbation of the axon occurred, and over a 12 to 24 hour period, this perturbation became progressively severe, with the result that the axon swelled, separated from its distal segment, and thereby formed an enlarged reactive swelling. With continued survival, some swellings persisted intact, others degenerated, and others demonstrated a dramatic regenerative response. This regenerative response, characterized by regenerative sprouting and growth conelike outgrowths, persisted through all survival periods considered. Immediately following the induction of the fluid-percussion injury, the pial arterioles dilated, manifested morphologic change, and displayed functional abnormalities. These vascular abnormalities appeared mediated by an accelerated metabolism of arachidonate via cyclooxygenase, which results in the generation of oxygen radicals. Radicals, such as the superoxide anion, continue to be produced within the first hour following injury and thus, similar to the observed axonal responses, continue to contribute to the brain's response to trauma. Although these axonal and vascular changes do not appear to be causally related, they both appear as a continuum of the initial insult and may become interlinked should a secondary insult ensue.

The ability of the cyclooxygenase inhibitor ibuprofen to affect early neurologic recovery following a moderately severe concussive head injury was studied in male CF-1 mice. Each mouse received a 900 g-cm (50 g weight dropped 18 cm) head injury, followed within 5 minutes with a single IV dose of ibuprofen (sodium salt; 1, 3, 10, or 30 mg/kg). At 1 hour postinjury, their neurologic status was assessed using a grip test. Drug administration and neurologic evaluation were carried out blindly. A dose-related improvement in recovery was observed, with a 10 mg/kg IV dose causing a 122% increase in the mean grip test score compared to 0.9% saline treatment (p less than 0.01 by one-way ANOVA). In addition, there was a significant decrease in the number of mice in the 10 mg/kg ibuprofen group that fell off the grip test string in 0-5 seconds (i.e., that were severely impaired). In comparison, neither the selective thromboxane A2 synthetase inhibitor furegrelate sodium, the stable epoprostenol (PGI2) analog ciprostene calcium, nor the selective 5-lipoxygenase inhibitor piriprost potassium caused any therapeutic effect. The highest dose of the TXA2 synthetase inhibitor (30 mg/kg IV) actually had a statistically significant detrimental action that appeared to be due to an increase in posttraumatic cerebral hemorrhage. The possible mechanisms of the beneficial effect of ibuprofen in acute head injury are discussed in relation to an attenuation of the synthesis of vasoactive arachidonic acid metabolites (e.g., prostaglandin F2 alpha, thromboxane A2) and oxygen-free radical-induced lipid peroxidation.

To study neuron-glial interactions, our laboratory has developed an in vitro model system that, when used with cell type-specific antisera, allows visualization of contacts between cerebellar granule neurons and astroglia. When cells were dissociated from early postnatal mouse cerebellum and plated in microcultures, the neurons aligned along glial filament protein (GFP)-containing astroglial processes. The behavior of the neurons depended on the shape of the particular astroglial cell that they contacted. Neuronal migration commonly occurred along highly elongated astroglial processes of Bergmann-like glia but was inhibited when neurons nestled among the arms of stellate astroglia. To analyze the influence of neurons on the astroglial shapes associated with neuronal migration, cerebellar granule neurons and astroglia were purified and recombined. In the absence of neurons, cerebellar astroglia assumed a flattened shape and proliferated rapidly. In the absence of astroglia, neurite outgrowth was severely impaired. When neurons were recombined with purified astroglia, astroglial proliferation slowed markedly, the shape of the astroglia transformed into complex forms, and neuron-glial interactions were seen. In tissue sections, immature forms of glia were found in the developing cerebellar axon tracts, but no obvious relationship could be discerned between the growing axonal tips and the glia. At P7, a period when the growth of cerebellar axons slows markedly, a transient natural gliosis was seen in the putative white matter. These studies underscore the interdependence of neurons and astroglia during periods of neuron differentiation and neurite outgrowth. In addition, they raise the possibility that the disruption of normal neuronal-astroglial contacts suffered during CNS injury could lead to defects in astroglial form and surface properties that, in turn, might impair axon regrowth.