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Changes in regional cerebral blood flow after hyperventilation in the pig with an induced focal cerebral contusion.

Changes in regional cerebral blood flow in anaesthetized pigs with an induced focal cerebral contusion were studied before and after two grades of hyperventilation. A reduction in arterial tension of CO2 with 0.70 mmHg and a further reduction of 0.55 mmHg did not change the CO2 reactivity. Reactivity in both injured and macroscopically normal regions was the same, revealing an average of 39.3% flow change per kPa change in CO2 tension. Regions with low flow after the contusion had an equally big reduction apparently leading to hypoxia because global metabolic rate was unchanged.

Animals↗

Brain contusion in minor cranial traumas.

Minor cranial traumas without surgical emergency account for about 4% of admissions to our Neurological Service. We consider here 226 consecutive cases. Investigations include: clinical examination, skull X-rays, CSF, EEG, CT, isotopic cisternography. The aim of this study is to define the clinical characteristics of patients with minor head trauma and the priority of instrumental investigations. Correlation between clinical and laboratory findings suggests that: X-ray examination is not predictive of CSF hemorrhage or brain contusion; the CSF is bloody in 1/3 of asymptomatic cases and in 1/6 of cases without fracture; the EEG shows indirect signs of brain contusion even in cases without CT evidence; small subdural hematomas are best diagnosed by CT scan.

Adolescent↗

Evaluation of the apoptosis-related proteins of the BCL-2 family in the traumatic penumbra area of the rat model of cerebral contusion, treated by hyperbaric oxygen therapy: a quantitative immunohistochemical study.

The growth and progression of traumatic brain injury (TBI) lesions depend significantly on developments in the traumatic penumbra area, perilesional region, where delayed neuronal death occurs. Recent data supports the important role of apoptosis in delayed cell death in TBI. Previously we demonstrated a significant reduction of apoptosis in traumatic penumbra in animals treated by hyperbaric oxygen (HBO). In this study we evaluate the expression of apoptosis-related proteins of the Bcl-2 family (Bcl-2, Bax and Bcl-xL) in the traumatic penumbra area in correlation with the extent of apoptosis in the rat model of focal cerebral contusion, treated by HBO. Sprague-Dawley rats underwent cortical dynamic deformation, some with subsequent hypoxemia. A group of both hypoxemic and non-hypoxemic animals was treated by HBO. The pathological study was based on immunohistochemical staining of the brain sections for Bcl-2, Bax and Bcl-xL with quantitative evaluation of staining by image analysis. The expression of Bcl-2 in hypoxemic animals was lower than in non-hypoxemic animals, but a significant increase in Bcl-2 expression was seen in both groups after HBO treatment. Bcl-xL also demonstrated an increase after HBO treatment but less significant. Staining for Bax protein did not demonstrate significant change after treatment. These data correlate well with the reduction of TUNEL-positive cells in traumatic penumbra after HBO treatment. We concluded that the apoptotic mechanisms are important in delayed cell death in TBI and that post-traumatic hypoxemia increases the intensity of apoptosis, probably through a decrease in Bcl-2 and Bcl-xL expression which normally repress apoptosis. The beneficial effect of HBO treatment in our model of brain contusion correlates well with the increased expression of anti-apoptotic proteins (Bcl-2 and Bcl-xL) following treatment and the appropriate decrease in the extent of apoptosis. In light of these results, the usage of HBO is justified as neuroprotective treatment in TBI.

Animals↗

Up-regulation of intercellular adhesion molecule 1 in cerebral microvessels after cortical contusion trauma in a rat model.

A study was made on the expression of the intercellular adhesion molecule 1 (ICAM-1) in cerebral microvessels after cortical contusion trauma of the rat brain. The trauma was produced by a free-falling weight on the exposed dura of one fronto-parietal lobe. Immunohistochemistry was done on cryostat sections using a monoclonal antibody and the reaction product was visualized using the avidin-biotin-peroxidase complex method. Control and sham-operated rats showed immunostaining of some penetrating arteries of the cerebral cortex, the epithelial cells of the choroid plexus and occasional microvessels of the brain parenchyma. The same pattern of immunostaining was seen in rats that were subjected to trauma and killed after 30 min. All rats with contusion trauma that were allowed to survive for 6-72 h showed a substantial increase in the number of immunostained capillaries throughout the site of the lesion. The ipsilateral hippocampus showed a mild to moderate increase in the number of immunostained microvascular profiles. This phenomenon was also present in the lateral thalamus of some rats. The staining was seen as an uninterrupted line at the position of the endothelial cells, indicating an upregulation of this adhesion molecule after brain trauma. Up-regulation of ICAM-1 is a well-known phenomenon in inflammatory and ischemic lesions of the brain but has not previously been described in detail in traumatic brain injury. ICAM-1 may be involved in the production of several post-traumatic events such as leukocyte adhesion, microcirculatory disturbances and edema formation.

