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PubMed1997

Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats.

Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.

Animals↗
PubMed1990

Blood-brain barrier damage in traumatic brain contusions.

Plasma proteins were used as an endogenous marker of blood-brain barrier damage in 19 patients dying with traumatic cortical contusions. Patients survived for a few hours to 31 days after head injury. Eight proteins (M WT 61-2,500 x 10(3) were demonstrated with standard immunohistochemical techniques. Proteins were not found in "control" brains or in macroscopically normal parasagittal cortex in the head injury patients. Proteins were found in all of the macroscopic contusion in all brains. Protein leakage appeared to be from the contusion itself. Protein staining around histologically normal vessels was unusual. There was a gradient of staining from the macroscopic contusion into the surrounding brain. There was a trend for staining to be most marked between 3 and 8 days survival after head injury. There was no gradient of leakage by molecular size of the protein.

Blood Proteins↗
PubMed1992

An immediate light microscopic response of neuronal somata, dendrites and axons to contusing concussive head injury in the rat.

Thirty-four rats were killed by transcardial perfusion fixation 1 min after a contusing concussive head injury, and 17 rats 1 day later. From the results obtained with a new silver method demonstrating traumatically damaged neuronal somata, dendrites and axons the following conclusions were drawn: (1) outside the contused territories all features of traumatically induced neuronal argyrophilia are similar to those found in non-contusing concussive head injury, as reported in an accompanying paper; (2) within contused territories the neuronal argyrophilia is abolished by some substance released either from damaged blood vessels or damage parenchymal cells, while the neuronal damage otherwise underlying the induction of argyrophilia is present; (3) different phenotypes of neurons are vulnerable to different values of the parameters of the intracranial pressure wave generated by the trauma; (4) some of the neurons may recover from the traumatically induced argyrophilic damage; (5) traumatically induced inundation of neurons with extracellular tracers, as reported by other authors, and somato-dendritic argyrophilia may be different manifestations of one and the same phenomenon; and (6) diffuse primary traumatic axonal injury in human neuropathology may be closely correlated to axonal argyrophilia.

Animals↗
PubMed1994

Induction of Cu,Zn-superoxide dismutase after cortical contusion injury during hypothermia.

To determine the effect of hypothermia on superoxide injury after cerebral contusion, the induction of Cu,Zn-superoxide dismutase was examined 6 h after contusion in rats using Northern blotting. Cu,Zn-superoxide dismutase gene expression increased at the periphery of the contusion, which may indicate the severity of the superoxide stimulus. This increase was preserved after contusion under hypothermia, which may show that superoxide injury is still severe although brain edema is decreased.

Animals↗
PubMed1994

Finite element analysis of cerebral contusion.

Finite element analysis was carried out to study the mechanism of cerebral contusion. Clinical findings indicate that most cerebral contusions in the absence of skull fracture occur at the frontal and temporal lobes. To explain these observations, cavitation and shear strain theories have long been advocated. Plane strain finite element models of a parasagittal section of the human head were developed in the present study. The model was first validated against a set of experimental results from the literature. Frontal and occipital impacts were then simulated, and pressure and shear stress distributions in the brain were compared. While comparable negative pressures always developed in the contrecoup regions, shear stress distributions remained nearly identical regardless of the impact direction, consistent with the clinically observed pattern for contusion. Therefore, shear strain theory appears to account better for the clinical findings in cerebral contusion.

Acceleration↗
PubMed2006

Cortical expression of nuclear factor kappaB after human brain contusion.

