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PubMed2006

Increased spinal c-Fos expression with noxious and non-noxious peripheral stimulation after severe spinal contusion.

The effects of severe contusive spinal cord injury (SCI), at thoracic level 8 (T8), on lumbar c-Fos expression in the spinal cord was investigated. As hypothesized, chronic SCI has a significant effect on expression of c-Fos in the dorsal spinal sensory areas with noxious and innocuous peripheral stimulation of the sciatic nerve. This alteration to stimulation effects was measured using counts of c-Fos immunoreactive cells in the dorsal horn of the L5 lumbar spinal cord in injured animals at 90 days post-injury and in uninjured controls. The number of c-Fos immunoreactive cells increased in SCI rats only after noxious peripheral stimulation (electrical and chemical) suggesting a general increase in excitability in spinal pathways (central sensitization) associated with chronic SCI. These altered responses may represent a functional anatomical reorganization of spinal cord circuitry leading to increased dorsal horn c-Fos expression as a response to severe chronic contusive damage to the spinal cord sensory pathways.

Animals↗
PubMed2001

Responses of spinal neurones to cutaneous and dorsal root stimuli in rats with mechanical allodynia after contusive spinal cord injury.

The firing of neurones in spinal segments adjacent to a contusive T13 spinal cord injury was characterised in anaesthetised rats. Three groups of rats were examined: (1) allodynic spinally injured, (2) non-allodynic spinally injured and (3) normal, uninjured. Spinal cord field potentials evoked by electrical dorsal root stimulation and the responses of 207 dorsal horn neurones to mechanical stimuli applied to the skin were studied. Within the lesioned spinal segment few active neurones were encountered and field potentials were absent. Depolarising field potentials recorded rostral to the lesion were reduced in both allodynic and non-allodynic animals compared to uninjured controls, while those recorded in caudal segments were enhanced in allodynic animals. Neuronal recordings revealed that allodynia was associated with exaggerated responses, including afterdischarges, to innocuous and noxious mechanical stimuli in a proportion of wide dynamic range, but not low threshold, neurones. These changes were observed both rostral and caudal to the site of injury. The results suggest that an increased responsiveness of some dorsal horn neurones in segments neighbouring a contusive spinal cord injury may contribute to the expression of mechanical allodynia. It is proposed that a relative lack of inhibition underlies altered cell responses.

Animals↗
PubMed2002

Effects of antioxidant, OPC-14117, on secondary cellular damage and behavioral deficits following cortical contusion in the rat.

In the present study, we examined the effects of OPC-14117, a superoxide radical scavenger, on the secondary cellular damage and cognitive dysfunction occurring in a rat model of cerebral contusion induced by a controlled cortical impact (CCI). Histological examinations revealed that the contusion necrosis volume reached 13.6+/-5.3 mm(3) in non-treated animals and declined to 1.9+/-0.6 mm(3) in OPC-14117-treated animals (P<0.01). The cell number of the CA3 region was 120.0+/-12.4 cells/mm in the normal controls, 73.6+/-9.9 cells/mm in the non-treated animals, and 111.2+/-10.2 cells/mm in the OPC-14117-treated animals, indicating that CCI-induced selective neuronal cell death in the CA3 region was attenuated by the OPC-14117 administration (P<0.01). The tissue osmolality, as determined with a vapor pressure osmometer, was 314.5+/-15.4 mmol/kg in the normal brain and increased to 426.0+/-20.1 mmol/kg at 12 h following CCI. The increase in tissue osmolality was significantly attenuated by OPC-14117 administration (P<0.01). The OPC-14117 administration also attenuated the CCI-induced cognitive deficits. The OPC-14117-treated animals showed a tendency to improve on the Morris water maze performance test. The impairment of the habituation of exploratory activity elicited by CCI was significantly attenuated by OPC-14117 administration (P<0.05). In conclusion, OPC-14117 may have a potential for decreasing secondary cellular damage due to traumatic brain injury since it is as efficacious as any other compound tested in this model.

Animals↗
PubMed2003

Gene transfer of glial cell line-derived neurotrophic factor promotes functional recovery following spinal cord contusion.

