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Background: Complex procedures in knee surgery, such as anterior cruciate ligament (ACL) reconstruction with the double bundle technique are not specially recognized within the German diagnosis-related groups (G-DRG) system. Hence, the goal of the present study was to perform a cost unit calculation and evaluate how ACL reconstruction in single versus double bundle techniques is remunerated., Patients and Methods: In 30 patients ACL reconstruction was performed with the single bundle technique (group A) and in 21 an anatomic double bundle reconstruction (group B) was performed. All costs including those for human resources, implants and materials, as well as general costs for administration and facilities were calculated., Results: All cases entered one DRG category, the I30Z "complex procedures at the knee joint". Thus, the revenue in 2008 was 2,996.65 euro per case and in 2009 3,120.35 euro per case. Calculating all costs, the profit contributions in 2008 and 2009 were 592,42 euro and 716,12 euro, respectively for group A. However, in group B the profit contributions were 314,68 euro and 438,38 euro, respectively., Conclusion: Performing the double bundle technique for ACL reconstruction in a university hospital setting, significant cost reductions are needed to achieve the revenue generated by the single bundle technique. Additional changes of the relative weighting in the DRG are also necessary.

Background: The incidence of pulmonary failure in trauma patients is considered to be influenced by several factors such as liver injury. We intended to assess the association of various potential predictors of pulmonary failure following thoracic trauma and liver injury., Methods: Records of 12,585 trauma patients documented in the TraumaRegister DGU® of the German Trauma Society were analyzed regarding the potential impact of concomitant liver injury on the incidence of pulmonary failure using uni- and multivariate analyses. Pulmonary failure was defined as pulmonary failure of ≥ 3 SOFA-score points for at least two days. Patients were subdivided according to their injury pattern into four groups: group 1: AIS thorax < 3; AIS liver < 3; group 2: AIS thorax ≥ 3; AIS liver < 3; group 3: AIS thorax < 3; AIS liver ≥ 3 and group 4: AIS thorax ≥ 3; AIS liver ≥ 3., Results: Overall, 2643 (21%) developed pulmonary failure, 12% (n= 642) in group 1, 26% (n= 697) in group 2, 16% (n= 30) in group 3, and 36% (n= 188) in group 4. Factors independently associated with pulmonary failure included relevant lung injury, pre-existing medical conditions (PMC), sex, transfusion of more than 10 units of packed red blood cells (PRBC), Glasgow Coma Scale (GCS) ≤ 8, and the ISS. However, liver injury was not associated with an increased risk of pulmonary failure following severe trauma in our setting., Conclusions: Specific factors, but not liver injury, were associated with an increased risk of pulmonary failure following trauma. Trauma surgeons should be aware of these factors for optimized intensive care treatment.

Object: This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting., Methods: Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Sham-injured mice of both genotypes were used as controls (9 in each group). The mice were subjected to neurobehavoral tests evaluating learning/acquisition (Morris water maze) and motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume, as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal staining with doublecortin antibody was used to evaluate neurogenesis after the insult., Results: Brain-injured XPA(-/-) mice exhibited delayed recovery from impairment in neurological motor function, as well as pronounced cognitive dysfunction in a spatial learning task (Morris water maze), compared with injured XPA(+/+) mice (p < 0.05). No differences in cortical lesion volume, hippocampal damage, or thalamic cell loss were detected between XPA(+/+) and XPA(-/-) mice after brain injury. Also, no difference in the number of cells stained with doublecortin in the hippocampus was detected., Conclusions: The authors' results suggest that lack of the DNA repair factor XPA may delay neurobehavioral recovery after TBI, although they do not support the notion that this DNA repair deficiency results in increased cell or tissue death in the posttraumatic brain.

