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

Changes in norepinephrine and histamine levels in the spinal cord of monkeys at 1/2, 2, and 4 hours after 200 g cm of contusion injury, 50 g of compression injury, and 2 hours of decompression following 4 hours of compression were studied in the traumatized and an adjacent nontraumatized segment. Norepinephrine levels were elevated in the traumatized segment at 1/2, 2, and 4 hours after contusion injury and in the adjacent nontraumatized segment at 1/2 hour. Compression of 1/2 and 2 hours caused elevation of norepinephrine in both the traumatized and nontraumatized segments. On decompressing the values of norepinephrine reverted to near normal levels. Histamine content increased in the traumatized segment at 2 and 4 hours after contusion injury and in the adjacent nontraumatized segment at 2 hours. Compression injury did not change histamine levels, but decompression caused an increase. The possible influence of simultaneous changes in norepinephrine and histamine levels on the vessels following injury is discussed.

Physical and biochemical changes in the spinal cord of monkeys at 1/2, 2, and 4 hours following 200 g cm contusion injury and 50 g of compression injury and 2 hours of decompression following 4 hours of compression were studied. The pathophysiologic changes were milder in compression compared to contusion injury. Following contusion injury, at 1/2 and 2 hours there was significant increase in % water content, lipid peroxidation, and alpha-L-fucosidase. alpha-D-Mannosidase was significantly increased at all time periods, and beta-D-hexosaminidase was increased at 1/2 and 4 hours. At 4 hours following injury, serotonin (5 HT) and 5-hydroxyindole-3-acetic acid (5-HIAA) showed a significant increase. From 10 minutes to 2 hours there was increased platelet aggregation. In compression injury, a significant increase in water content and 5 HT was observed only at 1/2 hour. Lipid peroxidation had increased at all time periods, whereas B-D-hexosaminidase, beta-D-galactosidase, and 5-HIAA were increased at 2 hours. alpha-D-Mannosidase had increased at 1/2 and 2 hours, and alpha-L-fucosidase had increased at 4 hours. After 2 hours decompression following 4 hours compression, water content, beta-D-galactosidase, and alpha-D-Mannosidase were significantly increased. An attempt was made to correlate the findings and to understand the sequential pathophysiologic changes in the first 4 hours following spinal cord trauma, providing a baseline for evaluation of the efficacy of any therapeutic maneuvers.

Electronic averaging makes it possible to analyze somatosensory evoked potentials (SEP) recorded noninvasively from the body surface in man. With noncephalic reference recording, the SEP discloses a series of components that are volume-conducted from distinct open-field generators with a geometry adequate to produce external potential gradients over the head. Farfields are brief positive dips with widespread distribution that present stationary onset and peak latencies all over. They reflect the propagated afferent volley in axons bundles, thus in brachial plexus (P9), dorsal column (P11), and medial lemniscus (P14). Somehow unexpectedly, SEP traces also disclose a widespread prolonged farfield N18 of negative polarity that reflects neural generators in the brainstem below thalamus. Nearfields can be positive or negative, and they reflect neural generators located less than about 50 mm from the electrode. They are influenced to a greater extent by the position of the recording electrodes. For example, neck electrodes can follow the upward propagation of the dorsal column volley (N11), whereas scalp electrodes can map out the distinct contralateral parietal (N20, P27) or frontal (P22, N30) cortical generators. Electrodes around the neck also disclose the posterior N13 and anterior P13 responses that reflect the two sides of the same dorsal horn generator with a horizontal axis. Bit-mapped topographic color imaging of potential fields provides detailed data on time and spatial features of the different SEP neural generators. SEP neuromonitoring can use these results to titrate input to spinal cord (nerve potentials or P9 farfield), spinal generators (N11 nearfield or N13-P13 nearfield in posterior-to-anterior neck montages), brainstem generators (P14 farfield and N18 response), or cortical generators (parietal N20-P27 or frontal P22-N30). The central somatosensory conduction time can be titrated from the spinal entry and cortical arrival times measured in neck and scalp recordings.

A variety of physiologic, neurochemical, and morphologic sequelae have been either shown or postulated to result from spinal cord injury, yet the actual pathophysiologic substrate that leads to the loss of neurologic function remains uncertain. Several treatment modalities have been investigated in spinal cord injury, but little consensus exists regarding their efficacy. Steroids in particular have been studied extensively with little agreement about their effects and possible mechanism of action. Recently naloxone has been found to improve neurologic function following spinal cord injury, and its effectiveness has not been challenged to date. In the past most attempts at therapy in cases of brain injury were directed at control of edema, and, consequently, clinically beneficial effects were usually ascribed to control of the edematous process. This was particularly so in the case of steroids. Currently, emphasis has shifted to the study of various neurochemical systems (eicosanoids, serotonin, catecholamines) that, independently from edema may underlie functional disturbances resulting from trauma. Much of the pertinent information derives from the use of drugs in freezing lesion models of brain injury.