Neuronal cell death and the failure of axonal regeneration cause a permanent functional deficit following spinal cord injury (SCI). Administration of recombinant glial cell line-derived neurotrophic factor (GDNF) has previously been reported to rescue neurons following severe SCI, resulting in improved hindlimb locomotion in rats. In this study, thus, GDNF gene therapy using an adenoviral vector (rAd-GDNF) was examined in rats following SCI induced by dropping the NYU weight-drop impactor from a height of 25 mm onto spinal segment T9-T10. To evaluate the efficacy of intraspinal injection of recombinant adenovirus into the injured spinal cord, we observed green fluorescent protein (GFP) gene transfer in the contused spinal cord. GFP was effectively expressed in the injured spinal cord, and the most prominently transduced cells were astrocytes. The expression of GDNF was detected only in rats receiving rAd-GDNF, not the controls, and remained detectable around the injured site for at least 8 days. Open-field locomotion analysis revealed that rats receiving rAd-GDNF exhibited improved locomotor function and hindlimb weight support compared to the control groups. Immunohistochemical examination for the neuronal marker, calcitonin gene-related peptide (CGRP), showed an increase in CGRP+ neuronal fibers in the injured spinal cord in rats receiving rAd-GDNF treatment. Collectively, the results suggest that adenoviral gene transfer of GDNF can preserve neuronal fibers and promote hindlimb locomotor recovery from spinal cord contusion. This research should provide information for developing a clinical strategy for GDNF gene therapy.

Adenoviridae↗
PubMed2004

Development of glioblastoma multiforme following traumatic cerebral contusion: case report and review of literature.

BACKGROUND: Diagnostic criteria for posttraumatic brain tumors were formulated in the pre-CT (computerized tomography) era. We propose that radiologic criteria incorporating imaging data be added to the existing criteria. CASE DESCRIPTION: We report a case of a 56-year-old man who presented with history of raised intracranial pressure of 20 days' duration. Imaging showed a large left frontal intra-axial mass lesion. He had history of head injury 5 years prior with CT evidence of bilateral basifrontal contusions. There was no contrast enhancement at the site of the contusions in an intervening CT scan done 18 months after the trauma. He underwent radical excision of the mass, and the histopathology was reported as glioblastoma multiforme. We formulated additional radiologic criteria for tumors that may present following trauma. A review of the literature of posttraumatic gliomas is also presented. CONCLUSION: Fulfillment of the additional radiologic criteria proposed by us will help distinguish a tumor that developed following trauma from that which was present before the occurrence of the injury.

Accidents, Traffic↗
PubMed1984

The use of gated radionuclide angiography in the diagnosis of cardiac contusion.

No currently used diagnostic test is an accurate predictor of patients who will develop morbidity or mortality from cardiac contusion. In a prospective study we used gated cardiac radionuclide angiography to assess cardiac function in 30 patients with blunt chest trauma, and we compared the results of this test with those of other diagnostic studies for cardiac contusion to determine whether gated angiography is a more accurate predictor of serious cardiac injury. Diagnostic tests included the following: serial electrocardiograms (ECG), serial creatine phosphokinase muscle-brain isoenzyme (CPK-MB) and lactic dehydrogenase (LDH) isoenzymes, gated cardiac radionuclide angiography, and technetium-99m (Tc-99m) pyrophosphate scintigraphy. Abnormal studies were present in 26 patients; 22 showed abnormalities in CPK-MB, 19 on ECG, and five on gated scan. No patient demonstrated an abnormal Tc-99m pyrophosphate scan or abnormal elevation of LDH isoenzyme. Although no diagnostic test was predictive of morbidity and mortality, CPK-MB isoenzyme was the only test to correlate with morbidity and mortality. Morbidity and mortality correlated most closely with the number of associated major injuries and the presence of hypotension or hypoxia.

Adolescent↗
PubMed1988

Value of creatine phosphokinase isoenzyme determinations in the diagnosis of myocardial contusion.

Myocardial contusion is an injury often missed in the patient with severe multisystem trauma. Fifty patients with physical findings or mechanisms of injury that were suggestive of possible nonpenetrating injury to the heart were studied with serial creatine phosphokinase isoenzyme (CPK/MB), continuous arrhythmia monitoring, and ECGs for at least 72 hours. Two-dimensional echocardiograms were obtained on all patients within 48 hours of admission. Seventy-two percent (36 of 50) had detectable CPK/MB. Ten patients had echocardiograms suggestive of cardiac contusion. Of these ten, three had no detectable CPK/MB and six had CPK/MB of less than 5%. CPK/MB had a sensitivity of 70% and a specificity of 27.5%. We conclude that in the patient with multisystem injury, CPK/MB determinations are not reliable. The decision to evaluate the patient with echocardiography should be made on the basis of physical findings and, more importantly, on mechanism of injury.