Animals↗

Retinal vascular occlusion following ocular contusion.

PURPOSE: To describe an unusual fundus abnormality in eyes after trauma and its pathophysiologic basis. METHODS: Prospective, observational case series of five consecutive male patients who suffered retinal vascular occlusions after ocular contusion. RESULTS: We present five cases of retinal vascular occlusions following ocular contusion, found on routine fluorescein angiography in otherwise healthy individuals. CONCLUSIONS: Different patterns of retinal vascular occlusions can occur in ocular trauma. The pathogenesis of these occlusions may be related to direct damage to the endothelium.

Adolescent↗

Acute alterations of glutamate, glutamine, GABA, and other amino acids after spinal cord contusion in rats.

Spinal cord injury (SCI) leads to an alteration of energetic metabolism. As a consequence, glutamate, glutamine, aspartate and other important amino acids are altered after damage, leading to important disregulation of the neurochemical pathways. In the present study, we characterized the acute-phase changes in tissue concentration of amino acids involved in neurotransmitter and non-neurotransmitter actions after SCI by contusion in rats. Animals were submitted to either laminectomy or SCI by contusion and sacrificed at 2, 4, 8, and 12 h after lesion, for the analysis of tissue amino acids by HPLC. Results showed that both aspartate and glutamate contents diminished after SCI, while glutamine concentrations raised, however, the sum of molar concentrations of glutamate plus glutamine remained unchanged at all time points. GABA concentrations increased versus control group, while glycine remained unchanged. Finally, citrulline levels increased by effect of SCI, while taurine-increased only 4 h after lesion. Results indicate complex acute-phase changes in amino acids concentrations after SCI, reflecting the different damaging processes unchained after lesion.

Animals↗

A rational screening and treatment strategy based on the electrocardiogram alone for suspected cardiac contusion.

The charts of 71 patients admitted to one teaching institution over a 4-year period with a primary or secondary diagnosis of "rule out cardiac contusion" and of another 62 admitted to a second institution with more severe injuries and suspicion of cardiac contusion were reviewed to determine if mortality or morbidity would have occurred if all patients with normal electrocardiograms (EKGs) in the emergency department (ED) were discharged (or admitted to unmonitored beds for other injuries). Only 13 patients developed cardiac problems: two elderly patients died in the ED, while the others experienced arrhythmias or, less commonly, pump failure requiring treatment or observation. All 13 had EKG changes present while still undergoing evaluation in the ED: 11 had a specific problem on arrival, 1 developed a problem while still being evaluated in the ED, and the 13th had what was probably an iatrogenic problem. Importantly, 5 of 12 patients had normal creatine phosphokinase-MB fractions, and 5 of 9 had normal echocardiograms. No patient with a normal EKG had subsequent cardiac problems. Operative intervention for other injuries was necessary in 26 patients overall, and there was no cardiac morbidity. We conclude that had the EKG been used as the sole screening tool, approximately 25% of these patients could have been discharged from the ED without missing problems. In addition, management would have been greatly simplified, and the hospital would have realized substantial savings, both in terms of direct costs and in the freeing of valuable and scarce resources.

Adult↗

Elevation and clearance of extracellular K+ following contusion of the rat spinal cord.

The elevation and clearance of extracellular potassium following a standard contusion injury was studied in the thoracic spinal cord of rats. Animals were anesthetized, paralyzed, laminectomized at T9-T11, then artificially ventilated. A 10-g rod was released 5.0 cm above the cord with the dura intact. After impact, the dura-arachnoid and pial membranes were incised to allow penetration of K(+)-selective microelectrodes. Electrodes utilized a valinomycin ionophore and were double-barreled, with tip diameters of 3-5 microns. Extracellular potassium activity ([K+]o) increased with the depth of penetration. The maximum values of [K+]o occurred at depths greater than 500 microns, and remained so with time after injury. These data indicate that a dorsal-ventral gradient of [K+]o develops in spinal cords contused from the dorsal surface, with the greatest elevation of [K+]o in the gray matter. In 8 preparations, the maximum [K+]o was 65 +/- 8 mM (mean +/- S.E.M.) at 5 +/- 1 min after injury. The [K+]o peak values decayed with a half-time of 11.0 +/- 3.4 min. Compared with data available for the injured cat spinal cord, the peak [K+]o recovered relatively rapidly. Although a simple diffusion model could account for the rapid clearance of [K+]o, the persistence of dorsal-ventral [K+]o gradients could not be explained by such a model. It is postulated that secondary injury processes contributed to the persistent [K+]o gradients.

