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Article ; Online: Nimodipine Treatment Protects Auditory Hair Cells from Cisplatin-Induced Cell Death Accompanied by Upregulation of LMO4

Saskia Fritzsche / Christian Strauss / Christian Scheller / Sandra Leisz

International Journal of Molecular Sciences, Vol 23, Iss 5780, p

2022 Volume 5780

Abstract: Ototoxicity is one of the main dose-limiting side effects of cisplatin chemotherapy and impairs the quality of life of tumor patients dramatically. Since there is currently no established standard therapy targeting hearing loss in cisplatin treatment, ... ...

Abstract	Ototoxicity is one of the main dose-limiting side effects of cisplatin chemotherapy and impairs the quality of life of tumor patients dramatically. Since there is currently no established standard therapy targeting hearing loss in cisplatin treatment, the aim of this study was to investigate the effect of nimodipine and its role in cell survival in cisplatin-associated hearing cell damage. To determine the cytotoxic effect, the cell death rate was measured using undifferentiated and differentiated UB/OC−1 and UB/OC−2 cells, after nimodipine pre-treatment and stress induction by cisplatin. Furthermore, immunoblot analysis and intracellular calcium measurement were performed to investigate anti-apoptotic signaling, which was associated with a reduced cytotoxic effect after nimodipine pre-treatment. Cisplatin’s cytotoxic effect was significantly attenuated by nimodipine up to 61%. In addition, nimodipine pre-treatment counteracted the reduction in LIM Domain Only 4 (LMO4) by cisplatin, which was associated with increased activation of Ak strain transforming/protein kinase B (Akt), cAMP response element-binding protein (CREB), and signal transducers and activators of transcription 3 (Stat3). Thus, nimodipine presents a potentially well-tolerated substance against the ototoxicity of cisplatin, which could result in a significant improvement in patients’ quality of life.
Keywords	nimodipine ; cisplatin ; ototoxicity ; otoprotection ; hearing ; auditory hair cells ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Optimized preoperative determination of nerve of origin in patients with vestibular schwannoma

Torsten Rahne / Stefan K. Plontke / Laura Fröhlich / Christian Strauss

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 10

Abstract: Abstract In vestibular schwannoma (VS) patients hearing outcome and surgery related risks can vary and depend on the nerve of origin. Preoperative origin differentiation between inferior or superior vestibular nerve may influence the decision on ... ...

Abstract	Abstract In vestibular schwannoma (VS) patients hearing outcome and surgery related risks can vary and depend on the nerve of origin. Preoperative origin differentiation between inferior or superior vestibular nerve may influence the decision on treatment, and the selection of optimal treatment and counselling modalities. A novel scoring system based on functional tests was designed to predict the nerve of origin for VS and was applied to a large number of consecutive patients. A prospective, double blind, cohort study including 93 patients with suspected unilateral VS was conducted at a tertiary referral centre. Preoperatively before tumor resection a functional test battery [video head-impulse test (vHIT) of all semicircular canals (SCC)], air-conducted cervical/ocular vestibular evoked myogenic potential tests (cVEMP, oVEMP), pure-tone audiometry, and speech discrimination was applied. Sensitivity and specificity of prediction of intraoperative finding by a preoperative score based on vHIT gain, cVEMP and oVEMP amplitudes and asymmetry ratios was calculated. For the prediction of inferior vestibular nerve origin, sensitivity was 73% and specificity was 80%. For the prediction of superior vestibular nerve origin, sensitivity was 60% and specificity was 90%. Based on the trade-off between sensitivity and specificity, optimized cut-off values of − 0.32 for cVEMP and − 0.11 for oVEMP asymmetry ratios and vHIT gain thresholds of 0.77 (anterior SCC), 0.84 (lateral SCC) and 0.80 (posterior SCC) were identified by receiver operator characteristic curves. The scoring system based on preoperative functional tests improves prediction of nerve of origin and can be applied in clinical routine.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Glycation Interferes with the Expression of Sialyltransferases in Meningiomas

Philipp Selke / Kaya Bork / Tao Zhang / Manfred Wuhrer / Christian Strauss / Rüdiger Horstkorte / Maximilian Scheer

Cells, Vol 10, Iss 3298, p

2021 Volume 3298

Abstract: Meningiomas are the most common non-malignant intracranial tumors and prefer, like most tumors, anaerobic glycolysis for energy production (Warburg effect). This anaerobic glycolysis leads to an increased synthesis of the metabolite methylglyoxal (MGO) ... ...

