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Abstract: Approximately 4000 human beings experience a traumatic brain injury each day in the United States ranging in severity from mild to fatal. Improvements in initial management, surgical treatment, and neurointensive care have resulted in a better prognosis for traumatic brain injury patients but, to date, there is no available pharmaceutical treatment with proven efficacy, and prevention is the major protective strategy. Many patients are left with disabling changes in cognition, motor function, and personality. Over the past two decades, a number of experimental laboratories have attempted to develop novel and innovative ways to replicate, in animal models, the different aspects of this heterogenous clinical paradigm to better understand and treat patients after traumatic brain injury. Although several clinically-relevant but different experimental models have been developed to reproduce specific characteristics of human traumatic brain injury, its heterogeneity does not allow one single model to reproduce the entire spectrum of events that may occur. The use of these models has resulted in an increased understanding of the pathophysiology of traumatic brain injury, including changes in molecular and cellular pathways and neurobehavioral outcomes. This review provides an up-to-date and critical analysis of the existing models of traumatic brain injury with a view toward guiding and improving future research endeavors. [Copyright &y& Elsevier]

Background: In recent years a wide variety of strategies to treat the haemodynamically unstable patient with pelvic ring fractures have been proposed. This study evaluates our institutional management of patients with severe pelvic fractures and analyses their outcomes., Methods: Retrospective review of all severely injured trauma patients with pelvic ring injuries admitted to a level I trauma centre from 2007 to 2012. Patient records were documented prospectively in a trauma database and evaluation was performed by SPSS., Results: During the study period, a total of 173 patients with pelvic ring fractures were admitted and formed the basis of this study. Overall, 46% of the patients had suffered a type A fracture, 25% a type B fracture and the remaining 29% a type C pelvic ring fracture. Surgical treatment was required in 21% of the patients (pelvic C-clamp, n = 6; supra-acetabular external fixator, n = 32; pelvic packing, n = 12; definitive plate osteosynthesis of the pubis symphysis, n = 6). Angio-embolization was performed in 16 patients (9%); in 8 patients it was the only specific treatment for the pelvic injury on day 0 and in 8 patients it was performed immediately post-operatively. The overall mortality rate was 12.7% (n = 22), with the type C pelvic fractures having the highest mortality (30.0%). Four patients died immediately after admission in the shock room., Conclusions: Angiographic embolization as a first-line treatment was only performed in haemodynamically stable patients or in patients responding to fluid resuscitation with the finding of an arterial blush in the CT scan. In haemodynamically unstable patients, pre-peritoneal pelvic packing in combination with mechanical pelvic stabilization was immediately carried out, followed by angio-embolization post-operatively if signs of persistent bleeding remained present., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Outcome after traumatic brain injury (TBI) in the elderly has not been fully elucidated. The present retrospective observational study investigates the age-dependent outcome of patients suffering from severe isolated TBI with regard to operative and non-operative treatment. Data were prospectively collected in the TraumaRegister DGU. Anonymous datasets of 8629 patients with isolated severe blunt TBI (AISHead≥3, AISBody≤1) documented from 2002 to 2011 were analysed. Patients were grouped according to age: 1-17, 18-59, 60-69, 70-79 and ≥80 years. Cranial fractures (44.8%) and subdural haematomas (42.6%) were the most common TBIs. Independent from the type of TBI the group of patients with operative treatment declined with rising age. Subgroup analysis of patients with critical TBI (AISHead=5) revealed standardised mortality ratios (SMRs) of 0.81 (95% CI 0.75-0.87) in case of operative treatment (n=1201) and 1.13 (95% CI 1.09-1.18) in case of non-operative treatment (n=1096). All age groups ≥60 years showed significantly reduced SMRs in case of operative treatment. Across all age groups the group of patients with low/moderate disability according to the GOS (4 or 5 points) was higher in case of operative treatment. Results of this retrospective observational study have to be interpreted cautiously. However, good outcome after TBI with severe space-occupying haemorrhage is more frequent in patients with operative treatment across all age groups. Age alone should not be the reason for limited care or denial of operative intervention., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: The optimal treatment of intervertebral disk lesions accompanying thoracolumbar fractures remains controversial. To evaluate short- and medium-term progression of intervertebral disk lesions accompanying vertebral fractures, MRI scans obtained after trauma were compared with scans obtained at an average follow-up of 1 year, by means of our clinically useful classification of traumatic intervertebral disk lesions., Materials and Methods: MRI scans of 54 disks in patients with trauma-induced single-level thoracolumbar fractures were analyzed retrospectively. All patients underwent posterior stabilization using a titanium internal fixator. Exclusion criteria were malignant vertebral collapse, spondylodiskitis, osteoporotic fractures, and degenerative disk disease in the uninjured disks. Morphologic changes and signal alterations of the adjacent disks were compared using routine MRI scans obtained after trauma and at an average follow-up of 1 year. Disks were divided according to their signals into four categories, from grade 0 to grade 3., Results: Of the disks studied after trauma (n = 54), 27.8% were determined to be grade 0, 31.5% were grade 2, and 40.7% were grade 3. In the follow-up examination, MRI detected grade 0 in 13% of disks. Hence, more than 50% of the disks with grade 0 after trauma changed into grade 2 lesions, resulting in 46.3% grade 2 lesions. Grade 3 disk lesions (40.7%) remained the same without any sign of recovery., Conclusion: In the current study, we found progressive disk degradation and creeping in instrumented and nonfused segments in thoracolumbar fractures. For further validation, randomized controlled long-term outcome investigations seem mandatory as the next step in future clinical research.