Adolescent↗
PubMed1977

Cardiac contusion and right bundle branch block.

In a case of transient right bundle branch block due to nonpenetrating chest trauma, this abnormal electrocardiographic finding was the sole manifestation of cardiac contusion. There is a high frequency of occult cardiac contusion and routine electrocardiography is recommended in the evaluation of nonpenetrating chest trauma.

Adult↗
PubMed2003

Significant elevation of urinary trypsin inhibitor in patients with brain contusion--a preliminary report.

Urinary trypsin inhibitor (UTI) is a protease inhibitor, which is produced in the liver. The correlation between UTI level and head injury has not been evaluated. This study was designed to investigate UTI levels in patients with severe head injury. We measured UTI in the urine of patients with brain contusion. UTI was significantly higher in those patients compared to the control group. The results suggest that UTI may be useful for assessing the severity of head injury and also as a treatment marker in patients with brain contusion.

Adult↗
PubMed2006

F-wave amplitudes indicate evolving spinal autonomy during spontaneous recovery of hindlimb function in rat spinal cord contusion.

STUDY DESIGN: Experimental rat model of spinal cord contusion. OBJECTIVES: To reveal the extent of spinal autonomy contributing to recovery of hindlimb function. SETTING: Experimental laboratory of a neurosurgical university department. METHODS: F-wave amplitudes as a probe for spinal cord excitability were recorded from both sciatic nerves (lumbar segments L2-L5) before and after an experimental spinal cord contusion performed in the lower thoracic spinal cord. Additionally, transcranial electrically motor evoked potentials from the hindlimbs and cerebral somatosensory potentials evoked by sciatic nerve stimulation were recorded. Clinical evaluation of hindlimb function was done regularly for survival periods of 3 and 50 days, respectively. Electrophysiological testing was performed immediately prior and after lesioning of the cord and at the endpoint of survival periods. RESULTS: Hindlimb function recovered from a mean Basso-Beattie-Bresnahan score of 5.6 on day 1 to 9.2 on day 3 (3-day-survivors) and from 7.7 to 17.2 on day 50 (50-day-survivors). This was accompanied by a significant increase of F-wave amplitudes on day 50 compared to baseline values, whereas amplitudes of somatosensory and motor-evoked potentials remained significantly depressed. CONCLUSION: Recovery of hindlimb function may at least in part be attributed to evolving spinal autonomy, which can be assessed by F-wave amplitudes.

Action Potentials↗
PubMed2006

Subacute human spinal cord contusion: few lymphocytes and many macrophages.

STUDY DESIGN: Clinicopathological correlation of three cases of subacute cervical spinal cord contusions. OBJECTIVE: To correlate the pathology of subacute cervical spinal cord injury (SCI) with imaging and clinical-functional studies, and to compare with findings from previous human SCI studies and animal models of SCI. SETTING: Department of Pathology, SUNY-Upstate Medical University, Syracuse, NY, USA. METHOD: Post mortem pathology report. CASE REPORT/RESULTS: The clinical, radiological, and pathological findings of three cases of subacute spinal cord contusions are described in detail. The postinjury survival periods were 15, 20, and 60 days, respectively. Extensive microglia/macrophage infiltrations without significant lymphocytes are seen in all cases. Free radical injury as assessed by immunocytochemistry for 4-hydroxynonenal and nitrotyrosine showed a labeling pattern parallel to that of the macrophage distribution at 15 days, but no significant labeling in the injury sites at 20 and 60 days. CONCLUSION: The present report, though limited in sample size, shows plenty of activated microglia/macrophages in human SCI up to 60 days postinjury. This observation not only confirms similar findings in previous studies, but also raises an intriguing question of potential interactions between these activated microglia/macrophages and the experimental therapy, proposed by some authors, of injecting exogenously activated macrophages to promote SCI repair. The small number of human SCI cases (in this as well as in most other single medical centers) available for detailed study illustrates the need for the establishment of a consortium of human SCI tissue banks.

