A novel sensory evoked potential for selective monitoring of the ventral spinal cord: from bench to bedside.
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Adult↗
Biomedical subjects
C H Tator
Publications and source records attributed to C H Tator.
Characterization of axonal ultrastructural pathology following experimental spinal cord compression injury.
The present study characterizes axonal pathology associated with traumatic compression injuries of the spinal cord and quantitatively assesses subtypes of axonal pathology in the acute, post-injury period. Eighteen adult female Wistar rats underwent spinal cord compression injury with a 53 g modified aneurysm clip at the C8-T1 segment. Six additional rats served as sham controls. Six experimental animals were sacrificed at each of the three post-injury time points: 15 min, 2 h and 24 h. From all animals, the C8-T1 spinal cord was dissected and processed for both light and electron microscopy. Axonal pathology included periaxonal swelling, organelle accumulation, vesicular myelin, myelin invagination, myelin rupture, and giant axons. Early myelin rupture and the ultrastructural features of giant axons are described here for the first time in the context of spinal cord compression injury. The quantitative analysis characterizes the prevalence of types of axonal pathology over the acute post-injury period and provides evidence for the secondary injury hypothesis regarding the evolution of axonal pathophysiology following trauma.
Animals↗
The relationships among the severity of spinal cord injury, residual neurological function, axon counts, and counts of retrogradely labeled neurons after experimental spinal cord injury.
Substantial residual neurological function may persist after spinal cord injury (SCI) with survival of as few as 5-10% of the original number of axons. A detailed understanding of the relationships among the severity of injury, the number and origin of surviving axons at the injury site, and the extent of neurological recovery after SCI is of importance in understanding the pathophysiology of SCI and in designing treatment strategies. In the present study, these relationships were examined in rats with graded severity of clip compression injury of the cord at T1. The rats were randomly assigned to one of the following injury groups (n = 5 each): normal (laminectomy only), 2-, 18-, 30-, 50-, and 98-g clip injuries. Neurological function was assessed by the inclined plane method and by the modified Tarlov technique. A morphometric assessment of axons at the injury site was performed by a computer-assisted line sampling technique. The origin of descending axons at the injury site was determined by retrograde labeling with horseradish peroxidase. The inclined plane scores varied as a negative linear function of the closing force of the clip used to inflict SCI (r = -0.93; P < 0.0001). The mean axon count was 367,000 +/- 59,000 in normal rats and decreased as a negative exponential function of injury force (r = -0.92; P < 0.0001). As well, SCI caused preferential destruction of large axons as reflected by the change in mean axon diameter from 1.74 +/- 0.06 microns in normal cords to 1.46 +/- 0.04 microns in injured cords (pooled mean for all injuries).(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Neurological recovery, mortality and length of stay after acute spinal cord injury associated with changes in management.
Based on epidemiological data from two populations of patients with acute spinal cord injury (ASCI), three outcome measures were compared to evaluate the effectiveness of management of ASCI patients in a regional, specialized acute spinal cord injury unit (ASCIU). The two populations consisted of a pre-ASCIU group of 351 patients managed from 1947-73 before the establishment of the ASCIU, and an ASCIU group of 201 patients managed in an ASCIU from 1974-81. The three outcome measures were mortality rate, length of stay (LOS) during first hospitalization, and neurological recovery. Linear regression and multiple regression analyses were used to determine whether differences in the outcome measures were attributable to differences in admission variables in addition to the influence of the ASCIU. The results showed that the patients treated in the ASCIU had a significant reduction in the mortality rate of almost 50% (P = 0.022), a significant reduction in the LOS of almost 50% (P < 0.001), and a significant increase in neurological recovery consisting of a doubling of the neurological recovery scale utilized (P < 0.001). Multiple regression analysis showed that the reduction in mortality rate was significantly influenced by differences in the admission variables between the two groups. However, the establishment of the ASCIU was associated with a significant reduction in LOS and a significant improvement in neurological recovery. Thus, these results support the view that management of ASCI patients in a regional, multidisciplinary unit is medically advantageous and can reduce the LOS.