Abstract	Meningiomas are the most common non-malignant intracranial tumors and prefer, like most tumors, anaerobic glycolysis for energy production (Warburg effect). This anaerobic glycolysis leads to an increased synthesis of the metabolite methylglyoxal (MGO) or glyoxal (GO), which is known to react with amino groups of proteins. This reaction is called glycation, thereby building advanced glycation end products (AGEs). In this study, we investigated the influence of glycation on sialylation in two meningioma cell lines, representing the WHO grade I (BEN-MEN-1) and the WHO grade III (IOMM-Lee). In the benign meningioma cell line, glycation led to differences in expression of sialyltransferases ( ST3GAL1/2/3/5/6, ST6GAL1/2, ST6GALNAC2/6 , and ST8SIA1/2 ), which are known to play a role in tumor progression. We could show that glycation of BEN-MEN-1 cells led to decreased expression of ST3Gal5. This resulted in decreased synthesis of the ganglioside GM3, the product of ST3Gal5. In the malignant meningioma cell line, we observed changes in expression of sialyltransferases ( ST3GAL1/2/3, ST6GALNAC5 , and ST8SIA1 ) after glycation, which correlates with less aggressive behavior.
Keywords	intracranial tumor ; methylglyoxal ; MGO ; sialylation ; tumorigenesis ; posttranslational modification ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nimodipine Exerts Time-Dependent Neuroprotective Effect after Excitotoxical Damage in Organotypic Slice Cultures

Urszula Hohmann / Chalid Ghadban / Tim Hohmann / Joshua Kleine / Miriam Schmidt / Christian Scheller / Christian Strauss / Faramarz Dehghani

International Journal of Molecular Sciences, Vol 23, Iss 3331, p

2022 Volume 3331

Abstract: During injuries in the central nervous system, intrinsic protective processes become activated. However, cellular reactions, especially those of glia cells, are frequently unsatisfactory, and further exogenous protective mechanisms are necessary. ... ...

Abstract	During injuries in the central nervous system, intrinsic protective processes become activated. However, cellular reactions, especially those of glia cells, are frequently unsatisfactory, and further exogenous protective mechanisms are necessary. Nimodipine, a lipophilic L-type calcium channel blocking agent is clinically used in the treatment of aneurysmal subarachnoid haemorrhage with neuroprotective effects in different models. Direct effects of nimodipine on neurons amongst others were observed in the hippocampus as well as its influence on both microglia and astrocytes. Earlier studies proposed that nimodipine protective actions occur not only via calcium channel-mediated vasodilatation but also via further time-dependent mechanisms. In this study, the effect of nimodipine application was investigated in different time frames on neuronal damage in excitotoxically lesioned organotypic hippocampal slice cultures. Nimodipine, but not nifedipine if pre-incubated for 4 h or co-applied with NMDA, was protective, indicating time dependency. Since blood vessels play no significant role in our model, intrinsic brain cell-dependent mechanisms seems to strongly be involved. We also examined the effect of nimodipine and nifedipine on microglia survival. Nimodipine seem to be a promising agent to reduce secondary damage and reduce excitotoxic damage.
Keywords	nimodipine ; excitotoxicity ; nifedipine ; neuroprotection ; microglia ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610
Language	English
Publishing date	2022-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Nimodipine but Not Nifedipine Promotes Expression of Fatty Acid 2-Hydroxylase in a Surgical Stress Model Based on Neuro2a Cells

Eva Herzfeld / Lea Speh / Christian Strauss / Christian Scheller

International Journal of Molecular Sciences, Vol 18, Iss 5, p

2017 Volume 964

Abstract: Nimodipine is well characterized for the management of aneurysmal subarachnoid hemorrhage and has been shown to promote a better outcome and less delayed ischemic neurological deficits. Animal and clinical trials show neuroprotective efficacy following ... ...

Abstract	Nimodipine is well characterized for the management of aneurysmal subarachnoid hemorrhage and has been shown to promote a better outcome and less delayed ischemic neurological deficits. Animal and clinical trials show neuroprotective efficacy following nerve injuries. We showed a neuroprotective effect on Neuro2a cells. Subsequent microarray analysis revealed—among others—fatty acid 2-hydroxylase (FA2H) upregulated by nimodipine in vitro, which is a component of myelin synthesis. Differentiated Neuro2a cells were analyzed for nimodipine-mediated survival considering stress treatment in comparison to nifedipine-treatment. Cell survival was determined by measurement of LDH activity in the culture medium. Nimodipine decreased surgery-like stress-induced cell death of differentiated Neuro2a cells. Neuro2a cell culture was analyzed for changes in FA2H expression induced by nimodipine or nifedipine in surgery-like stress conditions. We analyzed expression levels of FA2H mRNA and protein by qPCR using fa2h specific primers or a FA2H-specific antibody in nimodipine or nifedipine non- and pre-treated Neuro2a cell culture, respectively. Nimodipine but not nifedipine increases FA2H protein levels and also significantly increases mRNA levels of FA2H in both undifferentiated and differentiated Neuro2a cells. Our findings indicate that higher expression of FA2H induced by nimodipine may cause higher survival of Neuro2a cells stressed with surgery-like stressors.
Keywords	nimodipine ; nifedipine ; neuroprotection ; Neuro2a ; stress ; FA2H ; myelin ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2017-05-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Variants of Oxidized Regenerated Cellulose and Their Distinct Effects on Neuronal Tissue

