Antiepileptic treatment of brain tumor patients mainly depends on the individual physician's ... more Antiepileptic treatment of brain tumor patients mainly depends on the individual physician's choice rather than on well-defined predictive factors. We investigated the predictive value of defined clinical parameters to formulate a model of risk estimations for subpopulations of brain tumor patients. We enclosed 650 patients > 18 years of age who underwent brain tumor surgery and included a number of clinical data. Logistic regressions were performed to determine the effect sizes of seizure-related risk factors and to develop prognostic scores for the occurrence of preoperative and early postoperative seizures. A total of 492 patients (334 gliomas) were eligible for logistic regression for preoperative seizures, and 338 patients for early postoperative seizures. Age ≤ 60 years (odds ratio [OR] = 1.66, p = 0.020), grades I and II glioma (OR = 4.00, p = 0.0002), total tumor/edema volume ≤ 64cm(3) (OR = 2.18, p = 0.0003), and frontal location (OR = 2.28, p = 0.034) demonstrated a...
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 18, 2015
To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour sp... more To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas ...
Tumour resection in the Rolandic region is a challenge. Aim of this study is to review a series o... more Tumour resection in the Rolandic region is a challenge. Aim of this study is to review a series of patients malignant glioma surgery in the Rolandic region which was performed by combinations of neuronavigation, sonography, 5-aminolevulinic acid fluorescence guided (5-ALA) surgery and intraoperative electrophysiological monitoring (IOM). 29 patients suffering malignant gliomas in the motor cortex (17) and sensory cortex (12) were analyzed with respect to functional outcome and grade of resections. Improvement of motor function was seen in 41.5% one week after surgery, 41.5% were stable, only 17% deteriorated. After three months patients had an improvement of motor function in 56%, of Karnofsky Score (KPS) 27% and sensory function was improved in 8%. Deterioration of motor function was seen in 16%, in sensory function 4% and in KPS 28% after three months. 25% showed no residual tumour in early post surgical contrast enhanced MRI. 10% had less than 2% residual tumour and 15% had 2-5% residual tumour. Preoperative functional neuroimaging, neuronavigation for planning the surgical approach and resection margins, intraoperative sonography and 5-ALA guided surgery in combination with the application of IOM shows that functional outcome and total to subtotal resection of malignant glioma in the Rolandic region is feasible.
We analyzed aquaporin 4 and -1 expression in subependymomas, benign and slow growing brain tumors... more We analyzed aquaporin 4 and -1 expression in subependymomas, benign and slow growing brain tumors WHO grade I. Ten subependymoma cases were investigated, five of the fossa inferior and five of the fossa superior. Using immunohistochemistry, we observed different aquaporin expression patterns depending on localization: aquaporin 4 and -1 were detected in infratentorial subependymomas in the entire tumor tissue. In contrast, supratentorial subependymomas revealed aquaporin 4 and -1 expression only in border areas of the tumor. PCR analyses however showed no difference in aquaporin 4 expression between all subependymomas independent of localization but at higher levels than in normal brain. In contrast, aquaporin 1 RNA levels were found to be higher only in infratentorial samples compared to supratentorial and normal brain samples. The reason for the different distribution pattern of aquaporin 4 in subependymomas still remains unclear. On the cellular level, aquaporin 4 was redistributed on the surface of the tumor cells, and in freeze fracture replicas no orthogonal arrays of particles were found. This was similar to our previous findings in malignant glioblastomas. From these studies, we know that extracellular matrix molecules within the tumor like agrin and its receptor alpha-dystroglycan are involved in forming orthogonal arrays of particles. In subependymomas neither agrin nor alpha-dystroglycan were detected around blood vessels. Taken together, we show in this study that in the benign subependymomas aquaporins 1 and 4 are dramatically redistributed and upregulated. We speculate that extracellular environments of infra- and supratentorial subependymomas are different and lead to different distribution patterns of aquaporin 4 and -1.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 9, 2015
To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex viv... more To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after...