Introduction: The rate of periprosthetic femoral fractures after hip arthroplasty is rising and the estimated current lifetime incidence is 0.4-2.1%. While most authors recommend revision arthroplasty in patients with loose femoral shaft components, treatment options for patients with stable stem are not fully elucidated., Method: Against this background we performed a retrospective chart analysis with clinical follow-up examination of 32 cases that sustained a Vancouver type B1 or C periprosthetic fracture (stable stem)., Patients: Overall 16 cases were treated by open reduction and internal fixation (ORIF) by plate osteosynthesis and 16 cases by revision arthroplasty (RA). Both groups were comparable regarding age, gender, follow-up time interval, time interval from primary hip arthroplasty to fracture and rate of cemented femoral components, but more type C fractures were treated by ORIF., Results: Functional outcome expressed by the median timed "Up and Go" test did not differ significantly (30 s ORIF vs. 24 s RA, P = 0.19). However, by comparable systemic complications surgery-related complications were significantly more frequent in plate osteosynthesis (ORIF n = 10 vs. RA n = 3, P = 0.03). Based on our results, further studies, preferable via a multicenter approach, should focus on identifying patients that benefit from ORIF in periprosthetic fractures. A misinterpretation of type B2 fractures with loose implant as type B1 fractures may cause implant failure in case of ORIF., Conclusion: The use of angular stable implants, additional cable wires or bone enhancing means is recommended.

Background: Although the incidence of pediatric patients in emergency services is as low as 5-10%, trauma remains one of the leading causes of death during childhood. Only a few reports exist about the quality of the initial treatment of pediatric trauma patients. Therefore, we tested the hypothesis of whether prehospital treatment and emergency management in pediatric trauma patients is similar to the treatment that is provided for adult patients., Materials and Methods: We performed a retrospective data analysis of the German Trauma Registry of the DGU from January 1993 to December 2007. Exclusion criteria were missing information about injury severity and/or age and patients older than 50 years. All pediatric patients were subdivided into five groups (infants 0-1 year, toddlers 2-5 years, children 6-9 years, pupils 10-13 years, teenagers 14-17 years) with regard to their age and were compared with the adult cohort (18-50 years). From 24,396 patients, 2,961 were below 18 years of age, thus, about 12% of the whole population of injured patients below the age of 50 years., Results: 66.4% of infants sustained relevant head injuries (Abbreviated Injury Scale [AIS] ≥3), and this rate declined with increasing age. The mean Injury Severity Score (ISS) increased from 21.0 (±11.6) in the group of infants to 26.7 (±13.9) in the adult cohort. In all groups, the majority of patients were male. The injury pattern differed according to age, with predominant traumatic brain injury (TBI) in infants. During the preclinical treatment, infants were less often intubated and this was contrasted by a higher rate of cardiopulmonary resuscitation in this group (infants 16.2%, toddlers 6.8%, adults 3.1%). Diagnostic multislice computed tomography (CT) examination was less often performed in infants as compared to the other groups (infants 57.1%, toddlers 77.2%, adults 77.8%). Mortality and quality indicators such as timelines show no significant differences between children and adults., Conclusion: We observed typical age-dependent differences regarding the injury pattern and severity and differences referring to the preclinical and initial treatment. With respect to the high rate of serious TBI in the infants and toddlers age groups, a more focused education and training of emergency physicians and paramedics should be considered.

Background: The prognosis of severely injured patients depends on a rapid diagnosis and early initiation of therapeutic procedures., Material and Methods: To that end a total of 6,927 prospectively documented severely injured patients with an Injury Severity Score (ISS) > or =16 from the Trauma Registry of the German Trauma Society (DGU, 2002-2007) were analyzed with respect to time intervals during emergency trauma treatment., Results: In cases of indicated emergency surgery the average +/-time in the emergency department was 42+/-34 min, in cases of early surgery 75+/-41 min and in cases of transfer to the intensive care unit (ICU) 83+/-43 min, respectively. The time from the last diagnostic procedure until the end of emergency treatment was 12 min (emergency surgery), 26 min (early surgery) and 32 min (ICU), respectively. Level I (78 min) and level II (72 min) trauma centres showed similar mean times in the emergency department while level III trauma centres had a mean time of 86 min. According to this analysis no general correlation between shorter duration of emergency trauma care and reduced mortality could be observed., Conclusion: The duration of time intervals depends on injury severity, treatment after completion of emergency trauma care and the level of the trauma centre. Time management in emergency trauma care can potentially be optimized after completion of the last diagnostic procedure in the emergency room.

Background: Currently, little information is available on functional outcome of periprosthetic humeral fractures after shoulder arthroplasty. This investigation aimed to evaluate functional and radiological outcome and patients' satisfaction following this type of injury treated by open reduction and internal fixation., Methods: Retrospective chart analysis of patients treated at two level-I trauma centers. Patients were examined clinically and radiologically. Additionally, functional outcome was assessed using the established DASH-questionnaire and standardized examination for calculation of the Constant score., Results: Five out of six patients showed complete fracture consolidation with satisfying functional results (mean follow up time 62 weeks). One patient showed major complications with poor outcome. DASH and Constant scores were comparable to those described after primary shoulder arthroplasty., Conclusions: Periprosthetic humeral fractures after shoulder arthroplasty can be treated by angular stable plating with low complication rates and acceptable results.