Traumatic hemipelvectomy is a severe, however rare injury associated with high lethality. Up to now, immediate surgical completion of the amputation has been recommended as a lifesaving therapy. We present a case of near complete hemipelvectomy with open fracture of the ileosacral joint, wide open symphysis and severe soft tissue trauma including a decollement around the pelvis. Successful complete replantation was performed by primary internal stabilisation and revascularisation using vascular grafts. In the further hospital course, numerous revisions of the soft tissue injury and reconstructive surgery were needed. Thirty months later, the patient's condition is physically and psychologically stable and he is able to walk using crutches. The key point of successful management was skilled emergency damage control surgery followed by dedicated surgical care to avoid septic complications., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: There are a variety of surgical strategies for the treatment of traumatic thoracolumbar vertebral fractures. There is still no proof for the superiority of any strategy concerning clinical or radiological outcomes. The aim of this study was the evaluation of residual complaints and correlation with radiological findings., Patients and Methods: 87 patients, who underwent different types of surgery for vertebral fractures of the thoracolumbar region were included. Patients were treated by posterior stabilisation with internal fixation alone, by a combined approach using posterior internal fixation and anterior fusion by bone graft from the iliac crest with or without additional anterior plating or with a combined approach using posterior stabilisation and anterior implantation of an expandable titanium cage. Data were collected using results of physical examination, standardised testing of several established quality of life scores (SF-36, VAS, LBOS and Oswestry score) as well as radiological findings (post-traumatic kyphosis, loss of correction)., Results: There was no difference in the overall results of quality of life in the different subgroups. Analysis of the subgroups revealed differences in the complaints according to the surgical strategy used (a high rate of non-fusion where bone grafts, especially without additional anterior plating were used, combined with a high rate of bone graft morbidity, intercostal neuralgia in cage implantation). Loss of correction as documented in the radiological course showed a maximum in patients who underwent posterior stabilisation without an additional anterior approach. There was no correlation of loss of correction and quality of life., Conclusion: Overall outcomes of the four surgical strategies were comparable in our study concerning loss of correction and quality of life, respectively. The use of bone grafts, however, results in a high rate of non-fusion with a remarkable number of patients complaining about bone graft morbidity. Therefore we prefer the use of expandable titanium cages for anterior stabilisation if additional anterior stabilisation is necessary due to type of fracture or damage of adjacent discs. In any other cases, a limited approach by posterior instrumentation alone should be considered., (Georg Thieme Verlag KG Stuttgart · New York.)

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.