The aim of current study was to analyze the binding activity and the temporal and cellular expression of nuclear factor kappa B (NF-kappaB) in human contused brain. Eighteen contused brain samples were obtained from 17 patients undergoing surgery for brain contusions 5-80 h after trauma. NF-kappaB binding activity was detected by electrophoretic mobility shift assay (EMSA), and temporal and cellular expression of NF-kappaB subunits p65 and p50 was analyzed by immunohistochemistry. The results showed that a progressive upregulation of NF-kappaB activity occurred in the area surrounding the injured brain with the time from brain trauma to operation. The maximal expression of NF-kappaB was detected after 48 h postinjury. The expression of NF-kappaB p65 was mainly located at glial and vascular endothelial cells without expression at neurons. The expression of NF-kappaB p50 was mainly located at glial cells, a little at neurons and no expression at vascular endothelial cells. Within 24 h postinjury, both NF-kappaB p65 and p50 immunoreactivity was mainly observed in the nucleus of cells. After 24 h postinjury, NF-kappaB p65 labeling was found in the both nucleus and cytoplasm of glial and endothelial cells; otherwise, p50 labeling was primarily found in the nucleus of glial cells and in the nucleus, cytoplasm and process of neurons. It is concluded that NF-kappaB could be highly upregulated at human contused brain and the cellular pattern of p65 and p50 expression might be closely associated with the cell functions.

Adolescent↗
PubMed2006

Diverse morphological lesions and serious arrhythmias with hemodynamic insults occur in the early myocardial contusion due to blunt impact in dogs.

To investigate the morphology and hemodynamics of the early myocardial contusion, an animal model of cardiac contusion was established by impact to the precordial region at sternum at velocity of 10.0m/s with a mechanical elastic-cord propelled impactor in 19 dogs. The electrocardiogram and both the left and right intra-ventricular pressures were recorded continuously throughout the experiment. Histological and immunohistochemical examinations of myoglobin, creatine kinase-MB and fibrinogen were conducted. At the moment of impact, abrupt over-pressures within the left and right ventricles occurred with concomitant serious arrhythmias followed by variety of cardiac conduction disorders and depressed left and right ventricular systolic pressures during the observation times. Histologically, lesions of myocardial contusions were identified at subepicardial, myocardial or subendocardial layer as interstitial hemorrhage, disruption or coagulative necrosis as well as contraction band necrosis of the muscle fibers, which might be categorized into the hemorrhagic, necrotized and mixed forms. The three forms of lesions were found to exist independently, or co-existed in a heart. However, severity of the lesions varied greatly with different parts even within a heart. Intravascular thromboses were occasionally discovered post-impact. Immunohistochemically, loss of myoglobin and creatine kinase-MB from cardiac cells, and accumulation of fibrinogen at the cell membranes were detected 5min post-impact. The intracellular accumulation of fibrinogen increased with extension of post-impact intervals. Our results indicate that diverse morphological lesions concomitant with hemodynamic compromise and serious, even fatal arrhythmias occur in the early myocardial contusion, and intravascular thromboses are occasionally produced, suggesting that traumatic myocardial ischemic lesion may be induced due to blunt impact to the precordial region.

Animals↗
PubMed2006

A new model of upper cervical spinal contusion inducing a persistent unilateral diaphragmatic deficit in the adult rat.

Research on spinal cord trauma requires models reflecting the contusion mechanisms encountered in clinical situation. The aim of this study was to develop in the adult rat a reproducible model of upper cervical spinal cord contusion inducing persistent unilateral diaphragm deficit. After dura and pia matter removal, weight drop and compression were targeted at the ventro-lateral funiculi which contain the bulbospinal descending respiratory pathways that command the phrenic motoneurons innervating the diaphragm. At 7 days post-injury, the left diaphragm activity recorded in contused rats (27.4 +/- 5.1% of the contralateral activity) was significantly lower than in the sham group (97.6 +/- 1.2%). This respiratory deficit still persisted 1 month later. Histology showed a reproducible left C2-lateralized lesion that involved both white and gray matter including the ventro-lateral funiculi. This C2 contusion model provides a basis for testing both regenerative and neuroprotective strategies aimed at improving functional respiratory recovery after spinal cord trauma.

Animals↗
PubMedDate not supplied

Transplantation of oligodendrocyte precursors and sonic hedgehog results in improved function and white matter sparing in the spinal cords of adult rats after contusion.