The increasing average age in the industrialized nations is leading to an increasing number of elderly traumatized patients. Against this background, an analysis of the age-specific characteristics of geriatric traumatized patients is necessary. In this study, 14,869 patients > or = 18 years were analysed, who were prospectively documented in the registry of the German Trauma Society (DGU) between 1996 and 2005. Patients between 18 and 59 years were defined as the control group; their proportion declined from 81.1% in 1996-2000 to 75.4% in 2001-2005. The average age rose from 41.0 years (1996) to 45.3 years (2005). With increasing age a significant increase in severe head injuries of up to 58.9% (> or = 80 years) could be observed. Older patients stayed for a significantly shorter time in hospital and on the ICU. With a comparable injury severity, the lethality after trauma increased with age (18-59 years 13.8%, 60-69 years 24.1%, 70-79 years 35.5%, > or = 80 years 43.6%). The multiply traumatized geriatric patient is different from the normal group in regard to type of injury, therapy and outcome and should therefore be treated taking this fact into consideration.

Although multiple organ failure (MOF) remains the leading cause of death after trauma, the pathogenic cellular and molecular mechanisms underlying MOF are poorly understood. In addition to proinflammatory and anti-inflammatory mediator cascades, the temporal onset of MOF has generated recent interest because the organ systems involved into MOF seem to deteriorate in a time-dependent fashion after trauma. We therefore investigated the temporal course of MOF in traumatized human patients and evaluated and compared the distribution patterns of cytokine expression, including interleukin (IL) 6, IL-8, IL-10, and the soluble tumor necrosis factor-[alpha] receptors sTNF-R p55 and sTNF-R p75 in early-onset versus late-onset MOF. In addition, we analyzed the predictive value of cytokine biomarkers of MOF and lethal outcome. In a prospective observational cohort study conducted at three trauma centers, all patients (n = 352) admitted to two level 1 trauma centers in Germany were enrolled in the study based on the following inclusion criteria: severe traumatic brain injury (TBI) with a Glasgow Coma Scale (GCS) score of 8 or lower and/or distinct changes in cranial computed tomography and/or multiple injuries (MT) to the body (at least two regions had Abbreviated Injury Scale score of 3 or higher). The incidence of MOF was evaluated using the modified Goris-MOF score. The temporal onset of MOF was divided into early-onset MOF (EMOF, developing on days 0-3), late-onset MOF (LMOF, developing on days 4-10), combined early-onset and late-onset MOF (CMOF), and patients never showing signs of MOF during the observation period. In addition, the levels of the serum cytokine markers IL-6, IL-8, IL-10, sTNF-R p55, and sTNF-R p75 were analyzed at specific posttraumatic time points using established enzyme-linked immunosorbent assay techniques. A total of 352 patients (274 men and 78 women; TBI, 101; TBI + MT, 125; MT, 126) were enrolled into the study. Patients assigned to the EMOF group showed specific disruption of pulmonary and cardiocirculatory function, whereas LMOF was significantly associated with hepatic failure. The patients without signs of MOF and the EMOF patients had the same risk of lethal outcome (8.2% vs. 7.5%); LMOF and CMOF were found to be associated with a 3- to 4-fold increase in mortality (38.5% vs. 30.6%, respectively). Analysis of cytokine serum biomarkers revealed that patients with LMOF showed a biphasic elevation of IL-6 and significantly higher sTNF-R concentrations than did all other subgroups (P < 0.001). In addition, the initial values (days 0-1) of sTNF-R p55 and sTNF-R p75 expression levels had a good predictive capacity for the development of LMOF (p55, 0.75; p75, 0.72); values greater than 0.65 were accepted to have a predictive capacity. These results demonstrate that mortality differs significantly between the development of EMOF and LMOF after traumatic injury. Our results also suggest that serum cytokine measurements may be important early biochemical markers for predicting the development of delayed MOF.

