Vascular Injury During Lumbar Disc Surgery: Case Report.

A retroperitoneal organ injury-vascular injury or solid organ injury-that occurs during lumbar disc surgery needs to be dealt with adequately, because otherwise it could result in a poor (or, even, fatal) outcome of a "simple" procedure. Vascular injuries require special attention from the neurosurgical side (think of the possibility!) and cooperation between neurosurgeons and abdominal/vascular surgeons. In the presented case of a very obese female patient, a bite injury of the aorta during L3/4 disc surgery led to delayed intra-abdominal hemorrhage, which then required an emergency abdominal operation followed by major thromboembolic complication, and ultimately resulted in amputation of the patient's healthy leg. Pitfalls in intraoperative diagnosis and postoperative care are discussed, along with related medicolegal issues.

The importance of social relationships for brain tumor patients' quality of life: A case for the inclusion of the concept of disclosure in psycho-oncological care.

Purpose: Interpersonal factors are of major importance for cancer patients' physical and mental health. Brain tumor patients rank amongst those cancer patients with the highest psychosocial burden. Changes in language, cognition, and personality pose specific risk factors for impeding interpersonal functioning in this patient group. Despite this, role and relevance of social support including both supportive (e.g., emotional support) and detrimental interactions causing distress (e.g., critical remarks) are not well understood. Aims of this study were thus (1) to investigate the association of social support and patients' Health Related Quality of Life (HRQoL) and (2) to assess whether this relationship is mediated by the patients' disclosure behavior.Methods: Seventy-four ambulatory brain tumor patients (mean age 54 years; 58% women) completed the following self-report questionnaires: Illness-specific Social Support Scale (SSUK) for assessment of positive support and detrimental interactions, the Disclosure of Trauma Questionnaire (DTQ) for assessment of patients' disclosure behavior, and the Short-Form Health Survey (SF-8) for assessment of QoL.Findings: Detrimental social interactions were significantly related to patients' mental and physical well-being while positive support was not. Our results support a model in which patients perceiving detrimental social interactions show more difficulties in talking about illness-specific contents in a functional manner. This, in turn, was associated with a lower physical and mental HRQoL.Conclusions: This was the first study in which the close associations of detrimental social interactions, brain tumor patients' dysfunctional disclosure behavior and patients' mental as well as physical well-being were empiricially validated. Thus, dysfunctional disclosure behavior might pose a relevant therapeutic target when offering psycho-oncological support for brain tumor patients and their families.

Linking pre-existing biorepositories for medical research: the PopGen 2.0 Network.

The significance of human biorepositories for modern medical research, particularly for comprehensive population-based genetic analyses, is constantly growing. While large and centralized institutions are usually considered best suited to meet the increasing demand for high-quality "biobanks," most medical research institutions still host rather heterogeneous and fragmented biobanking activities, undertaken by clinical departments with oftentimes rather different scientific scope. Undoubtedly, most clinicians and medical researchers would appreciate infrastructural support in terms of the storage and handling of their biosamples, but they are also likely to expect access to their samples avoiding extensive formal requirements. We report on the establishment of the PopGen 2.0 Network (P2N), an overarching alliance of initially seven biobanks from Northern Germany which adopted a joint but lean governance structure and use-and-access policy for their samples and data. In addition, the members of P2N have pursued an intense collaboration on ethical, legal and social issues and maintain a common IT infrastructure. The implementation of P2N has substantially improved the prospects of biobank-based research at the participating institutions. The network may thus serve as a role model for similar initiatives geared at linking pre-existing biorepositories for the benefit of research quality, efficiency, and transparency.

Social cognition in patients with intracranial tumors: do we forget something in the routine neuropsychological examination?