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2014
The main water channel in the brain, aquaporin-4 (AQP4) is involved in maintaining homeostasis an... more The main water channel in the brain, aquaporin-4 (AQP4) is involved in maintaining homeostasis and water exchange in the brain. In adult mammalian brains, it is expressed in astrocytes, mainly, and in high densities in the membranes of perivascular and subpial endfeet. Here, we addressed the question how this polarized expression is established during development. We used immunocytochemistry against AQP4, zonula occludens protein-1, glial fibrillary acidic protein, and β-dystroglycan to follow astrocyte development in E15 to P3 NMRI mouse brains, and expression of AQP4. In addition we used freeze-fracture electron microscopy to detect AQP4 in the form of orthogonal arrays of particles (OAPs) on the ultrastructural level. We analyzed ventral, lateral, and dorsal regions in forebrain sections and found AQP4 immunoreactivity to emerge at E16 ventrally before lateral (E17) and dorsal (E18) areas. AQP4 staining was spread over cell processes including radial glial cells in developing cor...
International review of cell and molecular biology, 2011
Orthogonal arrays or assemblies of intramembranous particles (OAPs) are structures in the membran... more Orthogonal arrays or assemblies of intramembranous particles (OAPs) are structures in the membrane of diverse cells which were initially discovered by means of the freeze-fracturing technique. This technique, developed in the 1960s, was important for the acceptance of the fluid mosaic model of the biological membrane. OAPs were first described in liver cells, and then in parietal cells of the stomach, and most importantly, in the astrocytes of the brain. Since the discovery of the structure of OAPs and the identification of OAPs as the morphological equivalent of the water channel protein aquaporin-4 (AQP4) in the 1990s, a plethora of morphological work on OAPs in different cells was published. Now, we feel a need to balance new and old data on OAPs and AQP4 to elucidate the interrelationship of both structures and molecules. In this review, the identity of OAPs as AQP4-based structures in a diversity of cells will be described. At the same time, arguments are offered that under pat...
Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment... more Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher ...
The blood-brain barrier (BBB) does not exclusively refer to brain endothelial cells, which are th... more The blood-brain barrier (BBB) does not exclusively refer to brain endothelial cells, which are the site of the barrier proper. In the past few years, it has become increasingly clear that BBB endothelial cells depend considerably on the brain microenvironment to a degree exceeding the environmental influence in other organs. The concept of the BBB has been continuously developed over the decades, culminating now in the recognition that endothelial cell function in the brain is not limited to simply mediating energy and oxygen transfer between blood and neural tissue. Endothelial cells are rather "Janus-headed beings" that are active partners of both luminal molecules and cells, as well as subendothelial cells such as pericytes, astrocytes, and neurons. In this overview, the authors present and discuss both the role of astroglial cells in managing the BBB and aspects of pathological alterations in the brain as far as the BBB is involved. After a brief introduction of the BBB that describes the structure and function of the brain capillary endothelial cells, the authors report on both the water channel protein aquaporin-4 (AQP4) in astrocytes and the extracellular matrix between astrocytes/pericytes and endothelial cells. The AQP4 has an important impact on the homeostasis in the brain parenchyma; however, the mechanistic cascade from the composition of the astrocyte membrane to the maintenance of BBB properties in the endothelial cells, including their tight junction formation, is still completely unknown.