Severe traumatic brain injury (TBI) is characterized by a high mortality and poor outcome. The pathomechanisms involved are cytokine-mediated proinflammatory and anti-inflammatory reactions and significant cerebral microcirculatory disorders. The role of endothelin 1 (ET-1), a very potent vasoconstrictive peptide, in the deterioration of cerebral perfusion after trauma is still unclear. The presented study investigated the changes in ET-1 in the cerebrospinal fluid (CSF) and plasma after TBI in humans, with special regard to the presence of subarachnoid hemorrhage (SAH) and clinical outcome. Twenty patients with TBI were consecutively enrolled into the study, 10 patients without SAH (TBI group) and 10 patients with SAH (TBI-H group). Paired samples of plasma and CSF were collected for 10 days after trauma. Analysis of the ET-1 concentrations showed that TBI is associated with initially increased ET-1 values in plasma (TBI, day 1; TBI-H, days 2-3) and significantly increased (P < 0.05, vs. control) CSF concentrations (TBI, days 1-2; TBI-H, days 1-3) in the first days after trauma. In the further time course, ET-1 values declined in both groups, reaching reference values in plasma. The CSF values remained significantly (P < 0.05 vs. control) elevated. Both groups showed a second peak on the beginning of the second week after trauma in plasma and CSF. Whereas plasma concentrations failed to reach significance, CSF values showed a significant peak on day 7 in both groups. The TBI-H patients had significantly (P < 0.05) higher values in the secondary peak compared with patients of the TBI group. The kinetics of traumatic SAH-dependent ET-1 needs to be assessed in further investigations.

In the present investigation we examined regional ATP, glucose, and lactate content in the cortical and subcortical region, in a mouse model of controlled cortcal impact (CCI) injury. In serial tissue sections, bioluminescence imaging of ATP, glucose, and lactate was performed 1 h after a single CCI injury or sham surgery and 15 min, 1, 24, and 48 h after the induction of a second CCI injury 24 h later or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry at the lesion site, at the contralateral site, and in a subcortical region. After repetitive CCI injury, the cortical ATP content decreased bilaterally at 15 min and 1 h, and reached a significant minimum at 24 h, as compared with sham. At 48 h the ATP content bilaterally reached base level again. No significant changes in ATP were found in the subcortical region. After repetitive CCI injury, the lactate content increased bilaterally, reached a significant level at 15 min at the trauma site, and bilaterally reached a significant maximum at 1 h. Thereafter, lactate content decreased below base level without reaching significance and reached baseline again at 48 h. In the ipsilateral subcortical region, lactate content increased transiently above the baseline at 1 h and decreased to a significant minimum at 24 and 48 h. No significant changes were found in the contralateral subcortical area. No significant differences between glucose content in sham animals and the cortical and subcortical area could be measured over time; the subcortical glucose content was bilaterally lower than cortical content at all time points and reached a significant minimum bilaterally at 48 h after repetitive CCI injury compared with cortical glucose content. Single CCI injury did not affect ATP, glucose, and lactate contents at any time point. Repetitive CCI injury caused a more severe depression in cerebral metabolism at early time points after trauma compared with a single CCI injury and indicates that lactate might be an early indicator of post-traumatic metabolic disruption.

Recent studies have reported a significant inflammatory reaction in the brain and the systemic circulation after traumatic brain injury (TBI). Although there is growing knowledge and understanding of the mechanisms and mediators involved in the proinflammatory reaction, little is known about the anti-inflammatory mediators in the brain. As tumor necrosis factor alpha (TNF-alpha) plays a detrimental role in the initiation and promotion of the proinflammatory reactions after TBI, the endogenous scavenger system, represented by the soluble TNF receptors (sTNFRs) p55 and p75, seems to have an important anti-inflammatory capacity by binding to circulating TNF-alpha. To evaluate this potentially anti-inflammatory response to trauma, we analyzed sTNFR p55 and p75 in paired plasma/cerebrospinal fluid (CSF) samples of 29 patients who encountered TBI. Values were compared with reference values obtained from healthy volunteers (n = 91). Patients with TBI showed significantly (P < 0.001) elevated sTNFR p55 and p75 values starting from day 2 and lasting until day 10 if compared with reference values. In contrast to the early increased plasma values p55 and p75 showed slowly increasing CSF values starting on day 4 and 3, respectively. Significantly (P < 0.001) increased CSF values of p 55 were determined on days 4 to 6 and day 9. p75 showed significantly (P < 0.001) elevated values if compared with control values on days 7 and 9. The sTNFR p55 and p75 show a distinct and long-lasting elevation in plasma of patients after TBI. In contrast, CSF values display a delayed and less intense elevation of both receptors in patients with TBI. These findings are suggestive of an imbalance of the proinflammatory and anti-inflammatory reactions of the central nervous system after trauma, with an emphasis on the proinflammatory mechanisms and a slow increase of potentially anti-inflammatory mediators such as the soluble TNFRs after TBI.