PURPOSE: Social cognitive functions are of high clinical relevance. To date, little is known about social cognition in neurooncological patients and this domain is usually not included in standardized neurocognitive test batteries. Aim of this study was thus to assess whether social cognition could pose a useful contribution to the neurocognitive assessment in patients with intracranial tumors. METHODS: We included 30 preoperative patients with a brain tumor. Patients completed a comprehensive test battery for assessment of social cognition. Thirty healthy participants matched for age, gender, and education, served as control group. Clinical relevance of social cognitive deficits was assessed via various self-report measures as well as a clinical rating scale assessing social and occupational functioning. RESULTS: Twenty-five patients (83%) were impaired in at least one measure of social cognition. Whereas patients with lesions to the temporal lobes were most severely impaired, deficits occurred in patients with tumors of a variety of localizations, sizes and malignancies. There was some evidence for missing patients' awareness as well as clinical significance of social cognitive deficits in terms of impaired interactional and occupational functioning. By combination of the Faux-Pas and the Eyes-Test, 77% of patients who were impaired in any social cognitive task were detected. CONCLUSIONS: Deficits in social cognition are frequent and clinically relevant in patients with intracranial tumors. The inclusion of social cognitive measures in the routine neuropsychological examination for brain tumor patients might add valuable information about the patient whilst requiring reasonable additional resources.

The programmable shunt-system Codman Medos Hakim: A clinical observation study and review of literature.

OBJECTIVES: Hydrocephalus can be defined as clinically symptomatic dilatation of the internal ventricular system at the expense of brain and blood volume. Shunt insertion is the mainstay of therapy for communicating hydrocephalus. One of the most frequently used valves is the programmable Codman Medos Hakim valve which enables the pressure level to be adjusted from 30 to 200 mmH2O. The problem of functional over- or underdrainage and the associated complications should be significantly reduced if not excluded. Especially in the clinical application of the Codman Medos Hakim Shunt System in hydrocephalus of other etiology only a few studies can be found. This study aims to increase knowledge of both the safety of Codman Medos valves with SiphonGuard in the clinical application as well as the correct choice of the pressure level for different indications. PATIENTS AND METHODS: In this retrospective study, 101 patients were included who underwent surgery with the adjustable "Codman Medos Hakim" valve with "SiphonGuard" between January 2010 and July 2013. We analyzed the patient files and imaging (CCT, cMRT) data. The statistical examinations were performed using the WINStat program for Excel. RESULTS: Our results show that an initial pressure level of 120mmH2O proved to be suitable in all subgroups. After optimization of the initial pressure level 70.3% of the valves (71 valves) had a pressure level of 120mmH2O. Importantly, only in the SAH subgroup the clinical improvement was correlated with a reduction in the measured indices. But in all subgroups a clinical deterioration was associated with an increased ventricular size. CONCLUSION: Overall, the clinical data show that an initial pressure level of 120mmH2O seems to be appropriate for most patients treated in this series. Measured indices from the cranial imaging can provide valuable indications for the presence of a suboptimal valve setting for the individual patient.

Cross-cultural adaptation and psychometric properties of the SCOPA-Sleep-German version.

Aim of the study was the cross-cultural adaptation and validation of the German version of the Scale for Outcomes in Parkinson's disease-Sleep Scale (SCOPA-Sleep) for assessment of night-time sleep problems (NS) and daytime sleepiness (DS). Eighty-three patients with Parkinson's disease completed the SCOPA-Sleep and a multitude of measures for assessment of validity (e.g., PSQI, ESS). Twenty patients completed the SCOPA-Sleep twice within 2 months for assessment of retest reliability. Sixty-four healthy controls were also included for validity estimation. Internal consistency (Cronbach's alpha) was good with coefficients of .801 and .854 for SCOPA-NS and SCOPA-DS, respectively. Test-retest reliability and inter-rater agreement were excellent. Factor analysis revealed two factors, one for each of the subscales NS and DS. Convergent validity was high with correlations of .797 between SCOPA-NS and PSQI, and .679 between SCOPA-DS and ESS. The German version of the SCOPA-Sleep showed good diagnostic accuracy. Optimal cutoff scores were calculated, resulting in an AUC of .908 for NS and of .959 for DS. The German version of the SCOPA-Sleep is a reliable and valid instrument for assessing NS and DS in patients with Parkinson's disease. As diagnostic accuracy is excellent, this scale can be recommended for routine assessment of both NS and DS in PD combined with other standard measures.