Introduction: Liver cirrhosis has been shown to be associated with impaired outcome in patients who underwent elective surgery. We therefore investigated the impact of alcohol abuse and subsequent liver cirrhosis on outcome in multiple trauma patients., Materials and Methods: Using the multi-centre population-based Trauma Registry of the German Society for Trauma Surgery, we retrospectively compared outcome in patients (ISS ≥ 9, ≥ 18) with pre-existing alcohol abuse and liver cirrhosis with healthy trauma victims in univariate and matched-pair analysis. Means were compared using Student's t-test and analysis of variance (ANOVA) and categorical variables using χ(2) (p<0.05=significant)., Results: Overall 13,527 patients met the inclusion criteria and were, thus, analyzed. 713 (5.3%) patients had a documented alcohol abuse and 91 (0.7%) suffered from liver cirrhosis. Patients abusing alcohol and suffering from cirrhosis differed from controls regarding injury pattern, age and outcome. More specific, liver cirrhotic patients showed significantly higher in-hospital mortality than predicted (35% vs. predicted 19%) and increased single- and multi-organ failure rates. While alcohol abuse increased organ failure rates as well this did not affect in-hospital mortality., Conclusions: Patients suffering from liver cirrhosis presented impaired outcome after multiple injuries. Pre-existing condition such as cirrhosis should be implemented in trauma scores to assess the individual mortality risk profile., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Lesions of the intervertebral disk accompanying vertebral fractures are the subject of controversy regarding the extent of surgical intervention, in part due to the lack of a comprehensive classification. The purpose of this study is to present a novel and clinically useful classification system for traumatic disk lesions after vertebral fractures., Materials and Methods: MRI of 204 disks in 102 patients with trauma-induced single-level thoracolumbar fractures referred to our trauma center between 2007 and 2011 were analyzed retrospectively. Exclusion criteria were malignant vertebral collapse, spondylodiskitis, osteoporotic fractures, and degenerative disk disease in the uninjured disks. Morphologic changes and signal alterations of the adjacent disks were determined using routine MRI of these patients and a grading system was developed. Disks were divided according to their signals into four categories from grade 0 to grade 3. Intra- and interobserver reliabilities were measured by calculating the Cohen kappa coefficient., Results: Of the 204 disks studied, 28.9% (59/204) were determined to be grade 0 (uninjured), 4.9% (10/204) grade 1 (disk edema), 25.5% (52/204) grade 2 (bleeding/rupture), and 40.7% (83/204) grade 3 (displacement). The kappa value for the intra- and interobserver agreement was 0.96., Conclusion: This novel classification may improve communication between spine surgeons and radiologists as well as facilitate clinical decision making in spine surgery. Further studies need to be conducted to verify clinical relevance.

Background: Clara cell protein 16 (CC16) has recently gained acceptance as a blood biomarker for detecting direct and indirect lung injury. Although the early elevation of CC16 serum levels has been shown to correlate with pulmonary damage in patients with multiple injuries, the subsequent time course of CC16 serum levels has not been investigated in these patients., Methods: Fifty-eight patients with multiple injuries, 32 with severe thoracic injury, and 12 healthy volunteers were enrolled in this study. CC16 serum levels were measured at the time they were admitted to the trauma ward "time 0" and subsequently until day 14 using the enzyme-linked immunosorbent assay technique. The correlation between CC16 serum levels and severe lung injury, onset of nosocomial pneumonia, acute respiratory distress syndrome or acute lung injury, and organ failure was measured. In addition, areas under the receiver operating characteristic curve were calculated (p < 0.05 = significant)., Results: In patients with lung injury, initial "time 0" median CC16 values were significantly elevated (11.2 ng/mL) compared with patients without severe thoracic injury (6.9 ng/mL) and controls (6.3 ng/mL). The observed elevation in serum CC16 declined to control values within 12 to 24 hours after trauma unless patients secondarily developed pneumonia. In the latter patients, median CC16 serum levels were significantly elevated (14.5 ng/mL) at the onset of pneumonia compared with their levels (7.3 ng/mL) 1 day before. In contrast, no secondary elevation in CC16 serum levels was observed in patients without severe lung injury within the same 24-hour period. The area under the receiver operating characteristic curve for serum CC16 and pneumonia was 0.79 (0.62-0.97; p = 0.0011)., Conclusion: Our results confirm the previously described association between initial elevation in CC16 serum levels and severe thoracic injury in patients with multiple injuries. In addition, we found that the initial elevation in CC16 serum levels declines to control values within the first day after trauma and that a secondary elevation indicates respiratory complications., Level of Evidence: Diagnostic study, level II.

We present a case of a pregnant woman (32nd gestational week) that suffered from a chronic non-healing wound at the distal radius. Skeletal tuberculosis was finally diagnosed and treated successfully with staged surgical therapy combined with appropriate medication. One year after surgical treatment, the outcome of the mother was excellent and the baby did not suffer from any disease related to operative procedures or pharmacotherapy. Operative treatment of skeletal tuberculosis (especially osteoarticular and vertebral tuberculosis) in combination with tuberculostatic therapy during pregnancy and lactation seem to be the appropriate treatment with minimal risk for the child and excellent outcome for the mother.

Injuries to the spinal column and cord in children are a rare condition. Epidemiological data could help to establish an evidence-based assessment and therapy of these patients. We present a retrospective chart analysis of children with spinal injuries who were admitted to the emergency room. The patients were analyzed regarding age, mechanism, and distribution of their injuries to all spinal regions and treatment strategies. Thirty-five children met the inclusion criteria with severe spinal injuries (Abbreviated Injury Scale [AIS] for Region 6 [spine]; AIS region 6) in a period from January 2003 to December 2009. The incidence was extremely low in younger children, with increasing numbers during adolescence. Neurological deficit without fracture accounted for almost 25% of all patients. The majority of patients were treated conservatively; operative treatment was performed in 25% of patients with unstable fractures, particularly in adolescents. Treatment strategies differ according to the type and degree of injury, age, and level of spine maturation.