We report a retrosternally displaced epiphysiolysis in a 12-year-old child and discuss options for the most appropriate diagnostic and therapeutic approach. If a standard anteroposterior view of the shoulder girdle shows abnormalities or if appropriate clinical suspicion is present, we strongly favor an magnetic resonance imaging study for further workup instead of a computed tomographic scan, which is currently the diagnostic method of choice in clinical algorithms. Radiation exposure is thereby limited and maximum information about possible mediastinal soft tissue complications is obtained using a single diagnostic tool. If open reduction is indicated, retention of the joint or approximation of physeal fracture or treatment of ligamentous injury should be performed without metal devices. These suggestions for future management of these patients should further reduce the use of x-rays in children. In addition, applying a suture instead of using metal for stabilization can avoid the extensively described complications in literature that can potentially result from metal devices. In addition, sutures circumvent the need for a second operation for metal removal.

Numerous recent studies have reported a significant inflammatory reaction in the brain and the systemic circulation following traumatic brain injury (TBI), infection, or neoplasm of the brain with a sequential release of pro- and anti-inflammatory mediators. Although there is growing knowledge and understanding of the mechanisms leading to the often poor outcome of these patients, only a limited database exists on the physiological expression of pro- and anti-inflammatory cytokines and molecules in plasma and particularly in cerebrospinal fluid (CSF). Therefore, we analyzed paired plasma/CSF samples of healthy human volunteers for the physiological concentrations of Interleukin (IL)-6, IL-8, IL-10, soluble TNF-receptors (sTNF-R) p55 and p75, soluble ICAM (sICAM), and soluble E-selectin (sE-selectin). A physiological release of IL-6, IL-8, IL-10, and sTNF-R p55 and p75 was detected in plasma and CSF. In contrast, sICAM and sE-selectin were only detectable in plasma. Pro- and anti-inflammatory mediators exhibited different concentration patterns in plasma and CSF, suggesting a pro-inflammatory predisposition in the central nervous system.

Objective: Repetitive concussive brain injury (CBI) is associated with cognitive alterations and increased risk of neurodegenerative disease., Methods: To evaluate the temporal window during which the concussed brain remains vulnerable to a second concussion, anesthetized mice were subjected to either sham injury or single or repetitive CBI (either 3, 5, or 7 days apart) using a clinically relevant model of CBI. Cognitive, vestibular, and sensorimotor function (balance and coordination) were evaluated, and postmortem histological analyses were performed to detect neuronal degeneration, cytoskeletal proteolysis, and axonal injury., Results: No cognitive deficits were observed in sham-injured animals or those concussed once. Mice subjected to a second concussion within 3 or 5 days exhibited significantly impaired cognitive function compared with either sham-injured animals (P < 0.05) or mice receiving a single concussion (P < 0.01). No cognitive deficits were observed when the interconcussion interval was extended to 7 days, suggestive of a transient vulnerability of the brain during the first 5 days after an initial concussion. Although all concussed mice showed transient motor deficits, vestibulomotor dysfunction was more pronounced in the group that sustained two concussions 3 days apart (P < 0.01 compared with all other groups). Although scattered degenerating neurons, evidence of cytoskeletal damage, and axonal injury were detected in selective brain regions between 72 hours and 1 week after injury in all animals sustaining a single concussion, the occurrence of a second concussion 3 days later resulted in significantly greater traumatic axonal injury (P < 0.05) than that resulting from a single CBI., Conclusion: These data suggest that a single concussion is associated with behavioral dysfunction and subcellular alterations that may contribute to a transiently vulnerable state during which a second concussion within 3 to 5 days can lead to exacerbated and more prolonged axonal damage and greater behavioral dysfunction.