Acute Disease↗
Update on the pathophysiology and pathology of acute spinal cord injury.
There is evidence from both clinical and experimental studies that the spinal cord suffers both primary and secondary damage after acute spinal cord injury. The pathophysiology of secondary injury involves a multitude of cellular and molecular events which progress over the first few days after injury, the most important of which are systemic and local vascular insults, electrolyte shifts, oedema and excitotoxicity. These secondary processes contribute to the evolution of the pathological changes which in the severe injuries progress from central haemorrhagic necrosis involving mainly the grey matter to infarction of both the white and grey matter at the injury site and for a considerable distance proximally and distally. Less severe injuries show a variety of axonal and myelin changes. The concept of secondary injury is consistent with the results of therapeutic approaches to improve outcome.
Acute Disease↗
C1-C2 posterior cervical fusion: long-term evaluation of results and efficacy.
Posterior wiring techniques are the most commonly used methods of achieving C1-C2 arthrodesis. Recently, transarticular screw fixation and interlaminar clamping have been advocated to achieve more secure fixation. A retrospective review of patients undergoing C1-C2 fusion for nonneoplastic disease was undertaken at the University of Toronto Hospital, with the aim of determining the long-term outcome of the selected procedures. Thirty-two patients underwent 36 procedures from 1986 to 1992, with a mean follow-up of 4.7 +/- 2.2 years (range, 2.0-8.0 yr). The most common disease processes were odontoid fracture (18 patients), transverse atlantal ligament injury (5 patients), os odontoideum (5 patients), and rheumatoid C1-C2 instability (3 patients). Thirty-one Gallie fusions, one Brooks-Jenkins fusion, two transarticular screw fusions, and two Halifax clamp applications were performed. Six (19%) of Gallie/Brooks-Jenkins fusions failed. These occurred with os odontoideum (three patients), Type II odontoid fracture (two patients), and transverse atlantal ligament injury (one patient). All transarticular screw and Halifax clamp procedures resulted in successful fusions. Two procedures (6%) resulted in new neurological deficit; both of these patients underwent posterior wiring for os odontoideum. This study suggests that Type II odontoid fractures may be successfully managed by a posterior wiring technique alone. Rheumatoid C1-C2 instability may be managed by posterior wiring supplemented with halo immobilization. Transarticular screw fixation has several potential advantages as a technique for C1-C2 arthrodesis and, in particular, may be appropriate for os odontoideum that had a high failure rate (75%) with conventional posterior wiring, even when this was supplemented with halo bracing.
Adolescent↗
Spontaneous meningocele, a rare middle ear mass.
This report describes the CT and MR findings in one patient with a spontaneous middle ear meningocele and a second patient with a middle ear meningoencephalocele possibly related to a large intracranial mass. High-resolution CT defined anatomic relation and bone destruction, and MR aided in tissue characterization.
Adult↗
Persistence of rubrospinal projections following spinal cord injury in the rat.
Recent neurophysiological and magnetic resonance imaging studies of clinically "complete" human spinal cord injuries indicate that some patients have considerable subclinical function and substantial morphological integrity of descending spinal tracts. In contrast, extensive histopathological changes, including cell death, have been described in central nervous system nuclei projecting to the cord following experimental transection or hemisection of the spinal cord in animal models. We have used a rodent model of severe compression cord injury that more closely resembles the clinical pathophysiology to investigate the extent of the persistence of the rubrospinal projection. Counts of red nucleus neurons retrogradely labelled with Fluorogold demonstrate that in contrast to the results obtained with transection models, compression injuries of the spinal cord do not result in massive loss of rubrospinal projections, at least up to 8 weeks postinjury. The results also suggest that many of the axons persist distal to the lesion site and that they are functionally intact with respect to retrograde transport capabilities.