Aged, 80 and over↗
PubMed2000

[Left ventricular aneurysm after myocardial contusion caused by blunt chest trauma].

A 30-year old male car-driver was polytraumatized after a frontal collision with another motor vehicle (left-sided rib fractures, right-sided pneumothorax, multiple lung contusions, anterior and posterior pelvic ring fracture, femoral shaft fracture, traumatic subarachnoid hemorrhage. After intubation and hemodynamic stabilization on the scene of accident, he was transported to our institution. Transesophageal echocardiography revealed a left-ventricular anteroseptal akinesia and patchy intramyocardial hyperdensities as indicator of myocardial contusion which was confirmed later by autopsy. In the further course, the patient developed an anteroseptal aneurysm with severe left ventricular dysfunction nad episodes of arrhythmias. Finally, septic shock complicated the case and the patient died 30 days of intensive care from therapy-refractory multiple organ system failure.

Accidents, Traffic↗
PubMed2004

Mechanical and cold allodynia in a rat spinal cord contusion model.

This study examined the time course of mechanical and cold allodynia in rat hindpaw after spinal cord contusion. Hindpaw withdrawal threshold to graded von Frey hair stimulation and withdrawal frequency to acetone application were measured in rats subjected to contusions of varying severity, produced by a MASCIS impactor device with a 10 g weight dropped from 6.25, 12.5, or 25 mm. Mechanical and cold allodynia developed following the injury, and differences in the incidence of allodynia and in withdrawal threshold were significant among these groups. The least severe injury (6.25 mm) most consistently caused a decreased hindpaw threshold to mechanical stimulation and an increased withdrawal frequency to cold.

Animals↗
PubMed2002

Velocity-dependent ankle torque in rats after contusion injury of the midthoracic spinal cord: time course.

Progressive neurophysiological changes in the excitability of the pathways that subserved ankle extensor stretch reflexes were observed following midthoracic contusion. The purpose of the present study was to determine the nature and time course of velocity-dependent changes in the excitability of the ankle stretch reflex following T(8) contusion injury. These studies were conducted in adult Sprague-Dawley rats using a 10-g 2.5-cm weight drop onto the exposed thoracic spinal cord (using an NYU injury device and a MASCIS protocol). Velocity-dependent ankle torques and triceps surae EMGs were measured in awake animals over a broad range of rotation velocities (49-612 deg/sec) using instrumentation and protocol previously reported. EMGs and ankle torques were measured before and at weekly intervals following injury. Statistical tests of the data included within group repeated measures ANOVA and between group one-way ANOVA comparisons with time-matched control animals. An alternating pattern of significant increase followed by significant decrease in velocity-dependent ankle torque was observed during the first postinjury month. An increase of 33% in the peak torque and 24% in peak EMG magnitude at 612 deg/sec was observed in the first week. EMG burst amplitudes, that were timed-locked to the dynamic phase of the rotation, were observed to increase and decrease in a manner, which indicated that the changes in torque included stretch-evoked active contractions of the ankle extensors. During the second and third postinjury months, consistent 24-40% increases in the peak torques and 17-107% increases in the EMG magnitudes at the highest velocity were observed. No significant increases in torques were observed in the slowest rotation velocity in these periods.

Animals↗
PubMed2003

Effect of decompression craniotomy on increase of contusion volume and functional outcome after controlled cortical impact in mice.

If, how, and when decompressive craniotomy should be used for the treatment of increased intracranial pressure after traumatic brain injury are widely discussed clinical subjects. Despite the large number of clinical studies addressing this issue, experimental evidence of a beneficial or detrimental role of decompressive craniotomy after brain trauma is sparse. Therefore, we investigated the influence of craniotomy on intracranial pressure, contusion volume, and functional outcome in a model of traumatic brain injury in mice. Male C57/Bl6 mice were craniotomized above the right parietal cortex and were subjected to controlled cortical impact injury. In control mice, the craniotomy was closed immediately after trauma, whereas in treated animals the craniotomy was left open. In control mice intracranial pressure (ICP) increased to a maximum of 23.7 +/- 3.1 mm Hg 6 h after trauma (p < 0.001), while in craniotomized animals, no ICP increase was observed. Twenty-four hours after trauma, the point in time of maximal lesion expansion, contusion volume in craniotomized mice was 40% smaller as compared to controls (18.3 +/- 2.0 vs. 30.2 +/- 3.5 mm(3), p < 0.04). Furthermore, craniotomized mice showed significantly improved motor function in a beam walking task (p < 0.04) and faster recovery of body weight after trauma (p < 0.02). Our results demonstrate that craniotomy blunts post-traumatic ICP increase, significantly reduces secondary brain damage and improves functional outcome after experimental TBI. Careful clinical evaluation of craniotomy as a therapeutic option after TBI in man may therefore be indicated.