Microtubule-associated protein 2 (MAP2) is important for microtubule stability and neural plasticity and appears to be among the most vulnerable of the cytoskeletal proteins under conditions of neuronal injury. To evaluate the acute effects of moderate severity traumatic brain injury on MAP2, anesthetized, adult male C57BL/6 mice were subjected to controlled cortical impact brain injury. At 5 min, 15 min, 90 min, 4 h, and 24 h following brain injury (n = 4 injured and n = 1 sham-injured per time point), mice were sacrificed and immunohistochemistry was performed on coronal brain sections. Profound decreases in MAP2 immunolabeling were observed in the ipsilateral cortex and hippocampal dentate hilus at 5 min postinjury and in the ipsilateral hippocampal CA3 area by 4 h postinjury. Decreases in MAP2 labeling occurred prior to notable neuronal cell loss. Interestingly, cortical MAP2 immunoreactivity returned by 90 min postinjury, but the recovery was short-lived within the core in comparison to the periphery of the impact site. Partial restoration of MAP2 immunoreactivity was also observed in the ipsilateral CA3 and dentate hilus by 24 h postinjury. Our data corroborate that MAP2 is an early and sensitive marker for neuronal damage following traumatic brain injury. Acute MAP2 loss, however, may not necessarily presage neuronal death, even following moderate severity traumatic brain injury. Rather, to the best of our knowledge, our data are the first to suggest an intrinsic ability of the traumatized brain for MAP2 recovery after injury of moderate severity.

Objective: Using the neural stem cell (NSC) clone C17.2, we evaluated the ability of transplanted murine NSCs to attenuate cognitive and neurological motor deficits after traumatic brain injury., Methods: Nonimmunosuppressed C57BL/6 mice (n = 65) were anesthetized and subjected to lateral controlled cortical impact brain injury (n = 52) or surgery without injury (sham operation group, n = 13). At 3 days postinjury, all brain-injured animals were reanesthetized and randomized to receive stereotactic injection of NSCs or control cells (human embryonic kidney cells) into the cortex-hippocampus interface in either the ipsilateral or the contralateral hemisphere. One group of animals (n = 7) was killed at either 1 or 3 weeks postinjury to assess NSC survival in the acute posttraumatic period. Motor function was evaluated at weekly intervals for 12 weeks in the remaining animals, and cognitive (i.e., learning) deficits were assessed at 3 and 12 weeks after transplantation., Results: Brain-injured animals that received either ipsilateral or contralateral NSC transplants showed significantly improved motor function in selected tests as compared with human embryonic kidney cell-transplanted animals during the 12-week observation period. Cognitive dysfunction was unaffected by transplantation at either 3 or 12 weeks postinjury. Histological analyses showed that NSCs survive for as long as 13 weeks after transplantation and were detected in the hippocampus and/or cortical areas adjacent to the injury cavity. At 13 weeks, the NSCs transplanted ipsilateral to the impact site expressed neuronal (NeuN) or astrocytic (glial fibrillary acidic protein) markers but not markers of oligodendrocytes (2'3'cyclic nucleotide 3'-phosphodiesterase), whereas the contralaterally transplanted NSCs expressed neuronal but not glial markers (double-labeled immunofluorescence and confocal microscopy)., Conclusion: These data suggest that transplanted NSCs can survive in the traumatically injured brain, differentiate into neurons and/or glia, and attenuate motor dysfunction after traumatic brain injury.

To evaluate the safety of sonar exposure from a neurological perspective, the vulnerability of the central nervous system to underwater exposure with high-intensity, low-frequency sound (HI-LFS) was experimentally examined. Physiological, behavioral and histological parameters were measured in anesthetized, ventilated rats exposed to brief (5 min), underwater HI-LFS. Exposure to 180 dB sound pressure level (SPL) re 1 microPa at 150 Hz (n = 9) did not alter acute cardiovascular physiology (arterial blood pH, pO(2), pCO(2), heart rate, or mean arterial blood pressure) from that found in controls (n = 11). Rats exposed to either 180 dB SPL re 1 microPa at 150 Hz (n = 12) or 194 dB SPL re 1 microPa at 250 Hz (n = 12) exhibited normal cognitive function at 8 and 9 days after sound exposure. Evaluation of neurological motor function revealed a minor deficit 7 days after 180 dB SPL/150 Hz exposure that resolved by 14 days, and no deficits after 194 dB SPL/250 Hz exposure. No overt histological damage was detected in any group. These data suggest that underwater HI-LFS exposure may cause transient, mild motor dysfunction.

