Tabotamp®, Respectively, Surgicel®, Increases the Cell Death of Neuronal and Glial Cells In Vitro

Oxidized regenerated cellulose (ORC) is an approved absorbable hemostat in neurosurgery, and contains 18–21% carboxylic acid groups. This modification leads to a low pH in aqueous solutions. Therefore, the aim of study was to analyze the pH-dependent effects of the ORC Tabotamp® on astrocytes, Schwann cells, and neuronal cells in vitro to investigate whether Tabotamp® is a suitable hemostat in cerebral eloquent areas. The ORC-dependent pH value changes were measured with (i) a pH meter, (ii) electron paramagnetic resonance spectroscopy, using pH-sensitive spin probes, and (iii) with fluorescence microscopy. Cell lines from neurons, astrocytes, and Schwann cells, as well as primary astrocytes were incubated with increasing areas of Tabotamp®. Cytotoxicity was detected using a fluorescence labeled DNA-binding dye. In addition, the wounding extent was analyzed via crystal violet staining of cell layers. The strongest pH reduction (to 2.2) was shown in phosphate buffered saline, whereas culture medium and cerebrospinal fluid demonstrated a higher buffer capacity during Tabotamp® incubation. In addition, we could detect a distance-dependent pH gradient by fluorescence microscopy. Incubation of Tabotamp® on cell monolayers led to detachment of covered cells and showed increased cytotoxicity in all tested cell lines and primary cells depending on the covered area. These in vitro results indicate that Tabotamp® may not be a suitable hemostat in cerebral eloquent areas

Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Nimodipine is well characterized for the management of SAH (subarachnoid hemorrhage) and has been shown to promote a better outcome and less DIND (delayed ischemic neurological deficits). In rat experiments, enhanced axonal sprouting and higher survival of motoneurons was demonstrated after cutting or crushing the facial nerve by nimodipine. These results were confirmed in clinical trials following vestibular Schwannoma surgery. The mechanism of the protective competence of nimodipine is unknown. Therefore, in this study, we established an in vitro model to examine the survival of Neuro2a cells after different stress stimuli occurring during surgery with or without nimodipine. Nimodipine significantly decreased ethanol-induced cell death of cells up to approximately 9% in all tested concentrations. Heat-induced cell death was diminished by approximately 2.5% by nimodipine. Cell death induced by mechanical treatment was reduced up to 15% by nimodipine. Our findings indicate that nimodipine rescues Neuro2a cells faintly, but significantly, from ethanol-, heat- and mechanically-induced cell death to different extents in a dosage-dependent manner. This model seems suitable for further investigation of the molecular mechanisms involved in the neuroprotective signal pathways influenced by nimodipine

Makroskopische und mikroskopische Veränderungen des N. vestibulocochlearis nach Gamma-Knife-Therapie

We report on a case in which macroscopic and microscopic changes of the vestibulocochlear nerve could be observed after radiosurgery of an intrameatal vestibular schwannoma. This case shows for the first time a morphological correlate for undesirable effects after radiosurgical treatment of a vestibular schwannoma and indicates that despite a certain distance to the actual tumor, degenerative changes in neural structures can be expected

Insufficient Closing Forces of Yasargil Titanium Clips in Two Small Aneurysms Detected with Intraoperative Indocyanine Green Videoangiography

Background and Study Aims Aneurysm clips must have adequate closing forces because residual blood flow in clipped aneurysms may result in aneurysm recurrence. Such flow can be intraoperatively detected by visual inspection, microvascular Doppler sonography, indocyanine green videoangiography (ICG-V), angiography, and puncture. Patients We present two patients with ruptured very small middle cerebral artery aneurysms (3 and 2.9 mm). The necks of both aneurysms were microsurgically clipped with Yasargil aneurysm clips without any complications. Results In both aneurysms, visual inspection suggested complete occlusion, but ICG-V showed persistent residual blood flow between the middle parts of the clip blades. The first patient was treated with a 5.4-mm FT744T clip (closing force of 1.47 N). After the ICG-V finding, a second 3.9-mm FT714T clip (closing force of 1.08 N) was placed on the tips of the already implanted clip to increase the closing forces. Subsequent ICG-V did not show any further residual blood flow. In the second patient, the aneurysm was clipped with an 8.0-mm FE764K clip (closing force of 1.77 N). Intraoperative ICG-V showed persistent residual blood flow within the aneurysmal dome despite complete closure of the clip. The clip was repositioned closer to the parent vessel. Consecutive ICG-V did not show any residual blood flow. Conclusion Visually undetected incomplete aneurysm occlusion can be revealed with ICG-V. In very small aneurysms, standard closing forces of clips may not be sufficient and complete closure of the clip branches should be intraoperatively validated with ICG-V