New treatment strategies for malignant gliomas are indispensible, due to the poor prognosis for p... more New treatment strategies for malignant gliomas are indispensible, due to the poor prognosis for patients. Fluorescence diagnosis (FD) and photodynamic therapy (PDT) are currently under intensive investigation and seem to improve the prognosis. Especially for deep seated malignant brain lesions and in order to optimize therapy new diagnostic tools are needed. In a syngeneic subcutaneous glioma mouse model we investigated the time dependent hypericin (HYP) uptake in malignant tumor tissue by microendoscopically fluorescence measurements. The HYP fluorescence in tumor was also detected by fluorescence microscopy (FM) and was compared to endoscopic data. Both methods, microendoscopy and FM, demonstrated time dependent HYP uptake in subcutaneously implanted mouse glioma. Maximum of HYP uptake was achieved after 6h, measured with both methods. FM reached a 10-fold increase in fluorescence intensity compared to the autofluorescence. Measured by microendoscopy a 2.2-fold HYP fluorescence intensity compared to the autofluorescence was detected. Microendoscopy enables visualization of small vessels even in healthy brain tissue by intravascular HYP fluorescence. The new developed microendoscope enables not only fluorescence based discrimination of tumor and healthy tissue, but also semiquantitative measurements of fluorescence intensities in vivo. Individual repetitive fluorescence diagnosis will become possible by this method and opens up new possibilities for determining optimal settings of light applications for PDT.
The aim of this article is to describe alterations of the blood-brain barrier (BBB) in gliomas. T... more The aim of this article is to describe alterations of the blood-brain barrier (BBB) in gliomas. The main clinical problem of human gliomas is the edematous swelling and the dramatic increase of intracerebral pressure, also compromising healthy areas of the brain. According to our concept, one of the main reasons on the cellular level for these clinical problems is the loss or reduction of astroglial polarity. Astroglial polarity means the specific accumulation of potassium and water channels in the superficial and perivascular astroglial endfeet membranes. The most important water channel in the CNS is the astroglial water channel protein aquaporin-4 (AQP4) which is arranged in a morphologically spectacular way, the so-called orthogonal arrays of particles (OAPs) to be observed in freeze-fracture replicas. In brain tumors, but also under conditions of trauma or inflammation, these OAPs are redistributed to membrane domains apart from endfeet areas. Probably, this dislocation might be due to the degradation of the proteoglycan agrin by the matrix metalloproteinase 3 (MMP3). Agrin binds to the dystrophin-dystroglycan-complex (DDC), which in turn is connected to AQP4. As a consequence, agrin loss may lead to a redistribution of AQP4 and a compromised directionality of water transport out of the cell, finally to cytotoxic edema. This in turn is hypothesized to lead to a breakdown of the BBB characterized by disturbed tight junctions, and thus to the development of vasogenic edema. However, the mechanism how the loss of polarity is related to the disturbance of microvascular tight junctions is completely unknown so far.
In this paper, a rare case of subependymoma of the fourth ventricle in identical female twins is ... more In this paper, a rare case of subependymoma of the fourth ventricle in identical female twins is reported. Magnetic resonance imaging and CT showed nearly identical locations of the tumors in the fourth ventricle and similar growth patterns of the tumors in both sisters. Likewise, postoperative histopathological analysis of both tumors revealed the typical histological appearance of subependymomas. Subependymoma is a rare, low-grade glioma of the CNS, slowly growing and usually asymptomatic. If symptomatic, a subependymoma can in some cases lead to sudden death caused by pressure on the brainstem or decompensated secondary hydrocephalus. This case demonstrates the importance of detecting tumors early and thereby preventing symptoms arising from increasing intracranial pressure, and optimizing therapy options.
Antiepileptic treatment of brain tumor patients mainly depends on the individual physician's ... more Antiepileptic treatment of brain tumor patients mainly depends on the individual physician's choice rather than on well-defined predictive factors. We investigated the predictive value of defined clinical parameters to formulate a model of risk estimations for subpopulations of brain tumor patients. We enclosed 650 patients > 18 years of age who underwent brain tumor surgery and included a number of clinical data. Logistic regressions were performed to determine the effect sizes of seizure-related risk factors and to develop prognostic scores for the occurrence of preoperative and early postoperative seizures. A total of 492 patients (334 gliomas) were eligible for logistic regression for preoperative seizures, and 338 patients for early postoperative seizures. Age ≤ 60 years (odds ratio [OR] = 1.66, p = 0.020), grades I and II glioma (OR = 4.00, p = 0.0002), total tumor/edema volume ≤ 64cm(3) (OR = 2.18, p = 0.0003), and frontal location (OR = 2.28, p = 0.034) demonstrated a...