Animals↗
Mechanism of action and persistence of neuroprotection by cell-permeant Ca2+ chelators.
Cell-permeant Ca2+ chelators such as 1,2-bis-(2-aminophenoxy)ethane- N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) have been reported to protect neurons in experimental focal cerebral ischemia. However, their in vivo actions are uncertain, and their protective efficacy is proven only in brief cerebral ischemia paradigms. Here we examine their mechanism of action in vitro and duration of efficacy in vivo. Electrophysiological studies were made in CA1 neurons in rat hippocampal slices. When superfused with BAPTA-AM (30-50 microM), CA1 somatic field potential recordings showed attenuation of the population spike amplitude, and intracellular recordings showed reduced excitatory postsynaptic potentials, indicating inhibition of excitatory synaptic transmission. Also, Ca(2+)-dependent accommodation and post-spike-train hyperpolarizations were reduced, indicating Ca2+ chelation hear the internal cell membrane surface. To determine whether Ca2+ chelators reduce the size of cerebral infarction rather than simply delaying its evolution, we studied the effects of BAPTA-AM treatment on infarction size 24 h after permanent middle cerebral artery occlusion. Fischer rats (n = 8 per group) were pretreated with saline, BAPTA-AM (20 mg/kg), or MK-801 (0.5 mg/kg). Infarction volumes in animals treated with BAPTA-AM were reduced by 50.5% compared with controls (p = 0.018), whereas animals treated with MK-801 experienced a statistically insignificant infarct volume reduction (26%; p = 0.27). These data show a persistence of neuroprotection by the Ca2+ chelator at 24 h and indicate that it may act by attenuating synaptic transmission and subplasma membrane Ca2+ excess.
Animals↗
Properties of neuroprotective cell-permeant Ca2+ chelators: effects on [Ca2+]i and glutamate neurotoxicity in vitro.
1. Cell-permeant Ca2+ chelators such as 1,2-bis-(2-amino-phenoxy)ethane- N,N,N',N'-tetraacetic acid acetoxymethyl ester (BAPTA-AM) protect neurons against excitotoxic and ischemic neuronal injury in vitro and in vivo. Here we provide the first steps toward characterizing the mechanisms by which these agents produce their neuroprotective effects. 2. Cultured mouse spinal neurons were simultaneously loaded with the Ca2+ indicator fura-2 and with one of three permeant chelators derived from the fast Ca2+ buffer BAPTA, or with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid acetoxymethyl ester (EGTA-AM). Adding these chelators did not interfere with the fluorescence spectrum of fura-2 and had no effect on baseline [Ca2+]i. 3. The neurons were challenged with 250 microM L-glutamate for 50 min, producing a marked transient [Ca2+]i increase followed by a decay of [Ca2+]i to a lower "plateau." About 80% of control neurons succumbed to this excitotoxic insult. Neurons that survived adjusted their plateau [Ca2+]i to lower levels than those that succumbed. 4. Neurons that were pretreated with permeant Ca2+ chelators became more resistant to these neurotoxic challenges. 5. We examined whether this reduction in glutamate neurotoxicity could be related to the given buffer's known Ca2+ affinity (Kd), its Ca2+ binding kinetics, and its ability to attenuate glutamate-induced [Ca2+]i increases. 6. Pretreatment of neurons with BAPTA analogues having Kds ranging from 100 to 3,600 microM 1) attenuated the amplitude and 2) lengthened the time constant describing the rise and decay of the glutamate-evoked [Ca2+]i transient. The magnitude of these effects paralleled the affinity of the chelator for Ca2+. 7. BAPTA-AM and its analogues dramatically attenuated the early neurotoxicity of glutamate, reducing cell deaths by up to 80%. However, in contrast with the graded effects of chelators having different Ca2+ affinities on Ca2+ transients, all BAPTA analogues were equally protective. These protective effects did not relate to the chelators' Ca2+ affinity within a Kd range of 100 nM (for BAPTA) to 3,600 nM (for 5,5'-dibromo BAPTA). 8. BAPTA-AM protected neurons in a concentration-dependent manner with 50% protection obtained with 10 microM, a concentration having no effect on the [Ca2+]i transient amplitude. 9. EGTA, a slow Ca2+ buffer with a similar Ca2+ affinity to BAPTA produced the same effects as BAPTA on [Ca2+]i transient kinetics. However, it was far less protective than BAPTA. 10. The time course of early glutamate neurotoxicity was altered by the BAPTA analogues, but not EGTA. BAPTA analogues caused a small increase in cell deaths in the first minutes of each experiment, followed by relative sparing from further neurodegeneration. 11. The ability of low Ca2+ affinity chelators such as 5,5'-dibromo BAPTA to protect neurons without markedly attenuating measured [Ca2+]i increases conflicts with the hypothesis that global elevations in [Ca2+]i are responsible for triggering neurotoxicity.(ABSTRACT TRUNCATED AT 400 WORDS)
Animals↗
Characterization of longitudinal field gradients from electrical stimulation in the normal and injured rodent spinal cord.