Intended cost reduction in laparoscopic appendectomy by introducing the endoloop: a single center experience.

BACKGROUND: Cost reduction measures in medicine are gaining greater importance nowadays, especially in high-volume procedures such as laparoscopic appendectomy (LAE). Currently there are two common methods of dissecting the appendix from the caecal pole: linear stapler and endoloops. The endoloop is the cheaper device but can only be used in uncomplicated cases of appendicitis. Therefore both methods are used in LAE depending on intraoperative findings. The goal of this study was to retrospectively evaluate possible cost reduction due to increased use of endoloop in LAE in our general surgery department of a tertiary referral university hospital. METHODS: We previously used the stapler for appendix dissection in LAE as our local protocol but introduced the endoloop as standard method in 2015 to reduce intraoperative costs. We conducted a retrospective analysis of patients who underwent LAE between June 2014 and October 2015 in our department. Our purpose is to show the effects on cost reduction during the introductory period adjusting for a potential bias due to the individual learning curve of every surgeon. We estimated costs for LAE by taking into account average device costs and duration of operation (DO) as well as patient outcome. RESULTS: A total of 177 patients underwent LAE, 73 in 2014 (phase I) and 104 in 2015 (phase II). The median DO was 61 (± 24 SD) min during the entire period, and increased by 14 min from phase I to II (from 51 (±23 SD) min to 65 (±24 SD) min respectively, p < 0.001). The use of endoloops increased from 10% to 55% (p < 0.001). Patients' characteristics and outcomes did not differ significantly. A median saving of 5.9€ per operation was calculated in phase II compared to phase I (p = 0.80). CONCLUSION: Introducing the endoloop as standard device for LAE leads to a marginal reduction in intraoperative costs without increasing negative outcomes. In our model the cost-reduction achieved by cheaper devices was overcome by increased costs for DO during the initial phase of use of endoloops. A longer follow up might show a more pronounced cost reduction.

Intraoperative Thresholds for Capsular Stimulation Are Reliable for Chronic Pallidal Deep Brain Stimulation in Dystonia.

BACKGROUND: The threshold current for inducing muscle contractions by stimulation of pyramidal tract fibres adjacent to the globus pallidus internus (GPi) is, besides microelectrode recordings for the determination of nuclear boundaries, currently the only neurophysiological marker for intraoperative refinement of the anatomically planned target point for pallidal deep brain stimulation (GPi-DBS) in dystonia. OBJECTIVES: To determine the relationship between intraoperative thresholds for muscle contractions under general anaesthesia and postoperative thresholds in GPi-DBS. METHODS: Intraoperatively, current amplitude thresholds (120 µs, 130 Hz) were determined in 6 dystonic patients under general anaesthesia (through the uninsulated tip of the microelectrode guide tube). Postoperative localization of chronic stimulation electrodes by MRI and image fusion with the stereotactic planning determined the stimulation contact for comparing thresholds with intraoperative values. RESULTS: Current thresholds were 3.3 ± 0.8 mA intraoperatively (follow-up 0, FU0; n = 12), 2.9 ± 1.2 mA within 1 week after surgery (FU1; n = 12), and 3.5 ± 1.6 mA after 6-17 months (FU2; n = 8). FU0 and FU1 differed by trend, and FU1 and FU2 were significantly different (Friedman test, p = 0.0048; post hoc Dunn multiple comparison test, p < 0.05). FU0 and FU2 were not different. DISCUSSION: The threshold amplitude to induce tonic muscular contractions may constitute a valid approach of functionally refining the anatomically guided electrode placement in GPi-DBS for dystonia, because intraoperative values are predictive for postoperative thresholds with the chronically implanted neurostimulation system.

Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

Targeting of the Subthalamic Nucleus for Deep Brain Stimulation: A Survey Among Parkinson Disease Specialists.

BACKGROUND: Deep brain stimulation within or adjacent to the subthalamic nucleus (STN) represents the most common stereotactic procedure performed for Parkinson disease. Better STN imaging is often regarded as a requirement for improving stereotactic targeting. However, it is unclear whether there is consensus about the optimal target. METHODS: To obtain an expert opinion on the site regarded optimal for "STN stimulation," movement disorder specialists were asked to indicate their preferred position for an active contact on hard copies of the Schaltenbrand and Wahren atlas depicting the STN in all 3 planes. This represented an idealized setting, and it mimicked optimal imaging for direct target definition in a perfectly delineated STN. RESULTS: The suggested targets were heterogeneous, although some clustering was observed in the dorsolateral STN and subthalamic area. In particular, in the anteroposterior direction, the intended targets differed to a great extent. Most of the indicated targets are thought to also result in concomitant stimulation of structures adjacent to the STN, including the zona incerta, fields of Forel, and internal capsule. CONCLUSIONS: This survey illustrates that most sites regarded as optimal for STN stimulation are close to each other, but there appears to be no uniform perception of the optimal anatomic target, possibly influencing surgical results. The anatomic sweet zone for STN stimulation needs further specification, as this information is likely to make magnetic resonance imaging-based target definition less variable when applied to individual patients.

"Inverse signaling" of the transmembrane chemokine CXCL16 contributes to proliferative and anti-apoptotic effects in cultured human meningioma cells.

BACKGROUND: Chemokines and their receptors play a decisive role in tumor progression and metastasis. We recently found a new signaling mechanism in malignant glioma cells mediated by transmembrane chemokines that we termed "inverse signaling". According to this hypothesis, soluble (s)-CXCL16 binds to the surface-expressed transmembrane (tm) -CXCL16, and induces signaling and different biological effects in the stimulated cells, so that the transmembrane ligand itself acts as a receptor for its soluble counterpart. Now, we hypothesized that "inverse signaling" via tm-CXCL16 might also take place in meningiomas, a completely different, benign tumor entity. METHODS: We used quantitative reverse-transcription polymerase chain reaction, immunocytochemistry and western blot to detect CXCL16 and CXCR6 in human meningioma cells isolated from 28 human meningiomas. Subsequently, we stimulated cultured human tm-CXCL16-positive, CXCR6-negative meningioma cells with recombinant s-CXCL16 and analyzed binding, signaling and biological effects using RNAi silencing to verify specificity. RESULTS: In fact, cultured human meningioma cells considerably express CXCL16, but substantially lack CXCR6, the only known CXCL16 receptor. These receptor-negative cells could bind s-CXCL16, and responded to s-CXCL16 application with activation of the intracellular kinases ERK1/2 und Akt. As a consequence, we observed increased proliferation and rescue of apoptosis of cultured meningioma cells. Since binding and signaling were abolished by siRNA silencing, we concluded that tm-CXCL16 specifically acts as a receptor for s-CXCL16 also in human meningioma cells. CONCLUSION: These findings underline our recent report on the mechanism of inverse signaling as a broad biological process also observable in more benign tumor cells and contributing to tumor progression.

Stem cell markers in glioma progression and recurrence.