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 18, 2015
To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour sp... more To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14-0.24) to 3.26 (95% CI: 4.13-2.62) for chondrosarcomas (radioresistant) and classical seminomas ...
Tumour resection in the Rolandic region is a challenge. Aim of this study is to review a series o... more Tumour resection in the Rolandic region is a challenge. Aim of this study is to review a series of patients malignant glioma surgery in the Rolandic region which was performed by combinations of neuronavigation, sonography, 5-aminolevulinic acid fluorescence guided (5-ALA) surgery and intraoperative electrophysiological monitoring (IOM). 29 patients suffering malignant gliomas in the motor cortex (17) and sensory cortex (12) were analyzed with respect to functional outcome and grade of resections. Improvement of motor function was seen in 41.5% one week after surgery, 41.5% were stable, only 17% deteriorated. After three months patients had an improvement of motor function in 56%, of Karnofsky Score (KPS) 27% and sensory function was improved in 8%. Deterioration of motor function was seen in 16%, in sensory function 4% and in KPS 28% after three months. 25% showed no residual tumour in early post surgical contrast enhanced MRI. 10% had less than 2% residual tumour and 15% had 2-5% residual tumour. Preoperative functional neuroimaging, neuronavigation for planning the surgical approach and resection margins, intraoperative sonography and 5-ALA guided surgery in combination with the application of IOM shows that functional outcome and total to subtotal resection of malignant glioma in the Rolandic region is feasible.
We analyzed aquaporin 4 and -1 expression in subependymomas, benign and slow growing brain tumors... more We analyzed aquaporin 4 and -1 expression in subependymomas, benign and slow growing brain tumors WHO grade I. Ten subependymoma cases were investigated, five of the fossa inferior and five of the fossa superior. Using immunohistochemistry, we observed different aquaporin expression patterns depending on localization: aquaporin 4 and -1 were detected in infratentorial subependymomas in the entire tumor tissue. In contrast, supratentorial subependymomas revealed aquaporin 4 and -1 expression only in border areas of the tumor. PCR analyses however showed no difference in aquaporin 4 expression between all subependymomas independent of localization but at higher levels than in normal brain. In contrast, aquaporin 1 RNA levels were found to be higher only in infratentorial samples compared to supratentorial and normal brain samples. The reason for the different distribution pattern of aquaporin 4 in subependymomas still remains unclear. On the cellular level, aquaporin 4 was redistributed on the surface of the tumor cells, and in freeze fracture replicas no orthogonal arrays of particles were found. This was similar to our previous findings in malignant glioblastomas. From these studies, we know that extracellular matrix molecules within the tumor like agrin and its receptor alpha-dystroglycan are involved in forming orthogonal arrays of particles. In subependymomas neither agrin nor alpha-dystroglycan were detected around blood vessels. Taken together, we show in this study that in the benign subependymomas aquaporins 1 and 4 are dramatically redistributed and upregulated. We speculate that extracellular environments of infra- and supratentorial subependymomas are different and lead to different distribution patterns of aquaporin 4 and -1.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, Jan 9, 2015
To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex viv... more To establish a clinically applicable protocol for quantification of residual γH2AX foci in ex vivo irradiated tumour samples and to apply this method in a proof-of-concept feasibility study to patient-derived tumour specimens. Evaluation of γH2AX foci formation and disappearance in excised FaDu tumour specimens after (a) different incubation times in culture medium, 4Gy irradiation and fixation after 24h (cell recovery), (b) 10h medium incubation, 4Gy irradiation and fixation after various time points (double strand break repair kinetics), and (c) 10h medium incubation, irradiation with graded single radiation doses and fixation after 24h (dose-response). The optimised protocol was applied to patient-derived samples of seminoma, prostate cancer and glioblastoma multiforme. Post excision or biopsy, tumour tissues showed stable radiation-induced γH2AX foci values in oxic cells after >6h of recovery in medium. Kinetics of foci disappearance indicated a plateau of residual foci after...