The purpose of this experiment was to characterize the longitudinal field gradients from exogenously applied electrical stimulation in the normal and injured rodent spinal cord. In addition, we compared the field gradients arising from stimulation with two different types of stimulating electrodes. Twenty normal rats underwent the surgical implantation of either extradural disc (n = 10) or cuff (n = 10) electrodes in the lower cervical and upper thoracic spinal cord. Sine waves of 1.5 to 50 microA and 0.5 to 50 Hz were used for stimulation. Field gradients were measured differentially from two extracellular glass microelectrodes, positioned stereotactically in the spinal cord at different locations between the stimulating electrodes. The effect of acute spinal cord injury on local field strength was studied in five animals from each group. The field gradients from stimulation with disc electrodes were greatest in close proximity to the discs and decreased markedly toward the point equidistant between the electrodes. In contrast, the gradients produced by cuff electrodes were much more evenly distributed along the spinal cord, increasing only slightly in proximity to the electrodes. These fields were also more evenly distributed throughout the spinal cord in cross-section but were generally weaker than those arising from disc electrodes. Acute spinal cord injury significantly increased the field gradients arising from both disc and cuff electrodes. However, the observed gradients remained substantially lower than those reported to enhance neurite growth in vitro. We conclude that the position and design of stimulating electrodes has a profound effect on longitudinal field gradients within the mammalian spinal cord, as does the presence of an acute spinal cord injury.
Animals↗
Embolization with temporary balloon occlusion of the internal carotid artery and in vivo proton spectroscopy improves radical removal of petrous-tentorial meningioma.
A highly vascular petroclival meningioma supplied by tentorial branches of the internal carotid artery was embolized by temporary balloon occlusion of the parent vessel distal to the tumor, followed by obliteration of the tumor vascularity with polyvinyl alcohol particles. Subsequently, in vivo proton spectroscopy showed necrosis of a large portion of the tumor and helped determine the timing of surgery. Both innovative techniques considerably facilitated the subsequent radical excision of the tumor with no neurological morbidity.
Adult↗
Vestibular schwannoma (acoustic neuroma): the profession is not achieving its potential for early diagnosis.
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Evoked Potentials, Auditory, Brain Stem↗
Secondary Ca2+ overload indicates early neuronal injury which precedes staining with viability indicators.
Spinal neurons, lethally challenged with excitatory amino acids (EAAs) or with high-K+, underwent a biphasic rise in free intracellular calcium concentration ([Ca2+]i). In contrast to the initial rise in [Ca2+]i which recovered, the secondary, irreversible [Ca2+]i increase was unaffected by antagonists of EAA receptors or Ca2+ channels. Also, it correlated highly with cell death, but preceded vital staining with trypan blue and ethidium homodimer, reflecting damaged cellular Ca2+ regulation rather than plasma membrane leakiness. Our findings suggest that delayed Ca2+ overload is the end-product rather than the cause of Ca(2+)-triggered neurotoxic processes.
