Outcome of traumatic intervertebral disk lesions after stabilization by internal fixator.

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.

A clinically useful classification of traumatic intervertebral disk lesions.

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.

Circulating levels of Clara cell protein 16 but not surfactant protein D identify and quantify lung damage in patients with multiple injuries.

BACKGROUND: Almost 60% of all patients with severe multiple injuries sustain severe chest trauma with aggravating effect on morbidity and mortality. Diagnosis of lung contusion is performed by early posttraumatic multislice computed tomography. Because this diagnostic procedure requires time, resources, and exposure to radiation, a noninvasive approach with easy follow-up measurements is warranted. METHODS: Serum levels of Clara cell protein 16 (CC16) and surfactant protein D as lung-specific biomarkers were obtained on admission from 104 patients with multiple injuries using enzyme-linked immunosorbent assay technique. Patients were divided into those with severe lung injury ([LI]; n = 68) and without LI (NLI; n = 36). Nonsmoking healthy volunteers served as controls. In addition, volume of lung contusions were calculated planimetrically on serial multislice computed tomography scans obtained after admission. Factors influencing CC16 serum levels were determined in uni- and multivariate analyses, and Spearman rank coefficients were calculated for correlations. RESULTS: Patients with LI showed a significant (p < 0.05) elevation of median CC16 levels (10.2 ng/mL) compared with NLI patients (5.4 ng/mL) and controls (5.2 ng/mL). Serum CC16 levels correlated with the volume of lung contusions (r = 0.78, p < 0.0001) and were not influenced by overall injury severity, age, gender, or preclinical ventilation. In contrast, circulating surfactant protein D levels were not associated with the presence of LI or the extent of lung contusions. CONCLUSIONS: Our results advocate CC16 as a potential biomarker for LI in severely injured patients because of its high correlation with the volume of contused lung parenchyma. Therefore, this parameter may allow a specified initial treatment of patients with multiple injuries.

Outcome after operative treatment of Vancouver type B1 and C periprosthetic femoral fractures: open reduction and internal fixation versus revision arthroplasty.

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.

Suppression and recovery of LPS-stimulated monocyte activity after trauma is correlated with increasing injury severity: a prospective clinical study.

BACKGROUND: Monocytes represent a key immunocompetent cell type, whose functional capacity is profoundly influenced by systemic trauma. Because data on monocyte function in a heterogeneous trauma population, including slightly injured patients, is limited, we evaluated whether the magnitude of monocyte dysfunction can be related with injury severity and is useful as a predictive biomarker for development of systemic inflammatory response syndrome (SIRS) and sepsis. METHODS: Blood samples were obtained from 58 patients at admission to a level 1 Trauma Unit (mean injury severity score [ISS] of 25.7; range 4-75), and daily for five successive days. Monocyte activity was assessed by measuring lipopolysaccharide (LPS)-stimulated interleukin (IL)-1-beta production. Levels of IL-6, IL-10, and procalcitonin were also determined and values were correlated to injury severity and occurrence of SIRS. RESULTS: Even mildly injured individuals (ISS 1-8) showed a significant suppression of the LPS-response directly upon admission (p < 0.05). Both LPS-response (p = 0.049) and IL-6 levels (p = 0.046) were found to be predictive for the presence/diagnosis of SIRS. After minor trauma (ISS 1-8), the LPS-response returned to normal levels by day 2, whereas in more severely injured patients (ISS > or = 25) the suppression of monocyte activity persisted for the duration of the study period. CONCLUSION: The extent of suppression of monocyte function is directly associated with the severity of trauma in both severely injured and patients with minor trauma. Acute posttraumatic changes in monocyte function and IL-6 concentrations were both predictive for the development of SIRS/sepsis. Although monocyte function in mildly injured patients is restored shortly after injury, the observed delay in recovery in severely traumatized patients may critically influence the clinical course.

Periprosthetic humeral fractures after shoulder arthroplasty: operative management and functional outcome.

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.

Changes in cortical and subcortical energy metabolism after repetitive and single controlled cortical impact injury in the mouse.

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.

Biphasic elevation in cerebrospinal fluid and plasma concentrations of endothelin 1 after traumatic brain injury in human patients.

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.

Early versus late onset of multiple organ failure is associated with differing patterns of plasma cytokine biomarker expression and outcome after severe trauma.

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.

Delayed elevation of soluble tumor necrosis factor receptors p75 and p55 in cerebrospinal fluid and plasma after traumatic brain injury.

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.

Repetitive mild brain trauma accelerates Abeta deposition, lipid peroxidation, and cognitive impairment in a transgenic mouse model of Alzheimer amyloidosis.

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.

Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer's disease.

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.

Physiological levels of pro- and anti-inflammatory mediators in cerebrospinal fluid and plasma: a normative study.

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.

The role of angio-embolization in the acute treatment concept of severe pelvic ring injuries.

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.

Aggressive operative treatment of isolated blunt traumatic brain injury in the elderly is associated with favourable outcome.

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.

Changes in regional energy metabolism after cortical cold lesion in the rat brain.

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.

Transient loss of microtubule-associated protein 2 immunoreactivity after moderate brain injury in mice.

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.

Transplanted neural stem cells survive, differentiate, and improve neurological motor function after experimental traumatic brain injury.

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.

Effects of underwater sound exposure on neurological function and brain histology.

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.

Liver cirrhosis but not alcohol abuse is associated with impaired outcome in trauma patients - a retrospective, multicentre study.

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.