Aggressive cancer cells show histological similarities to embryonic stem cells. As differentiated cells can re-acquire pluripotency and self-renewal by transfection with the transcription factors OCT4, SOX2, KLF4 and MYC, with Nanog as readout for success, we comprehensively investigated their occurrence and frequency in human astrocytomas of different malignancy grades, primary and matched recurrent glioblastomas, short- and long-term glioblastoma cultures and glioma cell lines. Among astrocytomas, mRNA expression of OCT4, MYC and (less robust) KLF4 increased with malignancy, while in recurrent glioblastomas MYC expression slightly decreased. Correlation analysis revealed distinct positive correlation between distinct stem cell markers, and this effect was most prominent in the recurrent glioblastoma cohort. In situ, embryonic stem cell factors were found also in more differentiated tumor regions. Respective cells were rarely actively proliferating and showed single or combined expression signatures, which, at least in parts, corresponded to observed positive correlations of mRNA expression. However, a 'master-marker' defining the complete glioma stem cell subset could not be confirmed. In glioma cell lines, long- and short-term cultures, embryonic markers were detected at comparable levels. Upon exposure to temozolomide, increased expression of KLF4 (and lesser Nanog and OCT4) was observed. Experimental intrinsic overexpression of SOX2, KLF4 or OCT4 did not affect the other stem cell factors. The embryonic stem cell factors comprehensively investigated in this project can control self-renewal and pluripotency, and therefore tumorigenicity. They should be considered for the development of future diagnostic and therapeutic strategies.

Differential expression of CXCR4 and CXCR7 with various stem cell markers in paired human primary and recurrent glioblastomas.

The chemokine CXCL12 (also termed SDF-1, stromal cell-derived factor-1) and its receptors CXCR4 and CXCR7 are known to play a pivotal role in tumor progression including glioblastomas (GBM). Previous investigations focused on the expression and functional roles of CXCR4 and CXCR7 in different GBM cell subpopulations, but comparative analysis in matched primary versus recurrent GBM samples are still lacking. Thus, here we investigated the expression of CXCR4 and CXCR7 on mRNA and protein level using matched primary and recurrent GBM pairs. Additionally, as GBM CXCR4-positive stem-like cells are supposed to give rise to recurrence, we compared the expression of both receptors in primary and recurrent GBM cells expressing either neural (MUSASHI-1) or embryonic stem cell markers (KLF-4, OCT-4, SOX-2, NANOG). We were able to show that both CXCR4 and CXCR7 were expressed at considerable mRNA and protein levels. CXCR7 was downregulated in relapse cases, and different groups regarding CXCR4/CXCR7 expression differences between primary and recurrent samples could be distinguished. A co-expression of both receptors was rare. In line with this, CXCR4 was co-expressed with all investigated neural and embryonic stem cell markers in both primary and recurrent tissues, whereas CXCR7 was mostly found on stem cell marker-negative cells, but was co-expressed with KLF-4 on a distinct GBM cell subpopulation. These results point to an individual role of CXCR4 and CXCR7 in stem cell marker-positive GBM cells in glioma progression and underline the opportunity to develop new therapeutic tools for GBM intervention.

Intracranial Meningiomas: A 30-Year Experience and Literature Review.

Intracranial meningiomas are tumors arising from the covering cells of the arachnoid layer of the dura mater or from the intraventricular choroid plexus. While mostly benign tumors, they still represent a major challenge to neurosurgeons and other medical disciplines involved in their diagnostic and therapeutic management. Although this review intends to give some state-of-the-art information from the literature, it is mainly based on personal experiences since more than 30 years caring for more than 1500 meningioma patients and point to a few new strategies to further improve on patient outcome.Diagnostics are based on magnetic resonance imaging which shows the relationship between tumor and surrounding intracranial structures, particularly the brain but also the vasculature and to some extent the cranial nerves. Furthermore, it may suggest the grading of the tumor and is very helpful in the postoperative diagnosis of complications and later follow-up course.Surgery still is the main treatment with the aim to completely remove the tumor; also in cases of recurrence, other additional options include radiotherapy and radiosurgery for incompletely removed or recurrent meningiomas. Postoperative chemotherapy has not been shown to provide substantial benefit to the patient especially in highly malignant meningiomas.All therapy options should be intended to provide the patient with the best possible functional outcome. Patients' perspective is not always equivalent to surgeons' perspectives. Neuropsychological evaluation and additional guidance of patients harboring meningiomas have proven to be important in modern neurosurgical intracranial tumor treatment. Their help beyond neurosurgical care facilitates the patients to lead an independent postoperative life.