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience, 2014
The main water channel in the brain, aquaporin-4 (AQP4) is involved in maintaining homeostasis an... more The main water channel in the brain, aquaporin-4 (AQP4) is involved in maintaining homeostasis and water exchange in the brain. In adult mammalian brains, it is expressed in astrocytes, mainly, and in high densities in the membranes of perivascular and subpial endfeet. Here, we addressed the question how this polarized expression is established during development. We used immunocytochemistry against AQP4, zonula occludens protein-1, glial fibrillary acidic protein, and β-dystroglycan to follow astrocyte development in E15 to P3 NMRI mouse brains, and expression of AQP4. In addition we used freeze-fracture electron microscopy to detect AQP4 in the form of orthogonal arrays of particles (OAPs) on the ultrastructural level. We analyzed ventral, lateral, and dorsal regions in forebrain sections and found AQP4 immunoreactivity to emerge at E16 ventrally before lateral (E17) and dorsal (E18) areas. AQP4 staining was spread over cell processes including radial glial cells in developing cor...
International review of cell and molecular biology, 2011
Orthogonal arrays or assemblies of intramembranous particles (OAPs) are structures in the membran... more Orthogonal arrays or assemblies of intramembranous particles (OAPs) are structures in the membrane of diverse cells which were initially discovered by means of the freeze-fracturing technique. This technique, developed in the 1960s, was important for the acceptance of the fluid mosaic model of the biological membrane. OAPs were first described in liver cells, and then in parietal cells of the stomach, and most importantly, in the astrocytes of the brain. Since the discovery of the structure of OAPs and the identification of OAPs as the morphological equivalent of the water channel protein aquaporin-4 (AQP4) in the 1990s, a plethora of morphological work on OAPs in different cells was published. Now, we feel a need to balance new and old data on OAPs and AQP4 to elucidate the interrelationship of both structures and molecules. In this review, the identity of OAPs as AQP4-based structures in a diversity of cells will be described. At the same time, arguments are offered that under pat...
Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment... more Malignant gliomas are diffuse infiltrative growing tumors with a poor prognosis despite treatment with a combination of surgery, radiotherapy and chemotherapy. It has been shown recently that complete tumor resection improves the survival time significantly. Hypericin, a component of St. Johns Wort, is one of the most powerful photosensitizers in nature. The aim of the present study was to investigate accumulation of hypericin in intracerebral implanted malignant glioma in vivo. Rats underwent stereotactic implantation of C6 glioma cells. After intravenous administration of hypericin (5 mg per kg body weight), accumulation of the compound was studied in tumor, the infiltration zone surrounding the tumor and healthy brain (contralateral hemisphere) by fluorescence microscopy between 0 and 48 h after injection. Results were compared by one-way analysis of variance. For post hoc pair-wise comparison the Tukey-Kramer HSD test was used. Accumulation of hypericin was significantly higher ...
The blood-brain barrier (BBB) does not exclusively refer to brain endothelial cells, which are th... more The blood-brain barrier (BBB) does not exclusively refer to brain endothelial cells, which are the site of the barrier proper. In the past few years, it has become increasingly clear that BBB endothelial cells depend considerably on the brain microenvironment to a degree exceeding the environmental influence in other organs. The concept of the BBB has been continuously developed over the decades, culminating now in the recognition that endothelial cell function in the brain is not limited to simply mediating energy and oxygen transfer between blood and neural tissue. Endothelial cells are rather "Janus-headed beings" that are active partners of both luminal molecules and cells, as well as subendothelial cells such as pericytes, astrocytes, and neurons. In this overview, the authors present and discuss both the role of astroglial cells in managing the BBB and aspects of pathological alterations in the brain as far as the BBB is involved. After a brief introduction of the BBB that describes the structure and function of the brain capillary endothelial cells, the authors report on both the water channel protein aquaporin-4 (AQP4) in astrocytes and the extracellular matrix between astrocytes/pericytes and endothelial cells. The AQP4 has an important impact on the homeostasis in the brain parenchyma; however, the mechanistic cascade from the composition of the astrocyte membrane to the maintenance of BBB properties in the endothelial cells, including their tight junction formation, is still completely unknown.