BACKGROUND CONTEXT: A substantial cause of neurological disability in spinal cord injury is oligodendrocyte death leading to demyelination and axonal degeneration. Rescuing oligodendrocytes and preserving myelin is expected to result in significant improvement in functional outcome after spinal cord injury. Although previous investigators have used cellular transplantation of xenografted pluripotent embryonic stem cells and observed improved functional outcome, these transplants have required steroid administration and only a minority of these cells develop into oligodendrocytes. PURPOSE: The objective of the present study was to determine whether allografts of oligodendrocyte precursors transplanted into an area of incomplete spinal cord contusion would improve behavioral and electrophysiological measures of spinal cord function. Additional treatment incorporated the use of the glycoprotein molecule Sonic hedgehog (Shh), which has been shown to play a critical role in oligodendroglial development and induce proliferation of endogenous neural precursors after spinal cord injury. SETTING: Laboratory study. METHODS: Moderate spinal cord contusion injury was produced in 39 adult rats at T9-T10. Ten animals died during the course of the study. Nine rats served as contusion controls (Group 1). Six rats were treated with oligodendrocyte precursor transplantation 5 days after injury (Group 2). The transplanted cells were isolated from newborn rat pups using immunopanning techniques. Another eight rats received an injection of recombinant Shh along with the oligodendrocyte precursors (Group 3), while six more rats were treated with Shh alone (Group 4). Eight additional rats received only T9 laminectomies to serve as noninjured controls (Group 0). Animals were followed for 28 days. RESULTS: After an initial complete hindlimb paralysis, rats of all groups receiving a contusive injury recovered substantial function within 1 week. By 28 days, rats in Groups 2 and 3 scored 4.7 and 5.8 points better on the Basso, Beattie, Bresnahan (BBB) open field locomotor score than rats in group 1 (Groups 2 and 3=18.2 and 19.4 points, respectively, after 28 days vs. Group 1=13.6 points; p=.015). Rats in Group 4 scored no better than those in Group 1 (BBB=16.4). Motor evoked potential (MEP) recordings revealed a strong trend towards significant improvement in latency measurements in all treatment groups compared with controls at 28 days, although three animals in Group 1 and two animals in Group 3 were not recordable. Histological examination demonstrated significantly more spared white matter in the same groups that correlated with the improvements in BBB scores and MEP latencies. Immunohistochemical analysis showed the survival, proliferation and migration of the transplanted cells, as well as the induction of proliferating endogenous neural precursor cells in animals treated with Shh. CONCLUSIONS: These findings suggest that the transplantation of oligodendrocyte precursors may improve axonal conduction and spinal cord function in the injured spinal cord. The benefits seem more pronounced with the addition of Shh, and the addition of Shh alone results in the proliferation of an endogenous population of neural precursor cells.

Animals↗
PubMed1997

d-Amphetamine attenuates decreased cerebral glucose utilization after unilateral sensorimotor cortex contusion in rats.

Unilateral contusion injury to the sensorimotor cortex causes, among other symptoms, a transient contralateral hindlimb hemiparesis in rats. A single i.p. 2 mg/kg dose of d-amphetamine (d-AMPH) 24 h after injury accelerates spontaneous recovery from this particular deficit. The mechanism(s) of spontaneous and d-AMPH enhanced recovery are unknown but alleviation of a neuronal depression has been proposed. This quantitative CMRglu study was designed to determine effects of cortical contusion injury and d-AMPH on CMRglu in cortical and subcortical structures. At 2 days after injury, CMRglu was significantly reduced compared to sham-operated controls only in structures ipsilateral to contusion. Affected structures included the caudate putamen, medial geniculate nucleus, lateral geniculate nucleus and the parietal cortex immediately posterior to injury. By 6 days post-contusion, the hypometabolism partially reversed in all structures. A single low dose of d-AMPH significantly alleviated the post-traumatic CMRglu reduction at 2 days after injury. Importantly, while this alleviation was not significant for any single structure, the main effect of treatment was highly significant. d-AMPH increased CMRglu at 2 days post-injury by 18-33% compared to contused/saline-treated rats. These results suggest that alleviation of neuronal metabolic depression may contribute to spontaneous and d-AMPH enhanced recovery.