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.

Conflicting reports exist regarding the quality of prehospital treatment of pediatric trauma patients. The purpose of this investigation was to determine whether prehospital treatment and emergency management in pediatric trauma patients were similar to that in adult patients. All patients who had been prospectively documented in the registry of the German Trauma Society (DGU) between 2002 and 2005 were selected for this study. A total of 312 matched pairs of adult and pediatric patients suffering from identical injuries were defined and compared with respect to cause of trauma, diagnostic and therapeutic interventions, and outcome. Within the study group, 63% were male, and the average age was 10.5+/-2.7 (SD) years in the pediatric group and 33.9+/-9.3 years in the adult group. There was no significant difference regarding prehospital intubation, reanimation, fluid management, chest drainage, ground and air transport to the hospital, time to arrival or interval in the emergency room. In contrast, significant differences (p<0.05) were observed in terms of the cause of trauma and pre-existing diseases. Pediatric trauma patients were not triaged or treated differently from adult trauma patients in respect to key issues of prehospital and early clinical trauma management.

We report on a three-year-old girl who fell accidentally from the fourth floor. She suffered multiple trauma, including severe head injury, unstable T2-T3 Chance fracture, pneumothorax with lung contusion and serial rib fractures on the left side, liver laceration, splenic injury and fracture of the sacral bone on the right side. The progressive intracranial pressure was released by trepanation and bifrontal craniectomy. The abdominal injuries were treated conservatively. After stabilization of the intracranial situation, dorsal spondylodesis from T2 to T4 was performed employing the cannulated NEON system (Ulrich(®)) with CT-controlled positioning of guide wires. One year on, the implants have been removed and the patient has good function, with only a small atactic dysfunction as residuum. To our knowledge, this is the first report of a pediatric Chance fracture located in the upper thoracic spine following a fall from great height that describes how this treatment approach led to a very favorable outcome.

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.

Injury to the spinal column and cord are often part of life-threatening multiple trauma. Epidemiological data could help to establish an evidence-based assessment and therapy of these patients. We present a retrospective chart analysis of 590 multiple traumatized patients admitted within a 4-year-period. Patients suffering from injuries of the spinal column were analysed regarding mechanism and distribution of their injuries to all body regions. Thirty-one percent (n = 183) of polytraumatized patients displayed a spine injury. Distribution analysis showed peaks in the cervical spine and the thoraco-lumbar junction. The risk of relevant associated injuries is mainly influenced from anatomical vicinity to the injured spinal segment. Injuries to the spinal column are frequent in the multiple trauma patients population. Diagnosed injuries to distinct body regions should make the trauma team suspicious of injury to the nearby spinal column. Appropriate treatment includes thorough assessment of all injuries to clarify the damage and carry on special protection of these spinal regions preventing from deterioration.

Treatment of polytrauma patients has been discussed extensively during the past decades. Management in the prehospital phase, on admission, and in the early postoperative/ICU-period has to refer to injury severity, priority of injuries, and likelihood of development of multi organ failure. Cervical spine injuries are reported in 4-34% of polytrauma cases. Securing the cervical spine by a hard collar is one of the basic procedures in the prehospital phase. Different strategies of assessing the cervical spine are still discussed controversially. Since plain radiographs, CT-scan, MRI, and flexion/extension fluoroscopy still play a role in early diagnosis of cervical spine injury, we present an analysis of cervical spine injuries in our multiple trauma patients to elucidate our algorithm. We reviewed our data between January 2003 and December 2006 concerning epidemiology, diagnosis and treatment of cervical spine injury in polytrauma patients. Multislice-CT (MSCT) or Multidetector-CT was used as standard diagnostic procedures in the polytraumatized patient. In 97% of patients, CT-scanning showed to be a reliable tool in detecting injuries of the cervical spine. Only in two patients (3%), additional MRI lead to a change in treatment strategy. Of 66 polytraumatized patients with significant cervical spine injury, 25 (37.9%) received surgical treatment within 24 h. Sixteen patients (24.2%) were treated surgically after stabilization on ICU. There was a better outcome concerning length of hospitalization in the "day-onesurgery" group. We consider MSCT as standard approach towards diagnosis of cervical spine injury in polytrauma patients. MRI and flexion/extension fluoroscopy can give additional information in selected cases.