Factors influencing the outcome (GOS) in reconstructive cranioplasty.

After performing a decompressive craniectomy, a cranioplastic surgery is usually warranted. The complications of this reconstructive procedure may differ from the initial operation. The authors of this study report on their experience to define patient-specific and procedural risk factors for possible complications following cranioplasty influencing the outcome (Glasgow Outcome Scale (GOS)), mobility, shunt dependency, and seizures. A retrospective analysis of 263 patients of all ages and both sexes who had undergone cranioplasty after craniectomy for traumatic brain injury (including chronic subdural hematoma), subarachnoidal hemorrhage (including intracerebral hemorrhage), ischemic stroke, and tumor surgery in one single center in 12 years from January 2000 to March 2012 has been carried out. A multiple logistic regression analysis was performed to identify potential risk factors (age, gender, used cranioplasty material, initial diagnosis, clipped or coil-embolized subarachnoidal hemorrhage (SAH) patients, time interval, complications especially hydrocephalus and seizures, mobility) upon the prognosis described as a dichotomized Glasgow Outcome Scale. Two hundred forty-eight patients met the study criteria. The overall complication rate after cranioplastic surgery was 18.5% (46 patients). Complications included: surgical site infection, epidural hematoma, hydrocephalus with or without former SAH, and new-onset seizures. Logistic regression analysis identified significant correlation between a low GOS (2 or 3) and postoperative seizures (OR 2.37, CI 1.35-4.18, p < 0.05), shunt-depending hydrocephalus (OR 5.83, CI 3.06-11.11, p < 0.05), and age between 51 and 70 years (OR 2.4, 95% CI 1.09-5.29, p = 0.029). However, gender, time interval between craniectomy and cranioplasty, initial diagnosis, and used cranioplasty material had no significant influence on post-cranioplasty complications as surgical site infections, hematoma, wound healing disturbance, seizures, or hydrocephalus. Evaluation of treatment modality in aneurysmal SAH clip vs. coil showed no significant relation to postoperative complications either. Complications after cranioplastic surgery are a common problem, as prognostic factors could identify a shunt-depending hydrocephalus and epilepsia to develop a major deficit after cranioplastic surgery (GOS 2 or 3). We detected a significant extra risk of people between the age of 51 and 70 years to end up in GOS level 2 or 3.

A novel simple measure correlates to the outcome in 57 patients with intracerebellar hematomas. Results of a retrospective analysis.

BACKGROUND: The incidence of intracerebellar hemorrhages approaches 5-10% of all intracerebral hematomas. The clinical presentation varies from headaches and dizziness to rapid deterioration of consciousness to the point of coma in severe cases. In order to find some concrete criteria that could influence the prognosis of these patients, we performed this retrospective study. METHODS: We retrospectively analyzed the factors influencing the outcome of 57 patients with intracerebellar hematomas treated in our clinic in the last 7 years. The Glasgow Coma Scale (GCS) on admission, as well as other parameters as hypertension, diabetes mellitus, presence of malign tumors in the medical history, or the intake of anticoagulants were assessed as independent factors influencing the outcome of the patients. On the other hand, various computed tomography parameters on admission were also correlated with the clinical outcome such as, tight posterior fossa (TPF), volume of the hematoma, hydrocephalus, compression of the fourth ventricle, intraventricular bleeding, as well as the ratio of the maximal width of the hematoma in comparison to the width of the PF were taken into consideration. RESULTS: The results of the study showed that patients with poor GCS on admission had also a poor Glasgow Outcome Score. Interestingly there was a statistically significant correlation between the maximal width of the hematoma in comparison to the width of the PF and the outcome of the patients. It could be also shown that the patients with intraventricular hemorrhage, hydrocephalus, compression of the fourth ventricle over 50% of its maximal width and TPF, had a poor clinical outcome. Moreover, there was a statistically significant correlation of the volume of the hematoma and a poor clinical outcome. CONCLUSIONS: We introduced as a new factor that is, the cerebellar hemorrhage/PF ratio and found out that the value >35% was associated to an unfavorable outcome.