Joshua Kleine / Sandra Leisz / Chalid Ghadban / Tim Hohmann / Julian Prell / Christian Scheller / Christian Strauss / Sebastian Simmermacher / Faramarz Dehghani

International Journal of Molecular Sciences, Vol 22, Iss 11467, p

2021 Volume 11467

Abstract: 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 ... ...

Abstract	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 B 4 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.
Keywords	cellulose applications ; oxidized regenerated cellulose ; Tabotamp ® ; Equicel ® ; Equitamp ® ; cell death ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Prophylactic nimodipine treatment for hearing preservation after vestibular schwannoma surgery

Christian Scheller / Christian Strauss / Sandra Leisz / Pia Hänel / Ariane Klemm / Simone Kowoll / Iris Böselt / Torsten Rahne / Andreas Wienke

Trials, Vol 22, Iss 1, Pp 1-

study protocol of a randomized multi-center phase III trial—AkniPro 2

2021 Volume 10

Abstract: Abstract Background A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, ... ...

Abstract	Abstract Background A previously performed phase III trial on 112 subjects investigating prophylactic nimodipine treatment in vestibular schwannoma (VS) surgery showed no clear beneficial effects on preservation of facial and cochlear nerve functions, though it should be considered that protection of facial nerve function was the primary outcome. However, the risk for postoperative hearing loss was halved in the nimodipine group compared to the control group (OR 0.49; 95% CI 0.18–1.30; p = 0.15). Accordingly, this phase III extension trial investigates the efficacy and safety of prophylactic nimodipine for hearing preservation in VS surgery. Methods This is a randomized, multi-center, two-armed, open-label phase III trial with blinded expert review and two-stage with interim analysis. Three hundred thirty-six adults with the indication for microsurgical removal of VS (Koos I–IV) and serviceable preoperative hearing (Gardner-Robertson scale (GR) 1–3) are assigned to either the therapy (intravenous nimodipine 1–2 mg/h from the day before surgery until the fifth postoperative day and standard of care) or the control group (surgery only and standard of care). The primary endpoint of the trial is postoperative cochlear nerve function measured before discharge according to GR 1–3 versus GR 4–5 (binary). Hearing function will be determined by pre- and postoperative audiometry with speech discrimination, which will be evaluated by a blinded expert reviewer. Furthermore, patient-reported outcomes using standardized questionnaires will be analyzed. Discussion Prophylactic parenteral nimodipine treatment may have a positive effect on hearing preservation in VS surgery and would improve patient’s quality of life. Further secondary analyses are planned. Except for dose-depending hypotension, nimodipine is known as a safe drug. In the future, prophylactic nimodipine treatment may be recommended as a routine medication in VS surgery. VS can be considered as an ideal model for clinical evaluation of neuroprotection, since ...
Keywords	Nimodipine ; Hearing preservation ; Vestibular schwannoma ; Acoustic neuroma ; Medicine (General) ; R5-920
Subject code	610
Language	English
Publishing date	2021-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Production of neutralizing antibodies against the secreted Clostridium chauvoei toxin A (CctA) upon blackleg vaccination

Nicholson, Pamela / Julia Furrer / Michael Hässig / Christian Strauss / Manfred Heller / Sophie Braga-Lagache / Joachim Frey

Anaerobe. 2019 Apr., v. 56

2019

Abstract: Clostridium chauvoei is the etiologic agent of blackleg in cattle, inducing fever, severe myonecrosis, oedemic lesions and ultimately death of infected animals. The pathogen often results in such rapid death that antibiotic therapy is futile and thus ... ...