New treatment strategies for malignant gliomas are indispensible, due to the poor prognosis for p... more New treatment strategies for malignant gliomas are indispensible, due to the poor prognosis for patients. Fluorescence diagnosis (FD) and photodynamic therapy (PDT) are currently under intensive investigation and seem to improve the prognosis. Especially for deep seated malignant brain lesions and in order to optimize therapy new diagnostic tools are needed. In a syngeneic subcutaneous glioma mouse model we investigated the time dependent hypericin (HYP) uptake in malignant tumor tissue by microendoscopically fluorescence measurements. The HYP fluorescence in tumor was also detected by fluorescence microscopy (FM) and was compared to endoscopic data. Both methods, microendoscopy and FM, demonstrated time dependent HYP uptake in subcutaneously implanted mouse glioma. Maximum of HYP uptake was achieved after 6h, measured with both methods. FM reached a 10-fold increase in fluorescence intensity compared to the autofluorescence. Measured by microendoscopy a 2.2-fold HYP fluorescence intensity compared to the autofluorescence was detected. Microendoscopy enables visualization of small vessels even in healthy brain tissue by intravascular HYP fluorescence. The new developed microendoscope enables not only fluorescence based discrimination of tumor and healthy tissue, but also semiquantitative measurements of fluorescence intensities in vivo. Individual repetitive fluorescence diagnosis will become possible by this method and opens up new possibilities for determining optimal settings of light applications for PDT.
The aim of this article is to describe alterations of the blood-brain barrier (BBB) in gliomas. T... more The aim of this article is to describe alterations of the blood-brain barrier (BBB) in gliomas. The main clinical problem of human gliomas is the edematous swelling and the dramatic increase of intracerebral pressure, also compromising healthy areas of the brain. According to our concept, one of the main reasons on the cellular level for these clinical problems is the loss or reduction of astroglial polarity. Astroglial polarity means the specific accumulation of potassium and water channels in the superficial and perivascular astroglial endfeet membranes. The most important water channel in the CNS is the astroglial water channel protein aquaporin-4 (AQP4) which is arranged in a morphologically spectacular way, the so-called orthogonal arrays of particles (OAPs) to be observed in freeze-fracture replicas. In brain tumors, but also under conditions of trauma or inflammation, these OAPs are redistributed to membrane domains apart from endfeet areas. Probably, this dislocation might be due to the degradation of the proteoglycan agrin by the matrix metalloproteinase 3 (MMP3). Agrin binds to the dystrophin-dystroglycan-complex (DDC), which in turn is connected to AQP4. As a consequence, agrin loss may lead to a redistribution of AQP4 and a compromised directionality of water transport out of the cell, finally to cytotoxic edema. This in turn is hypothesized to lead to a breakdown of the BBB characterized by disturbed tight junctions, and thus to the development of vasogenic edema. However, the mechanism how the loss of polarity is related to the disturbance of microvascular tight junctions is completely unknown so far.
In this paper, a rare case of subependymoma of the fourth ventricle in identical female twins is ... more In this paper, a rare case of subependymoma of the fourth ventricle in identical female twins is reported. Magnetic resonance imaging and CT showed nearly identical locations of the tumors in the fourth ventricle and similar growth patterns of the tumors in both sisters. Likewise, postoperative histopathological analysis of both tumors revealed the typical histological appearance of subependymomas. Subependymoma is a rare, low-grade glioma of the CNS, slowly growing and usually asymptomatic. If symptomatic, a subependymoma can in some cases lead to sudden death caused by pressure on the brainstem or decompensated secondary hydrocephalus. This case demonstrates the importance of detecting tumors early and thereby preventing symptoms arising from increasing intracranial pressure, and optimizing therapy options.
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Papers by Susan Noell