Animals↗

Lateralized effect of unilateral somatosensory cortex contusion on behavior and cortical reorganization.

Previous studies have shown that rats recover function after unilateral somatosensory cortex lesions, possibly by transfer of information processing to other brain areas not normally involved in those functions. In the present study, adult rats underwent unilateral contusions of the somatosensory cortex with ablation of the barrel receptor field. Behavioral testing with modified beam-walking and sensory neglect tasks demonstrated persistent somatosensory deficits in rats with left contusions but no apparent deficits in right injured animals. After 2 months, the [14C]2-deoxyglucose (2-DG) method was used to show the metabolic activity produced by unilateral stimulation of the facial vibrissae. In left injured animals, cortical metabolic activity rostral and caudal to the injury site was depressed both under basal conditions and during right vibrissal stimulation. On the other hand, comparison of the pattern of [14C]2-DG uptake in the intact, right cortex revealed changes in the pattern of glucose utilization associated with left injury combined with right vibrissal stimulation. Pattern changes were quantified by measuring the area in which glucose utilization was within the highest 25% of this range (high activity area; HAA). Right vibrissal stimulation in left injured rats caused an expansion of this HAA in the intact occipital/temporal cortex. Also, in the intact somatosensory cortex of left injured rats, there was an enlarged HAA whether or not vibrissal stimulation was performed. Thus, a combination of depressed peri-injury metabolic activity and aberrant activity in remote brain areas occurs following unilateral somatosensory cortex injury. It remains to be shown whether these factors ameliorate or contribute to persistent behavioral deficits.

Animals↗

A controlled pneumatic technique for experimental spinal cord contusion.

The 'Allen technique', a weight-drop procedure introduced in 1911, remains the most widely used technique for experimental spinal cord contusion. Control of injury severity in this procedure is achieved by alteration of the height from which the standardized weight (usually 20 g) is dropped. It has not been possible in this technique to independently vary the amount of cord compression and the initial velocity of compression, since both are related to drop-weight kinetic energy. Our approach uses a constrained stroke pneumatic impactor to afford independent control of these two parameters. Mechanical testing of the device has verified the accuracy and repeatability of impact velocity and cord compression. More importantly, a pilot series at 2 m/s contact velocity with a range of compression has demonstrated neurophysiologically distinct levels of spinal cord injury as a function of compression. This includes a 'moderate' functional injury with impaired and delayed neuronal conduction through the injury site. Such a 'moderate' injury, at the threshold between recovery and permanent cord dysfunction, is particularly promising for the study of mechanisms underlying progressive post-contusion pathology; 'moderate' injury has not been reproducibly generated in weight-drop techniques.

Animals↗

The intra-aortic balloon pump as an adjunctive therapy for severe myocardial contusion.

The management of patients with post-traumatic myocardial contusion requires close electrocardiographic and hemodynamic monitoring. When complications such as cardiogenic shock occur, aggressive treatment using Swan-Ganz catheterization for monitoring of intravascular volume and cardiac inotropic support are necessary. Failure to restore hemodynamic stability using these measures is an indication for the use of intra-aortic balloon pump counterpulsation. A case of successful management of a patient with post-traumatic myocardial contusion complicated by refractory cardiogenic shock using intra-aortic balloon pump counterpulsation is presented. Use of the intra-aortic balloon pump improved cardiac output, eventually resulting in hemodynamic stabilization.

Adult↗

Excoriations and contusions of the skin as artefacts in fictitious sexual offences.