Animals↗
PubMed1995

Blood-brain barrier breakdown and edema formation following frontal cortical contusion: does hormonal status play a role?

The present experiment was designed to evaluate and correlate the time course of blood-brain barrier (BBB) integrity and cerebral edema in adult male rats given medial frontal cortex contusions. The effect of sex hormones on BBB integrity in the same injury model was also examined, because previous work has shown that progesterone can reduce cerebral edema (Roof et al., 1993). BBB breakdown was assessed by Evans blue extravasation and albumin immunostaining while edema formation was measured by the wet weight dry weight technique. These processes were examined beginning 2 h and continuing up to 10 days after injury. Our findings show that medial frontal contusion in rats produces changes in cerebral water content and opening of the BBB that endures at least 7 days postinjury. Although pseudopregnancy has been shown to reduce cerebral edema at day 1 postinjury, we did not find any evidence that this hormonal state is associated with BBB repair.

Animals↗
PubMed2000

Traumatic spinal cord injury produced by controlled contusion in mouse.

Previous work from this laboratory has described a rat spinal cord injury (SCI) model in which the mid-thoracic spinal cord is subjected to a single rapid and calibrated displacement at the site of a dorsal laminectomy. Injury is initiated at the tip of a vertical shaft driven by an electromagnetic shaker. Transducers arranged in series with the shaft record the patterns of displacement and force during the impact sequence. In the present study, this device and the relevant surgical procedures were adapted to produce a spinal contusion injury model in laboratory mice. The signal generator for the injury device has also been converted to a computer-controlled interface to permit extension of the model to other laboratories. Mice were subjected to SCI across a range of severities by varying the amplitude of displacement and the magnitude of measured preload force on the dural surface. A moderate injury produced by displacement of 0.5 mm over 25 msec resulted in initial paralysis and recovery of locomotion with chronic deficits in hindlimb function. The magnitude of the peak force, impulse, power, and energy generated at impact were correlated with behavioral outcome at 1 day postinjury, while peak displacement and impulse were the best predictors of behavioral outcome at 28 days postinjury. The shape of the force recording proved to be a highly sensitive measure of subtle variations in the spinal compartment that were otherwise difficult to detect in this small species. The results demonstrate that the electromagnetic spinal cord injury device (ESCID) can be used to produce a well-controlled contusion injury in mice. The unique features of controlled displacement and monitoring of the biomechanical parameters at the time of impact provide advantages of this model for reducing outcome variability. Use of this model in mice with naturally occurring and genetically engineered mutations will facilitate understanding of the molecular mechanisms of pathophysiology following traumatic spinal cord injury.

Animals↗
PubMed2004

The mitochondrial uncoupling agent 2,4-dinitrophenol improves mitochondrial function, attenuates oxidative damage, and increases white matter sparing in the contused spinal cord.

The purpose of this study was to investigate the potential neuroprotective efficacy of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in rats following a mild to moderate spinal cord contusion injury. Animals received intraperitoneal injections of vehicle (DMSO) or 5 mg/mL of DNP prior to injury. Twenty-four hours following surgery, mitochondrial function was assessed in mitochondria isolated from spinal cord synaptosomes. In addition, synaptosomes were used to measure indicators of reactive oxygen species formation, lipid peroxidation, and protein oxidation. Relative to vehicle-treated animals, pretreatment with DNP maintained mitochondrial bioenergetics and significantly decreased reactive oxygen species levels, lipid peroxidation, and protein carbonyl content following spinal cord injury. Furthermore, pretreatment with DNP significantly increased the amount of remaining white matter at the injury epicenter 6 weeks after injury. These results indicate that treatment with mitochondrial uncoupling agents may provide a novel approach for the treatment of secondary injury following spinal cord contusion.

2,4-Dinitrophenol↗