Epithelial-to-mesenchymal transition in paired human primary and recurrent glioblastomas.

Patients with highly malignant glioblastomas have a short median survival time mainly due to aggressive relapses after therapeutic treatment. Beside others, they achieve their progressive character via epithelial-to-mesenchymal transition (EMT). However, comprehensive investigations on EMT in paired primary-recurrent glioblastoma pairs are presently not available. Thus, in our present study we examined the expression profile of different EMT-markers in 17 matched primary and recurrent glioblastomas by qPCR and double-immunofluorescence stainings to identify EMT marker expressing cell types. Additionally, we analyzed the influence of temozolomide on EMT marker expression in vitro. In comparison to primary tumors, expression of ß-catenin (p<0.05), Snail1 (p<0.05), Snail2/Slug (p<0.05), biglycan (p<0.05) and Twist1 (p<0.01) was downregulated in recurrence whereas L1CAM showed upregulation (p<0.05; qPCR). Expression of desmoplakin, vimentin, fibronectin and TGF-ß1 with its receptors TGF-ßR1 and TGF-ßR2 was almost unchanged. Comparing each individual pair, five different 'EMT groups' within our glioblastoma collective were identified according to the regulation of mRNA expression of GFAP, desmoplakin, Snail1, Snail2, Twist1 and vimentin. Additionally, double-stainings of EMT markers in combination with cell specific markers (glial fibrillary acidic protein, CD11b, von Willebrand factor) revealed that EMT markers were expressed in a complex pattern with all three cellular types as possible sources. Temozolomide treatment significantly induced mRNA expression of nearly all investigated EMT markers in T98G glioma cells. Thus, EMT seems to be involved in glioma progression in a complex way requiring an individualized analysis, and is influenced by commonly used therapeutic options in glioma therapy.

Impact of chemokines on the properties of spinal cord-derived neural progenitor cells in a rat spinal cord lesion model.

The existence of endogenous neural progenitor cells (NPCs) in the adult spinal cord (sc) provides the potential for tailored repair therapies after spinal cord injury (SCI). This study investigates the impact of inflammatory mediators on properties of NPC cultures derived from adult rats after SCI. The Infinite Horizon impactor was used to apply 200-kdyn thoracic sc lesions in adult rats. Control groups received laminectomies to equivalent sc regions. Thoracic sc segments were taken for neurosphere cell cultures. Cell proliferation was found to be significantly higher in lesion groups. Neurosphere-derived cells differentiated into neurons, oligodendroglia, and astroglia. Lesion cultures exhibited significantly higher amounts of glial fibrillary acidic protein (GFAP) mRNA (P < 0.0005) and ß-III-tubulin mRNA (P < 0.05) compared with sham animals. Neurospheres from different treatment groups exhibited the same amounts of tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 mRNA. C-C chemokine receptor (CCR) expression on neurospheres was examined by real-time RT-PCR. CCR1 was expressed most consistently in mRNA levels in neurospheres from both treatment groups. After cell differentiation, CCR1 mRNA amounts decreased. CCR1 was detectable by immunohistochemistry in neurospheres and differentiated cells of both groups. Application of CCL3 during differentiation cycles led to significantly higher GFAP mRNA amounts in sham animals compared with CCL3-free cultures; in contrast, CCL3 had no impact on cell differentiation in the lesion group. In conclusion, impact SCI alters differentiation tendencies and proliferation rates of adult-derived sc NPCs. Thereby, CCR1/CCL3 promotes specifically astroglial differentiation of NPCs, which provides a potential target for future neurorestorative approaches.