In the present investigation, regional ATP, glucose, and lactate contents were examined in the cortical and subcortical structures after cold lesion in rats. Bioluminescence imaging of ATP, glucose, and lactate was performed in serial tissue sections at 4 h (n = 4), 12 h (n = 4) and 24 h (n = 4) after cold injury or sham surgery. Bioluminescence images were analyzed by computer-assisted densitometry, at the lesion site, in cortical areas, in the hippocampus, and in the thalamus. ATP and glucose content were significantly decreased at the lesion site as well as on the contralateral side after 4, 12, and 24 h postinjury Lactate content increased significantly in the hippocampal area on the ipsilateral side at 12 h. Cortical lactate was bilaterally unchanged. The cold lesion injury led to a characteristic ischemic profile in the hippocampus signaled by low ATP and glucose content paralleled by high lactate levels. The otherwise global depletion of glucose and ATP suggests that other factors besides cerebral blood flow may contribute to the impairment of energy metabolism.

Neurofilaments (NF), the intermediate filaments of the neuronal cytoskeleton, provide mechanical stability to the cell. High-molecular-weight NF (NFH) comprises a heavily phosphorylated carboxyl terminal ("sidearm") domain which helps determine interfilament spacing distances. Experimental evidence suggests that dephosphorylation greatly increases the rate and extent of proteolysis of NFH. Because NF proteolysis has been implicated as one pathogenic mechanism underlying cell death following traumatic brain injury (TBI), we analyzed the patterns of acute NFH damage in relation to phosphorylation state following focal, concussive, controlled cortical impact (CCI) brain injury in mice. Brains from C57BL/6 male mice (n = 4 injured and n = 1 sham per time point) were evaluated 5 min, 15 min, 90 min, 4 h, and 24 h following CCI injury (1 mm depth, 5 m/s). Immunohistochemistry was performed using antibodies that recognize epitopes on either dephosphorylated (d-NFH) or phosphorylated (p-NFH) sidearms or on the core (c-NFH) domain. As early as 5-15 min postinjury, immunoreactivity for d-, p-, and c-NFH decreased in the ipsilateral cortex, and hippocampal CA3, CA1, and dentate areas. This marked decrease of NFH labeling occurred in the absence of notable cell loss. Furthermore, partial recovery of NFH labeling was observed as early as 90 min postinjury in the cortex and by 24 h postinjury in hippocampal CA3 and dentate. The results of this study suggest that both phosphorylated and dephosphorylated NFH are vulnerable almost immediately following focal brain injury in mice, but that injured neurons may have an adaptive capability to partially restore this important cytoskeletal protein., (Copyright 2002 Elsevier Science (USA).)

Surgical treatment of fractures of adolescents is often difficult as the epiphyses are still open or not yet completely closed. The osteosynthesis chosen has to consider the remaining prospective growth of the affected bone and biomechanical needs. Due to high physical maturity with small remaining growth capacity in adolescents, a number of different techniques known from osteosynthesis in adults with minor modifications can be used to treat these fractures.

Object: Mild, traumatic repetitive head injury (RHI) leads to neurobehavioral impairment and is associated with the early onset of neurodegenerative disease. The authors developed an animal model to investigate the behavioral and pathological changes associated with RHI., Methods: Adult male C57BL/6 mice were subjected to a single injury (43 mice), repetitive injury (two injuries 24 hours apart; 49 mice), or no impact (36 mice). Cognitive function was assessed using the Morris water maze test, and neurological motor function was evaluated using a battery of neuroscore, rotarod, and rotating pole tests. The animals were also evaluated for cardiovascular changes, blood-brain barrier (BBB) breakdown, traumatic axonal injury, and neurodegenerative and histopathological changes between 1 day and 56 days after brain trauma. No cognitive dysfunction was detected in any group. The single-impact group showed mild impairment according to the neuroscore test at only 3 days postinjury, whereas RHI caused pronounced deficits at 3 days and 7 days following the second injury. Moreover, RHI led to functional impairment during the rotarod and rotating pole tests that was not observed in any animal after a single impact. Small areas of cortical BBB breakdown and axonal injury. observed after a single brain injury, were profoundly exacerbated after RHI. Immunohistochemical staining for microtubule-associated protein-2 revealed marked regional loss of immunoreactivity only in animals subjected to RHI. No deposits of beta-amyloid or tau were observed in any brain-injured animal., Conclusions: On the basis of their results, the authors suggest that the brain has an increased vulnerability to a second traumatic insult for at least 24 hours following an initial episode of mild brain trauma.