Animals↗
PubMed1991

[Myocardial contusions in closed thoracic injuries: a prospective study].

Various laboratory investigations were assessed with respect to their accuracy in detecting myocardial contusion in patients with blunt chest trauma. All patients, aged between 18 and 50 years, admitted to the intensive care unit for flail chest, sternal fracture, pulmonary contusion, pleural or mediastinal lesion not requiring surgery, were included over a twelve month period. A complete cardiac assessment was carried out, including a physical examination, electrocardiogram, chest X-ray, enzyme assay (ALAT, ASAT, LDH, CPK and MB isoenzyme), two-dimensional echocardiography (2D-EC), thallium-201 scintigraphy. Myocardial contusion was diagnosed when an area of decreased or absent thallium-201 uptake was found in the scintigraphy. These latter results were compared with those obtained with the other investigations. Sixteen patients, mean age 34 years, were included; two who died before the end of the investigations were excluded. 2D-EC provided the most useful data (pericardial effusions in a third of the cases). The physical examination, enzyme assays, and chest films were of low value. The investigations carried out six months after the initial trauma showed that long term follow-up was not required. All patients were asymptomatic ten months after their trauma Although the diagnosis of myocardial contusion was made in half the cases using thallium-201 scintigraphy, 2D-EC provided reliable data and had the advantage to be carried out at the patient's bedside.

Adult↗
PubMed2006

Intrathecal bupivacaine protects against extension of lesions in an acute contusive spinal cord injury model.

BACKGROUND AND OBJECTIVE: We recently demonstrated that intrathecal bupivacaine before or after acute photochemical spinal injury improved functional outcome in rats. However, the closest model to spinal trauma is the contusive weight-drop method. The aim of this study was to evaluate functional, electrophysiological and anatomical consequences of a contusive spinal-cord lesion in rats with or without an intrathecal injection of bupivacaine. METHODS: Fifteen minutes before a contusive spinal lesion, 18 rats received intrathecally either 0.5% bupivacaine (Group T) or saline (Group C). During an 18-days period, motor and sensory functions were evaluated, and bladder voiding dysfunction was noted. Somatosensory evoked potential testings were performed at day 18. Then, the intact spinal cord area at the epicentre of the lesion and the extent of the lesion were measured. RESULTS: Motor deficit was less and inclined-plane stability was better in treated animals at all times, the scores were statistically different from day 7. There were no differences concerning the sensory test. Despite no significant difference, there were less spinal bladders in the T group from day 7. Somatosensory evoked potential latencies were longer in T group, but only the first negative component (N1) was statistically significant. Amplitudes were higher in T group, but were not statistically different. The spinal cord intact area at the epicentre of the lesion was higher in the T group (1.23 +/- 0.8 mm(2) vs. 0.81 +/- 0.39 mm(2); P < 0.05). The extent of the lesion was higher in the C group (9.4 +/- 2.9 mm vs. 6.4 +/- 3.4 mm; P < 0.05). CONCLUSION: Intrathecal 0.5% bupivacaine provide a neuroprotective effect by decreasing functional, electrophysiological and anatomical consequences after a contusive spinal cord injury.

Anesthetics, Local↗
PubMed2006

MR imaging of head trauma: visibility of contusions and other intraparenchymal injuries in early and late stage.

The aim of this study was to investigate the visibility of traumatic brain lesions on conventional magnetic resonance images (MRI) in early and late phase. Thirty-six patients were studied 1 week and 1 year after a traumatic brain injury. A similar MRI technique was used in both studies; T2-weighted fast or turbo spin echo images, fluid attenuated inversion recovery (FLAIR) images and T1-weighted images were used for analysis. The number and extent of contusions and semi-quantitative score of other traumatic intraparenchymal lesions were compared in the early and late phase. Contusions were seen in 18 patients both in acute and 1 year MRI; the number and extent of visible contusions was significantly decreased at 1 year. Other traumatic intraparenchymal lesions were detected in 12 patients in early MRI and in 10 patients in late MRI. The number of visible lesions and the semi-quantitative scores were significantly lower at 1 year. There is a significant decrease in the visibility of both cortical contusions and other intraparenchymal injuries in late MRI studies compared with studies in acute stage using conventional imaging techniques. Thus, early phase MRI is essential for the detection of brain injury at least using conventional imaging techniques.

