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Introduction
Sina C. Rosenkranz currently works as a RG leader at the Institute of Neuroimmunology and Multiple Sclerosis (INIMS). Her work focuses on the molecular basis of neuroprotective behavioral interventions, such as exercise and hypoxia.
Additional affiliations
March 2019 - June 2019
January 2012 - present
July 2007 - December 2011
Education
October 2004 - November 2011
Publications
Publications (54)
Background
Despite the evidence of beneficial effects of physical activity (PA), people with multiple sclerosis (pwMS) are less physically active than the general population. To increase PA in pwMS, we developed a structured individually tailored PA promotion program which is conducted within clinical practice in a university-based outpatient clini...
Aim: This article is based on our previous research, which was presented as a poster at the ECTRIMS Congress 2018 and published as a conference abstract (https://www.professionalabstracts.com/ectrims2018/iplanner/#/presentation/1698). Cognitive-motor interference (CMI) has been observed in both healthy controls (HC) and persons with multiple sclero...
Background
As exercise exerts neurobiological and immunomodulatory effects, it might also act as a disease-modifying intervention in MS. However, a clear mechanistic link between exercise and disease-modifying effects in MS has yet to be established.
Objective
Establish recommendations for future mechanistic exercise studies in MS.
Methods
In reg...
Background
Neurodegeneration in multiple sclerosis (MS) affects the visual system but dynamics and pathomechanisms over several years especially in primary progressive MS (PPMS) are not fully understood.
Methods
We assessed longitudinal changes in visual function, retinal neurodegeneration using optical coherence tomography, MRI and serum NfL (sNf...
Background
Neurodegeneration leads to continuous accumulation of disability in progressive Multiple Sclerosis (MS). Exercise is considered to counteract disease progression, but little is known on the interaction between fitness, brain networks and disability in MS.
Objective
The aim of this study to explore functional and structural brain connect...
Sarcoidosis is the most frequent immunologically related granulomatous disease and can serve as a model for understanding diseases within this category. The evidence on the diagnostics and treatment is so far limited. It is therefore all the more important that two new and significant guidelines on diagnosis and treatment of sarcoidosis were publis...
Die Sarkoidose ist die häufigste immunologisch bedingte Granulomatose und kann beispielhaft für das Verständnis von Erkrankungen aus diesem Formenkreis herangezogen werden. Die Evidenz zur Diagnostik und Therapie ist bisher limitiert. Umso bedeutender ist es, dass in den letzten 2 Jahren gleich 2 neue Leitlinien zur Diagnose und Therapie veröffentl...
Adenine nucleotides, such as adenosine triphosphate (ATP), adenosine diphosphate (ADP), as well as the nucleoside adenosine are important modulators of neuronal function by engaging P1 and P2 purinergic receptors. In mitral cells, signaling of the G protein-coupled P1 receptor adenosine 1 receptor (A1R) affects the olfactory sensory pathway by regu...
Although most of the progressive multifocal leukoencephalopathy (PML) cases in sarcoidosis patients are explained by the treatment with immunosuppressive drugs, PML is also reported in treatment-naive sarcoidosis patients, which implies a general predisposition of sarcoidosis patients for PML. Indeed, it was shown that active sarcoidosis patients h...
Background
The human cytokine erythropoietin conveys neuroprotection in animal models but has shown ambiguous results in phase 2 clinical trials in patients with optic neuritis. We assessed the safety and efficacy of erythropoietin in patients with optic neuritis as a clinically isolated syndrome in a multicentre, prospective, randomised clinical t...
Background: Walking disability is one of the most frequent and burdening symptoms of progressive multiple sclerosis (MS). Most of the exercise intervention studies that showed an improvement in mobility performance were conducted in low to moderately disabled relapsing–remitting MS patients with interventions using the legs. However, MS patients wi...
Background
Impairment of visual function is one of the major symptoms of people with multiple sclerosis (pwMS). A multitude of disease effects including inflammation and neurodegeneration lead to structural impairment in the visual system. However, the gold standard of disability quantification, the expanded disability status scale (EDSS), relies o...
While transcripts of neuronal mitochondrial genes are strongly suppressed in central nervous system inflammation, it is unknown whether this results in mitochondrial dysfunction and whether an increase of mitochondrial function can rescue neurodegeneration. Here we show that predominantly genes of the electron transport chain are suppressed in infl...
Background: Progressive multifocal leukoencephalopathy (PML) caused by JCV is a rare but frequently fatal disease of the central nervous system, usually affecting immunocompromised individuals. Our study aims to expand the data on patient characteristics, diagnosis, clinical course, possible PML-directed treatment, and outcome of patients with PML...
Background:
Instrumented assessment of motor symptoms has emerged as a promising extension to the clinical assessment of several movement disorders. The use of mobile and inexpensive technologies such as some markerless motion capture technologies is especially promising for large-scale application but has not transitioned into clinical routine to...
BACKGROUND
Instrumented assessment of motor symptoms has emerged as a promising extension to the clinical assessment of several movement disorders. The use of mobile and inexpensive technologies such as some markerless motion capture technologies is especially promising for large-scale application but has not transitioned into clinical routine to d...