Amino Acids↗
Effect of nimodipine or methylprednisolone on recovery from acute experimental spinal cord injury in rats.
The purpose of the present study was to examine the behavioral, electrophysiologic, and anatomic responses to nimodipine or methylprednisolone treatment of acute experimental spinal cord injury. Four groups of rats were injured at T1 by compressing the cord with a 52-g clip for 1 minute. The treatments were begun 15 minutes after injury, and the animals were observed thereafter for 8 weeks. Nimodipine 0.02 mg/kg/h intravenously (iv) for 8 hours with adjuvant albumen volume expansion, followed by 20 mg/kg nimodipine enterally three times per day for 7 days, produced a moderately better composite score comprising four endpoint parameters than the other treatments which consisted of nimodipine iv for 8 hours only, methylprednisolone 30 mg/kg iv bolus followed by 5.4 mg/kg/h iv for 8 hours, or control.
Acute Disease↗
Changes in epidemiology of acute spinal cord injury from 1947 to 1981.
The aim of this study was to determine whether there have been epidemiologic changes in acute spinal cord injury. Two groups of patients injured in the same geographic area were compared: the first group of 351 patients was injured between 1947 and 1973; and the second group of 201 patients between 1974 and 1981. The results showed that there were indeed major epidemiologic changes in spinal cord injury between the two study periods. Most importantly, the more recently injured group were younger, arrived sooner, had less severe cord injuries, and higher frequencies of motor vehicle, and sports and recreational accidents, but fewer work-related injuries.
Accidents↗
An in vivo technique for 3-dimensional field mapping in the rodent spinal cord.
The purpose of this investigation was to develop a reliable method for in vivo mapping of small exogenously applied electrical fields in the mammalian spinal cord. Experiments were performed in vitro to validate the technique in addition to recordings made in vivo on normal and spinal cord injured rats. Sine waves of 1.5-50 microA and 0.5-50 Hz were used for stimulation. Field gradients were measured with a lock-in differential amplifier. Glass recording micro-electrodes were used for in vivo experiments. The accuracy of the technique was found to be highly dependent on the waveform of the current and impedance matching between the recording electrodes. Recordings made in vivo demonstrated that measured fields were linearly related to the intensity of stimulation. Field gradients were not influenced by stimulation frequencies of 5-50 Hz. Estimates were made of the influence of the surgical exposure on the measured gradients. Our results demonstrate that small electrical fields can be accurately mapped in vivo and interpolated throughout a broad range of intensities and frequencies.
Animals↗
Cell-permeant Ca2+ chelators reduce early excitotoxic and ischemic neuronal injury in vitro and in vivo.
We report the characterization of the first successful treatment of neuronal ischemic injury in vivo by cell-permeant Ca2+ chelators. The chelators attenuated glutamate-induced intracellular Ca2+ increases and neurotoxicity in neuronal explant cultures. When infused intravenously in rats, permeant fluorescent BAPTA analogs accumulated in neurons in several brain regions. BAPTA-AM, infused in vivo, reduced Ca(2+)-dependent spike frequency adaptation and post-spike train hyperpolarizations in CA1 neurons taken from treated animals. This effect was reproduced by direct injections of BAPTA into untreated neurons. The effects of three different chelators (BAPTA, 5,5'-difluoro BAPTA, and 4,4'-difluoro BAPTA) on Ca(2+)-dependent membrane excitability varied with their Ca2+ affinity. When the chelators' permeant forms were used to treat rats prior to the induction of focal cortical ischemia, they were highly neuroprotective, as gauged by significant reductions in cortical infarction volumes and neuronal sparing. The chelators' protective effects in vivo also reflected their affinity for Ca2+. This report provides the most direct evidence to date that intracellular Ca2+ excess triggers early neurodegeneration in vivo and contributes a novel therapeutic approach to neuronal ischemia of potential clinical utility.
Animals↗