Abstract	Clostridium chauvoei is the etiologic agent of blackleg in cattle, inducing fever, severe myonecrosis, oedemic lesions and ultimately death of infected animals. The pathogen often results in such rapid death that antibiotic therapy is futile and thus vaccination is the only efficient strategy in order to control the disease. The β-barrel pore forming leucocidin Clostridium chauvoei toxin A (CctA) is one of the best characterised toxins of C. chauvoei and has been shown to be an important virulence factor. It has been reported to induce protective immunity and is conserved across C. chauvoei strains collected from diverse geographical locations for more than 50 years. The aim of this study was to identify the location of the CctA toxin during liquid culture fermentation and to use CctA to develop an in vitro assay to replace the current guinea pig challenge assay for vaccine potency in standard batch release procedures. We report that CctA is fully secreted in C. chauvoei culture and show that it is found abundantly in the supernatant of liquid cultures. Sera from cattle vaccinated with a commercial blackleg vaccine revealed strong haemolysin-neutralizing activity against recombinant CctA which reached titres of 1000 times 28 days post-vaccination. Similarly, guinea pig sera from an official potency control test reached titres of 600 times 14 days post-vaccination. In contrast, ELISA was not able to specifically measure anti-CctA antibodies in cattle serum due to strong cross-reactions with antibodies against other proteins present pre-vaccination. We conclude that haemolysin-neutralizing antibodies are a valuable measurement for protective immunity against blackleg and have the potential to be a suitable replacement of the guinea pig challenge potency test, which would forego the unnecessary challenge of laboratory animals.
Keywords	Clostridium chauvoei ; Geographical Locations ; animal use replacement ; antibiotics ; blood serum ; cattle ; death ; disease control ; enzyme-linked immunosorbent assay ; fever ; guinea pigs ; immunity ; in vitro studies ; laboratory animals ; liquid state fermentation ; liquids ; neutralizing antibodies ; pathogens ; proteins ; toxins ; vaccination ; vaccines ; virulence
Language	English
Dates of publication	2019-04
Size	p. 78-87.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	1237621-8
ISSN	1075-9964
ISSN	1075-9964
DOI	10.1016/j.anaerobe.2019.02.011
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Landnutzungswandel durch demographischen Wandel? Evidenzen und Schlussfolgerungen

Jens Hoffmann / Peter Dehne / Thomas Weith / Christian Strauß / Nadin Gaasch M.A.

Raumforschung und Raumordnung, Vol 73, Iss

2015 Volume 2

Abstract: Demographic change is often mentioned as one main driver for land use change. Since the 1970s, experts of spatial planning discuss consequences of demographic change. Currently, the topic is of importance in societal debates, too. However, does ... ...

Abstract	Demographic change is often mentioned as one main driver for land use change. Since the 1970s, experts of spatial planning discuss consequences of demographic change. Currently, the topic is of importance in societal debates, too. However, does demographic change really directly influence land use change? As yet, comprehensive models of land use change are missing that describe the consequences of demographic change on land use in par- ticular; mainly partial models exist up to now. Thus, this paper contributes to the questions if there is any empirical evidence for direct relations between demographic change and land use change and what consequences this has for spatial research and spatial development policies. For an- swering these questions, we conducted a comprehensive literature analysis for the period from 2005 to 2013 with regard to the German discourse and discussed the results at two expert workshops. The analysis shows a lack of refer- ences that provide evidence for a direct influence of demo- graphic change on land use. This is in particular significant for the following types of land use: agriculture, forestry, tourism, and nature protection. Also indirect cause effect relations cannot be proved fully due to the lack of empiri- cism. Consequently, serious uncertainties exist regarding the effectiveness of spatial planning and spatial develop- ment approaches within this context.
Keywords	Demographic change ; Land use ; Land use change ; Land management ; Cities. Urban geography ; GF125 ; Urbanization. City and country ; HT361-384
Subject code	710 ; 910
Language	German
Publishing date	2015-04-01T00:00:00Z
Publisher	oekom verlag GmbH
Document type	Article ; Online
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Article ; Online: Investigation of the Neuroprotective Impact of Nimodipine on Neuro2a Cells by Means of a Surgery-Like Stress Model

Eva Herzfeld / Christian Strauss / Sebastian Simmermacher / Kaya Bork / Rüdiger Horstkorte / Faramarz Dehghani / Christian Scheller

International Journal of Molecular Sciences, Vol 15, Iss 10, Pp 18453-

2014 Volume 18465

Abstract: 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 ... ...

Abstract	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.
Keywords	nimodipine ; neuroprotection ; Neuro2a ; stress ; surgery ; Chemistry ; QD1-999 ; Science ; Q
Subject code	610
Language	English
Publishing date	2014-10-01T00:00:00Z
Publisher	Multidisciplinary Digital Publishing Institute
Document type	Article ; Online
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