Accidental Falls↗
PubMed2003

Differential concentration-dependent effects of prolonged norepinephrine infusion on intraparenchymal hemorrhage and cortical contusion in brain-injured rats.

Under clinical conditions catecholamines are infused to elevate cerebral perfusion pressure and improve impaired posttraumatic cerebral microcirculation. This, however, is associated with the risk of additional hemorrhage in the acute phase following traumatic brain injury. In the present study we investigated the dose-dependent effects of prolonged norepinephrine infusion on arterial blood pressure, blood glucose, and structural damage in brain-injured rats. At 4 h following induction of a focal cortical contusion (CCI), 40 rats were randomized to receive low (0.15), medium (0.3), or high dose (1 microg/kg/min) norepinephrine. Control rats were given equal volume of NaCl. Norepinephrine and NaCl were infused intravenously via Alzet osmotic pumps for 44 h. Mean arterial blood pressure (MABP), blood gases and blood glucose were determined before, at 4, 24, 48 h after CCI in repeatedly anesthetized rats (n = 28). Systolic arterial blood pressure (SABP) was measured using the tail cuff method in awake, restrained rats (n = 12). Cortical contusion and intraparenchymal hemorrhage volume were quantified at 48 h in all rats. MABP determined in anesthetized rats was only marginally increased. SABP was significantly elevated during infusion of medium and high dose norepinephrine in awake rats, exceeding 140 mm Hg. Medium and high dose norepinephrine significantly increased cortical hemorrhage by 157% and 142%, without increasing the cortical contusion volume. Low dose norepinephrine significantly reduced the cortical contusion by 44%. Norepinephrine aggravates the underlying brain damage during the acute posttraumatic phase. Future studies are needed to determine the least deleterious norepinephrine concentration.

Animals↗
PubMed1993

Unilateral cortical contusion injury in the rat: vascular disruption and temporal development of cortical necrosis.

Cerebrovascular disruption and cortical pathology resulting from either moderate (M-TBI) or severe (S-TBI) traumatic brain injury produced by a pneumatically-driven cortical contusion device were assessed in adult male rats sacrificed at 6 and 24 h or 8 and 30 days after injury to the right sensorimotor cortex. Epidural, subdural, subarachnoid, petechial (cortex and corpus callosum), and/or intraventricular hemorrhage was present in all animals, more extensively and severely following S-TBI. At 6 or 24 h after TBI, acidophilic (acid fuchsin-positive) neurons were numerous and widespread (S-TBI > M-TBI) in the ipsilateral contused cortex. By 8 days few acidophilic neurons were present in peri-impact regions of the ipsilateral neocortex, and none were detected in cortex 30 days postinjury. Both M-TBI and S-TBI groups had enlarged ipsilateral cortical volumes (edema) at 6 and 24 h post-contusion. Eight and 30 days after injury the mean volume of cortical necrosis was significantly larger in S-TBI than in M-TBI rats, and cortical necrosis in both TBI conditions increased between 8 to 30 days postinjury. These results indicate that this pneumatically-driven contusion device produces reliable and consistent primary and secondary cortical histopathology, the extent of which is related to the severity of initial injury.

Animals↗
PubMed2004

Tempol, a nitroxide antioxidant, improves locomotor and histological outcomes after spinal cord contusion in rats.