The mechanisms underlying secondary cell death after traumatic brain injury (TBI) are poorly understood. Animal models of TBI recapitulate many clinical and pathologic aspects of human head injury, and the development of genetically engineered animals has offered the opportunity to investigate the specific molecular and cellular mechanisms associated with cell dysfunction and death after TBI, allowing for the evaluation of specific cause-effect relations and mechanistic hypotheses. This article represents a compendium of the current literature using genetically engineered mice in studies designed to better understand the posttraumatic inflammatory response, the mechanisms underlying DNA damage, repair, and cell death, and the link between TBI and neurodegenerative diseases.

Considerable effort has led to an increased interest in emerging preclinical and clinical data regarding the pathophysiological changes in the posttraumatic brain. It is widely believed that delayed cell damage and death contributes to behavioral impairment following traumatic brain injury. However, no drug therapy to attenuate this process is available at present, and the development of new therapeutic regimen is urgently warranted. This manuscript represents a compendium of recent preclinical work undertaken to evaluate new pharmacologic strategies in the experimental setting as a first step towards the development of a therapeutic armamentarium directed to improve functional recovery in head-injured patients.

One and a half to two million people sustain a traumatic brain injury (TBI) in the US each year, of which approx 70,000-90,000 will suffer from long-term disability with dramatic impacts on their own and their families' lives and enormous socio-economic costs. Brain damage following traumatic injury is a result of direct (immediate mechanical disruption of brain tissue, or primary injury) and indirect (secondary or delayed) mechanisms. These secondary mechanisms involve the initiation of an acute inflammatory response, including breakdown of the blood-brain barrier (BBB), edema formation and swelling, infiltration of peripheral blood cells and activation of resident immunocompetent cells, as well as the intrathecal release of numerous immune mediators such as interleukins and chemotactic factors. An overview over the inflammatory response to trauma as observed in clinical and in experimental TBI is presented in this review. The possibly harmful/beneficial sequelae of post-traumatic inflammation in the central nervous system (CNS) are discussed using three model mediators of inflammation in the brain, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and transforming growth factor-beta (TGF-beta). While the former two may act as important mediators for the initiation and the support of post-traumatic inflammation, thus causing additional cell death and neurologic dysfunction, they may also pave the way for reparative processes. TGF-beta, on the other hand, is a potent anti-inflammatory agent, which may also have some deleterious long-term effects in the injured brain. The implications of this duality of the post-traumatic inflammatory response for the treatment of brain-injured patients using anti-inflammatory strategies are discussed.

Large-conductance, calcium-activated potassium (maxi-K) channels regulate neurotransmitter release and neuronal excitability, and openers of these channels have been shown to be neuroprotective in models of cerebral ischemia. The authors evaluated the effects of postinjury systemic administration of the maxi-K channel opener, BMS-204352, on behavioral and histologic outcome after lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Anesthetized Sprague-Dawley rats (n = 142) were subjected to moderate FP brain injury (n = 88) or surgery without injury (n = 54) and were randomized to receive a bolus of 0.1 mg/kg BMS-204352 (n = 26, injured; n = 18, sham), 0.03 mg/kg BMS-204352 (n = 25, injured; n = 18, sham), or 2% dimethyl sulfoxide (DMSO) in polyethylene glycol (vehicle, n = 27, injured; n = 18, sham) at 10 minutes postinjury. One group of rats was tested for memory retention (Morris water maze) at 42 hours postinjury, then killed for evaluation of regional cerebral edema. A second group of injured/sham rats was assessed for neurologic motor function from 48 hours to 2 weeks postinjury and cortical lesion area. Administration of 0.1 mg/kg BMS-204352 improved neurologic motor function at 1 and 2 weeks postinjury (P < 0.05) and reduced the extent of cerebral edema in the ipsilateral hippocampus, thalamus, and adjacent cortex (P < 0.05). Administration of 0.03 mg/kg BMS-204352 significantly reduced cerebral edema in the ipsilateral thalamus (P < 0.05). No effects on cognitive function or cortical tissue loss were observed with either dose. These results suggest that the novel maxi-K channel opener BMS-204352 may be selectively beneficial in the treatment of experimental TBI.

A short review of the most widely used and popular experimental models of traumatic brain injury is presented. This review focuses on current animal models of traumatic brain injury that apply mechanical energy to the skull or, after trephination of the skull, to the intact dura. Recent experimental studies evaluating the pathobiology of traumatic brain injury using these models are also discussed. This article attempts to provide a broad overview of current knowledge and controversies in experimental animal research on brain trauma.