Some women reporting a sexual offence to the police inflict injuries on themselves, usually with the help of pointed and/or cutting tools, in order to make fictitious assaults more credible. If there is a classical pattern of the findings, such fictitious assaults are easier to identify. However, it is more difficult to distinguish genuine from fictitious injuries, if blunt force is used. This paper reports on 4 such cases, and the characteristics of self-inflicted excoriations and skin contusions are discussed. In the cases described, the excoriations were produced by scratching with the person's own fingernails or by rubbing the skin against a rough surface; contusion bleeding was caused by pinching (lifting and compressing skin folds with the fingers). The pattern of the injuries showed striking parallels to classical patterns: multiple lesions in grouped, parallel and symmetrical arrangement and of evenly minor intensity; preference of body regions within easy reach; no damage of the clothing, or if any, damage inconsistent with the injuries as described.

Journal Article↗

Combining motor training with transplantation of rat bone marrow stromal cells does not improve repair or recovery in rats with thoracic contusion injuries.

Previous studies have demonstrated that either transplantation of bone marrow stromal cells (MSC) or physical exercise regimens can elicit limited functional recovery following spinal cord injury, presumably through different mechanisms. The present study examined whether transplantation of MSC derived from transgenic Fischer alkaline phosphatase (AP) rats, in combination with exercise, would have synergistic effects leading to recovery of function that is greater than either alone. Adult female Sprague-Dawley rats received a moderate thoracic contusion injury and were divided into three groups: operated controls (Op-Control), MSC transplant recipients (MSC), and MSC transplant recipients plus exercise (MSC+Ex). Nine days after contusion, a Vitrogen matrix +/-one million MSC was injected into the lesion site in all animals. Immunosuppression with high doses of Cyclosporine A, required for MSC survival, was provided for all animals. Passive hindlimb exercise on motorized bicycles was applied 1 h/day, 3 days/week to the MSC+Ex group. A battery of behavioral tests was performed weekly to assess motor and sensory functions in all 3 groups for 12 weeks. Morphological evaluation included MSC survival, evidence of axonal growth into grafts, phenotypic analysis of MSC, and lesion/transplant size. The weight of the medial gastrocnemius muscle, a hindlimb muscle activated during stance, was used to identify extent of atrophy. No differences in motor recovery were found among the three groups. MSC survived 3 months after transplantation, indicating that the immunosuppression treatment was successful. The extent of survival was variable, and there was no correlation between MSC survival and behavioral scores. The matrix persisted, filling the lesion cavity, and some axons grew into the lesion/matrix but to a similar extent in all groups. There was no difference in lesion/matrix size among groups, indicating no neuroprotective effect on the host provided by the treatments. Immunocytochemical analysis provided no evidence that MSC differentiated into neurons, astrocytes or oligodendrocytes. Muscle mass of the medial gastrocnemius was diminished in the Op-Control group indicating significant atrophy, but was partially preserved in both the MSC and MSC+Ex groups. Our results indicate that combining the beneficial effects of rat MSC and this exercise protocol was not sufficient to enhance behavioral recovery.

Animals↗

A neuroprotective role of glial cell line-derived neurotrophic factor following moderate spinal cord contusion injury.

The present study investigated neuroprotective effects of glial cell line-derived neurotrophic factor (GDNF), a distant member of the transforming growth factor-beta (TGF-beta) superfamily, following moderate contusive spinal cord injury (SCI) in adult rats. A T11 spinal cord contusion injury was made using an Infinite Horizon impactor (IH; impact force=150 kDyn) and recombinant human GDNF at two concentrations (rhGDNF; 1 or 5 microg/microl), or saline vehicle was delivered intrathecally for 28 days using an Alzet miniosmotic pump. We demonstrated that, at 7 weeks postinjury, GDNF infusion significantly reduced the total lesion volume by 34-42% (assessed stereologically) and increased the percentage of white matter sparing by 10-13% (measured at the injury epicenter), as compared to the vehicle infusion. Retrograde tracing revealed that GDNF infusion resulted in a significant increase in the number of FluoroGold (FG)-labeled neurons in propriospinal regions as well as in two supraspinal regions, that is, the medullary and pontine reticular formation, and the lateral vestibular nucleus. Immunofluorescent staining confirmed that the spared white matter contained neurofilament-positive axons. However, transcranial magnetic motor-evoked potential (tcMMEP) assessment revealed no significant difference in onset latency and amplitude between the GDNF- and vehicle-infused groups. These results suggest that GDNF has a strong neuroprotective effect on white matter sparing and the sparing of a subset of proprio- and supraspinal axons following injury. However, a return of tcMMEPs requires the sparing and/or myelination of axons in a defined region of the white matter which was either not spared or remyelinated at this level of injury severity.

Animals↗

Spatial and temporal gene expression profiling of the contused rat spinal cord.