The interactions between lipid peroxidation and calcium in mediating damage to central nervous system membranes have been examined in several in vitro systems. Using isolated rat brain synaptosomes, brain mitochondria, or cultured fetal mouse spinal cord neurons, Ca2+ was found to markedly enhance lipid peroxidation-induced disruption of membrane function. Gamma-aminobutyric acid (GABA) uptake by synaptosomes was inhibited 25% by either lipid peroxidation (induced with xanthine and xanthine oxidase) or Ca2+ alone, whereas inhibition was 46% with their combination. Ca2+ enhancement of lipid peroxidation-induced damage to synaptosomes was intensified by the Ca2+ ionophore, A23187, and was partially blocked by the Ca2+ channel blocker, verapamil. Similarly, inhibition of state 3 respiration in isolated rat brain mitochondria was observed with Ca2+ and a free radical generating system (xanthine and xanthine oxidase) under conditions where either insult alone failed to cause detectable damage. Na+,K+-ATPase activity of cultured fetal mouse spinal cord neurons was inhibited 32% when cells were incubated for 30 minutes in the presence of both A23187 and a free radical generating system. However, Na+,K+-ATPase was not affected during a 30 minute incubation with either A23187 or radical generating system alone. In further studies, peroxidation of rat brain synaptosomes by ferrous iron (Fe2+) and H2O2 was coupled with a rapid and large (2-7-fold) uptake of Ca2+ by synaptosomes. Fe2+ also enhanced Ca2+ uptake by spinal cord neurons in culture, an effect that was coincident with peroxidation of neuronal membranes and the release of arachidonic acid from cells. Iron-induced Ca2+ uptake was blocked by high concentrations of either desferrioxamine or methylprednisolone, whereas Ca2+ channel blockers did not affect Ca2+ uptake induced by Fe2+. Finally, peroxidation of membrane lipids by Fe2+ was stimulated by Ca2+. Concentrations of Ca2+ as low as 10(-9) M increased peroxidation reactions within brain synaptosomal membranes. The results of these studies indicate that lipid peroxidation and Ca2+ can synergistically act to damage biologic membranes. The findings suggest that Ca2+ and lipid peroxidation cannot be considered as separate entities in the pathophysiology of CNS trauma. A hypothesis proposing an inseparable interplay between lipid peroxidation and Ca2+ in the pathogenesis of traumatic and ischemic cell injury is presented.

Head trauma is a significant source of morbidity in the United States each year. Approximately 700 patients were admitted to our surgical intensive care unit with some degree of head trauma in a 24-month period. Glasgow Coma Score (GCS) was 8 or less in 90% of this group, and 3 or 4 in 43%. Sensory evoked responses were recorded in over 500 patients. This study is reported to demonstrate that optimum care of the injured brain depends on titration of care aimed at maintaining normal neuronal function. In our series, 25% of the patients with GCS of 3 or 4 returned home or to a rehabilitation unit, a significant decrease in morbidity over other reported series. Chemical paralysis and barbiturate coma were a factor in the decision to monitor in 50-60% of the series. In these patients, the auditory brainstem evoked response (ABR), a monitor of brainstem neuroelectrical function, and the somatosensory evoked response, a monitor of brainstem and cortical function, were used to follow the effectiveness of medical and surgical management in these patients, since neurologic examination was of limited value. Case reports are presented to demonstrate that even at high barbiturate levels, access to the integrity of the central nervous system is still possible. Relations among GCS, computerized tomography (CT), intracranial pressure (ICP), ABR, pupillary response, and outcome were studied for a subgroup of 114 patients. All of these clinical parameters, except CT findings, were significantly correlated with outcome using Chi-square analysis. When the data were further analyzed with linear regression analysis, however, the only parameters that significantly correlated with outcome were pupil reactivity and ABR. The principal conclusion of this report is that the main application of serial monitoring of the sensory central pathway in the head-injured patient is not in the prediction of outcome but in the titration of care of the patient for the preservation of neuronal function.

Recent studies of the chronic morphology and physiology of experimental spinal cord injury (SCI) in the cat are reviewed and their conclusions outlined. In particular, variations in chronic dysmyelination of the lesion have been found to be largely independent of injury intensity, suggesting a secondary pathologic origin. New morphometric studies of the subacute development of contusion lesions are described. Using electron microscopy and light microscopic line-sampling of myelinated axons, it was found that demyelination of axons that survived the initial injury occurred largely between 2 and 7 days after contusion and did not accompany the much more rapid dissolution of myelin from those axons that degenerated within the first 2 days. The number of apparently intact axons at the center of the lesion declined by a factor of 2 or more in the same interval of 2-7 days. This secondary pathology was coincident with dense invasion of the lesion by macrophages and their phagocytosis of the membraneous debris remaining from the initial hemorrhagic necrosis. It is concluded that posttraumatic inflammation in the spinal cord should be investigated in more detail as a possible contributor to chronic deficits. In addition, these data emphasize the importance of defining the nature, time of occurrence, and proportional significance of secondary damage in order to evaluate those studies and hypotheses that attempt to differentiate acute secondary pathophysiology from primary degenerative processes.