Age dependent motor unit dedifferentiation is a key component of impaired muscle function in advanced age. Here, we tested the hypothesis that rat muscle histochemical profile during the lifespan of an individual has an age-specific pattern since comprehensive longitudinal studies of muscle differentiation after birth and dedifferentiation in advanced age are scarce. Our results show that extensor digitorum longus muscle (EDL) is comprised only of two fiber types after birth, type slow-oxidative (SO) and type SDH-intermediate (SDH-INT), the latter being indicative for the presence of polyneuronal innervation. In contrast to the constantly growing cross-sectional area of the muscle fibers, a dramatic decrease in SDH-INT proportion occurs between day 14 and 21 after birth resulting in a complete loss of fiber type SDH-INT at the age of 90 days (p<0.05). At the age of 270 days, the fiber type composition of rat EDL dedifferentiates as shown by the reappearance of the SDH-INT type with a further increase at the age of 540 days (p<0.05). These changes in histochemical fiber type spectra are brought about by fiber type conversion within the fast twich fibers. The findings of the present study provide further evidence that fiber type conversion is a basic mechanism leading to motor unit differentiation and dedifferentiation during ontogenesis. Fiber type conversion shows a distinct time specific pattern and is also characteristic for motor unit regeneration after peripheral nerve repair. Factors that influence fiber type conversion and thereby motor unit organization may provide a future therapeutic option to enhance the regenerative capacity of motor units.

The epsilon4 allele of apolipoprotein E (APOE) and traumatic brain injury (TBI) are both risk factors for the development of Alzheimer's disease (AD). These factors may act synergistically, in that APOE4+ individuals are more likely to develop dementia after TBI. Because the mechanism underlying these effects is unclear, we questioned whether APOE4 and TBI interact either through effects on amyloid-beta (Abeta) or by enhancing cell death/tissue injury. We assessed the effects of TBI in PDAPP mice (transgenic mice that develop AD-like pathology) expressing human APOE3 (PDAPP:E3), human APOE4 (PDAPP:E4), or no APOE (PDAPP:E-/-). Mice were subjected to a unilateral cortical impact injury at 9-10 months of age and allowed to survive for 3 months. Abeta load, hippocampal/cortical volumes, and hippocampal CA3 cell loss were quantified using stereological methods. All of the groups contained mice with Abeta-immunoreactive deposits (56% PDAPP:E4, 20% PDAPP:E3, 75% PDAPP:E-/-), but thioflavine-S-positive Abeta (amyloid) was present only in the molecular layer of the dentate gyrus in the PDAPP:E4 mice (44%). In contrast, our previous studies showed that in the absence of TBI, PDAPP:E3 and PDAPP:E4 mice have little to no Abeta deposition at this age. After TBI, all of the Abeta deposits present in PDAPP:E3 and PDAPP:E-/- mice were diffuse plaques. In contrast to the effect of APOE4 on amyloid, PDAPP:E3, PDAPP:E4, and PDAPP:E-/- mice did not differ in the amount of brain tissue or cell loss. These data support the hypothesis that APOE4 influences the neurodegenerative cascade after TBI via an effect on Abeta.

Traumatic brain injury (TBI) increases susceptibility to Alzheimer's disease (AD), but it is not known how TBI contributes to the onset or progression of this common late life dementia. To address this question, we studied neuropathological and behavioral consequences of single versus repetitive mild TBI (mTBI) in transgenic (Tg) mice (Tg2576) that express mutant human Abeta precursor protein, and we demonstrate elevated brain Abeta levels and increased Abeta deposition. Nine-month-old Tg2576 and wild-type mice were subjected to single (n = 15) or repetitive (n = 39) mTBI or sham treatment (n = 37). At 2 d and 9 and 16 weeks after treatment, we assessed brain Abeta deposits and levels in addition to brain and urine isoprostanes generated by lipid peroxidation in these mice. A subset of mice also was studied behaviorally at 16 weeks after injury. Repetitive but not single mTBI increased Abeta deposition as well as levels of Abeta and isoprostanes only in Tg mice, and repetitive mTBI alone induced cognitive impairments but no motor deficits in these mice. This is the first experimental evidence linking TBI to mechanisms of AD by showing that repetitive TBI accelerates brain Abeta accumulation and oxidative stress, which we suggest could work synergistically to promote the onset or drive the progression of AD. Additional insights into the role of TBI in mechanisms of AD pathobiology could lead to strategies for reducing the risk of AD associated with previous episodes of brain trauma and for preventing progressive brain amyloidosis in AD patients.

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.

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.