Microarray technology was used to examine gene expression changes following contusive injury of the adult rat spinal cord. To obtain a global understanding of the changes triggered by the injury, differential gene expression was examined spatially, using tissue samples from the epicenter of injury as well as 1 cm rostral and 1 cm caudal to the epicenter, and temporally, at 3 h, 24 h, 7 days, and 35 days post-injury. To filter out gene expression changes that were due to the laminectomy, samples of contused tissue were compared to laminectomy-only controls. We took advantage of four different, complementary methods of data analysis to detect differentially expressed genes. We have identified functional groups of genes that are differentially regulated in our model, including those associated with apoptosis, cell cycle, inflammation, and cholesterol metabolism. Our analysis has led to the identification of novel potential therapeutic targets within each group of genes that is discussed.

Animals↗

Serotonergic fiber sprouting to external anal sphincter motoneurons after spinal cord contusion.

The present study analyzed the anatomical plasticity of serotonergic immunoreactive projections to external anal sphincter (EAS) motoneurons, and the behavioral plasticity of EAS reflexes, penile erection, and locomotion in rats with spinal contusion injury (SCI) or complete spinal cord transection (TX). Electromyographic activity of the EAS, penile erection latency, and BBB locomotor score exhibited parallel recovery over the 6-week recovery period after contusion SCI. This pattern of recovery was not observed in TX animals. While locomotor scores demonstrated a small increase after TX, erectile and anorectal function remained at abnormal levels established immediately after injury. Serotonergic immunofluorescent (5-HT-IF) staining at the lesion site identified a small number of fibers spared after SCI that may provide a substrate for functional recovery. Pixel density measurements of 5-HT-IF in the vicinity of retrogradely labeled EAS and unlabeled pudendal motoneurons necessary for penile erection provide indirect evidence of serotonergic sprouting that parallels the observed functional recovery in animals with SCI. No 5-HT-IF was detected caudal to the injury site in TX animals. These studies indicate: (1) lumbosacral eliminative and reproductive reflexes provide a valid means of studying the mechanisms of post-SCI plasticity; (2) the similar recovery curves suggest similar return of descending control, perhaps through sprouting of descending serotonergic fibers; (3) the observed deficits after TX likely represent the permanent removal of descending inhibition and reflect reorganization of segmental circuitry.

Anal Canal↗

Tissue displacement and impact force are important contributors to outcome after spinal cord contusion injury.

Spinal cord contusion injury in rodents is widely used as a model for spinal cord trauma in humans. Several biomechanical variables can influence injury outcome. In this work, we have assessed the influence of impact force and displacement of the spinal cord at the time of contusion injury on the severity of locomotor deficits and histopathological changes. Our work indicates that there is a linear relationship between force and tissue displacement, and that both these factors contribute to injury outcome. Furthermore, our work also suggests that setting narrow limits for the actual force applied (+/-5 kdyn) and tissue displacement (within a 200 microm range) will yield more consistent outcomes and provide greater sensitivity in detecting changes, regardless of the type of impactor device used.

Animals↗

Transplantation of Schwann cells to subarachnoid space induces repair in contused rat spinal cord.

Schwann cell transplantation is well known to induce repair in the injured spinal cord which disables millions of injured patients throughout the world. An ideal route of delivering the grafted Schwann cells to the spinal cord should neither cause more injury nor reinitiate inflammatory events and also provide a favorable milieu to the grafted cells. In this study, we have utilized subarachnoid route to transplant Schwann cells and evaluated their effects in a contusive model of spinal cord injury. Adult rats weighing 100-140 g were experimentally injured by crushing the spinal cord with a titanium clip and then divided into four groups (Tracing, Control, Medium-treated and Schwann cell-treated). Cultured Schwann cells (5x10(4) cells in 5 microl) or medium were injected to the animals of corresponding groups via subarachnoid space at the injured site 7 days after injury. In tracing group, Schwann cells (labeled with Hoechst) demonstrated their presence within spinal cord 7 days after transplantation. Evaluation of locomotor performance of animals for 60 days after injury showed that animals treated with Schwann cells had significant improvement (P<0.01). Similarly, the axon density at the site of injury was significantly higher. The results indicate the efficacy of subarachnoid route for the transplantation of Schwann cells in inducing repair of the contused spinal cord. We conclude that this route can be useful for the transplantation of Schwann cells and offers a hope for the patients suffering from spinal cord injury.

Animals↗