We have determined whether the nitroxide antioxidant, tempol, can oppose tissue loss and improve recovery of locomotor function following contusion injury of the spinal cord. Contusion injury was produced in rats at the level of T10 with a weight-drop device and locomotor recovery was determined with the 21-point Basso, Beattie and Bresnahan (BBB) scale. Locomotor function recovered progressively during the 6-week postinjury observation period and was significantly greater in tempol-treated (275 mg/kg i.p., 20 min postinjury) compared to vehicle-treated rats (final BBB scores: 9.1 versus 6.4). Similarly enhanced locomotor recovery was observed with doses of tempol in the range of 138-550, but not 69 mg/kg, and with injection at 48 h postinjury indicating a therapeutic time-window of at least several days. The extent of recovery correlated with measurements of sparing of spinal cord white matter in a region several millimeters in length extending rostrally from the contusion epicenter. In contrast, loss of gray matter was unaffected by tempol treatment. Since tempol acts by scavenging reactive oxygen species (ROS) such as superoxide and hydroxyl radicals, the improved locomotor recovery and spared spinal cord tissue following contusion injury provides evidence of a direct role of ROS-mediated neurodegeneration in spinal cord injury.

Animals↗
PubMed2005

Histopathological and behavioral characterization of a novel cervical spinal cord displacement contusion injury in the rat.

Cervical contusive trauma accounts for the majority, of human spinal cord injury (SCI), yet experimental use of cervical contusion injury models has been limited. Considering that (1) the different ways of injuring the spinal cord (compression, contusion, and transection) induce very different processes of tissue damage and (2) the architecture of the spinal cord is not uniform, it is important to use a model that is more clinically applicable to human SCI. Therefore, in the current study we have developed a rat model of contusive, cervical SCI using the Electromagnetic Spinal Cord Injury Device (ESCID) developed at Ohio State University (OSU) to induce injury by spinal cord displacement. We used the device to perform mild, moderate and severe injuries (0.80, 0.95, and 1.1 mm displacements, respectively) with a single, brief displacement of <20 msec upon the exposed dorsal surface of the C5 cervical spinal cord of female (180-200 g) Fischer rats. Characterization of the model involved the analysis of the temporal histopathological progression of the injury over 9 weeks using histochemical stains to analyze white and gray mater integrity and immunohistochemistry to examine cellular changes and physiological responses within the injured spinal cord. Accompanying the histological analysis was a comprehensive determination of the behavioral functionality of the animals using a battery of motor tests. Characterization of this novel model is presented to enable and encourage its future use in the design and experimental testing of therapeutic strategies that may be used for human SCI.

Animals↗
PubMed2001

Procalcitonin versus interleukin-6 levels in bronchoalveolar lavage fluids of trauma victims with severe lung contusion.

OBJECTIVE: To examine whether measurement of procalcitonin (PCT) in comparison with interleukin-6 is a reliable marker to score the extent of lung contusion in bronchoalveolar lavage (BAL) fluids in polytrauma patients. DESIGN: Prospective, nonrandomized, observational study. SETTING: Twelve-bed intensive care unit in a 1,100-bed primary care university hospital. PATIENTS: Fourteen trauma victims presenting with severe lung contusion and acute lung injury or acute respiratory distress syndrome were enrolled in the study. INTERVENTIONS: Bronchoscopy with collection of lavage fluid and serum blood samples. Samples were obtained on days 1 and 2 after severe chest trauma, and lung contusion was assessed by computed tomography scan. MEASUREMENTS AND MAIN RESULTS: PCT was detectable in BAL fluids of all 14 patients. A significant correlation for PCT serum and BAL levels was found on day 2 (p =.0063). For PCT, no significant correlations (Spearman rank) were found to the lung injury score (p =.93), the abbreviated injury scale-lung (p =.33), or the sepsis-related organ failure assessment score-lung (p =.38). Also, for interleukin-6 there was no significant correlation to the lung injury score (p =.62), abbreviated injury scale-lung (p =.45), or the sepsis-related organ failure assessment score-lung (p =.54). CONCLUSIONS: PCT and interleukin-6 BAL levels cannot be considered as reliable parameters to assess the extent of lung contusion.

Adult↗