Variants of Oxidized Regenerated Cellulose and Their Distinct Effects on Neuronal Tissue

Based on oxidized regenerated cellulose (ORC), several hemostyptic materials, such as Tabotamp®, Equicel® and Equitamp®, have been developed to approach challenging hemostasis in neurosurgery. The present study compares ORC that differ in terms of compositions and properties, regarding their structure, solubility, pH values and effects on neuronal tissue. Cytotoxicity was detected via DNA-binding fluorescence dye in Schwann cells, astrocytes, and neuronal cells. Additionally, organotypic hippocampal slice cultures (OHSC) were analyzed, using propidium iodide, hematoxylin-eosin, and isolectin B4 staining to investigate the cellular damage, cytoarchitecture, and microglia activation. Whereas Equicel® led to a neutral pH, Tabotamp® (pH 2.8) and Equitamp® (pH 4.8) caused a significant reduction of pH (p < 0.001). Equicel® and Tabotamp® increased cytotoxicity significantly in several cell lines (p < 0.01). On OHSC, Tabotamp® and Equicel® led to a stronger and deeper damage to the neuronal tissue than Equitamp® or gauze (p < 0.01). Equicel® increased strongly the number of microglia cells after 24 h (p < 0.001). Microglia cells were not detectable after Tabotamp® treatment, presumably due to an artifact caused by strong pH reduction. In summary, our data imply the use of Equicel®, Tabotamp® or Equitamp® for specific applications in distinct clinical settings depending on their localization or tissue properties

MSI1 Promotes the Expression of the GBM Stem Cell Marker CD44 by Impairing miRNA-Dependent Degradation

The stem cell marker Musashi1 (MSI1) is highly expressed during neurogenesis and in glioblastoma (GBM). MSI1 promotes self-renewal and impairs differentiation in cancer and non-malignant progenitor cells. However, a comprehensive understanding of its role in promoting GBM-driving networks remains to be deciphered. We demonstrate that MSI1 is highly expressed in GBM recurrences, an oncologist’s major defiance. For the first time, we provide evidence that MSI1 promotes the expression of stem cell markers like CD44, co-expressed with MSI1 within recurrence-promoting cells at the migrating front of primary GBM samples. With GBM cell models of pediatric and adult origin, including isolated primary tumorspheres, we show that MSI1 promotes stem cell-like characteristics. Importantly, it impairs CD44 downregulation in a 3′UTR- and miRNA-dependent manner by controlling mRNA turnover. This regulation is disturbed by the previously reported MSI1 inhibitor luteolin, providing further evidence for a therapeutic target potential of MSI1 in GBM treatment

Vestibular Schwannoma Volume and Tumor Growth Correlates with Macrophage Marker Expression

Vestibular schwannoma is the most common benign tumor of the cerebellopontine angle and originates from Schwann cells surrounding the vestibulocochlear nerve. Since the size of the VS varies widely, affected patients suffer from symptoms of varying severity. It is often difficult to determine the optimal time for therapy, due to the unpredictability of the growth rate. Despite many investigations on influencing factors, no mechanism responsible for the increase in the growth rate of certain VS has been identified so far. Therefore, the present study investigates the influence of the seven markers: Ki-67, cyclooxygenase 2 (COX2), vascular endothelial growth factor (VEGF), macrophage colony-stimulating factor (M-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), CD163, and CD68 on tumor progression and tumor size in a cohort of 173 VS. The markers were determined by quantitative PCR and correlated with tumor volume and VS growth rate. The analysis showed a significantly negative correlation of the Ki-67, COX2, and VEGF on tumor volume. Moreover, with a higher volume of VS, the expression of the macrophage markers CD68, CD163, and GM-CSF increased significantly. Our results suggest that the increase in VS size is not primarily due to Schwann cell growth but to an infiltration of macrophages. This may have an impact on non-invasive therapy to preserve the hearing function of affected patients