Background: Physical activity (PA) has beneficial effects on many disease related symptoms in people with multiple sclerosis (pwMS). Physical parameters - such as muscle strength, endurance, and balance - as well as fatigue, depression and neurocognitive functioning, can be positively influenced by regular PA. Nevertheless, pwMS are less physically...
Blood-brain barrier (BBB) dysfunction is critically involved in determining the extent of several central nervous systems (CNS) pathologies and here in particular neuroinflammatory conditions. Inhibiting BBB breakdown could reduce the level of vasogenic edema and the number of immune cells invading the CNS, thereby counteracting neuronal injury. Tr...
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that evokes calcium release from intracellular organelles by the engagement of calcium release channels, including members of the Transient Receptor Potential (TRP) family, such as TRPML1, the (structurally) related Two Pore Channel type 1 (TPC1) and TPC2 channels as well a...
Central nervous system (CNS) inflammation in multiple sclerosis (MS) drives neuro-axonal loss resulting in irreversible disability. While transcripts of mitochondrial genes are strongly suppressed in neurons during CNS inflammation, it is unknown whether this results in mitochondrial dysfunction and whether interventions that increase mitochondrial...
Exercise as a subset of physical activity is a cornerstone in the management of multiple sclerosis (MS) based on its pleotropic effects. There is an exponential increase in the quantity of research on exercise in MS, yet a number of barriers associated with study content and quality hamper rapid progress in the field. To address these barriers and...
Identifying T cell clones associated with human autoimmunity has remained challenging. Intriguingly, many autoimmune diseases, including multiple sclerosis (MS), show strongly diminished activity during pregnancy, providing a unique research paradigm to explore dynamics of immune repertoire changes during active and inactive disease. Here, we chara...
Multiple sclerosis (MS) is characterized by inflammatory insults that drive neuroaxonal injury. However, knowledge about neuron-intrinsic responses to inflammation is limited. By leveraging neuron-specific messenger RNA profiling, we found that neuroinflammation leads to induction and toxic accumulation of the synaptic protein bassoon (Bsn) in the...
Background
Only few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in multiple sclerosis.
Objective and Methods
This randomized controlled trial with 34 patients in the intervention group (IG) (mean: 38.2 years (±9.6)) and 34 patients in the control group (CG) (mean: 39.6 years (±9.7)) aimed t...
Background: Only few aerobic exercise intervention trials specifically targeting cognitive functioning have been performed in MS.
Objective and methods: This randomized controlled trial aimed to determine the effects of aerobic exercise on cognition in relapsing-remitting MS. The primary outcome was verbal memory (Verbal learning and memory test, V...
Primary progressive multiple sclerosis (PPMS) shows a highly variable disease progression with poor prognosis and a characteristic accumulation of disabilities in patients. These hallmarks of PPMS make it difficult to diagnose and currently impossible to efficiently treat. This study aimed to identify plasma metabolite profiles that allow diagnosis...
Workflow and summary of metabolomic profiling. (A) General workflow in data analysis. (B) Pie chart illustrating the percentage of putatively identified metabolites from each metabolite class, classified according to KEGG, Lipidmaps and HMDB. In total 534 metabolites were analysed. (C) PLS-DA scores plot of all 534 metabolites in HC cohort A (n = 1...
Linear model fit of PPMS marker levels and age of all analyzed individuals in PPMS cohorts A and B. Utilized linear model to fit correlation between PPMS marker levels and ageing. Black: Linear model for all data points, light red: linear model for HC cohort A, green: linear model for HC cohort B, blue: linear model for PPMS cohort A, purple: linea...
Inter-cohort dependencies determined by chi-square test for gender and one-way ANOVA for age, EDSS and disease duration (DD). Comparisons with significant p-values (p-value < 0.05) are highlighted in bold red.
PPMS marker levels and sex dependency in all individuals analyzed. Utilized one way ANOVA with Tukey’s post hoc test to compute differences between PPMS marker levels and sex in all groups. ∗Metabolites with significantly different levels between males and females (p-value < 0.05), ∗∗Metabolites with significantly different levels between males and...
Linear model fit of PPMS marker levels and age of all analyzed individuals in the RRMS cohort. Utilized linear model to fit correlation between PPMS marker levels and ageing. Black: Linear model for all data points, green: linear model for HC, orange: linear model for RRMS. Grey areas around the lines indicate the 0.95 confidence interval. Metaboli...
Cohorts. Patient information from investigated RRMS, PPMS, PD cohorts including age and gender. A disease duration of 0 corresponds to less than 1 year (∗.xlsx file).
Plasma metabolites identified in PPMS cohorts A and B (∗.xlsx file).
Model parameters for the tested models and their corresponding p-values after sample-label permutation test.
Metabolites with significant changes between HC and PPMS patients (A and B cohorts) their corresponding AUC values and VIP score ranks for component 1 and 2. Univariate AUCs and 95% CI (500 bootstrapping) calculated using MetaboAnalyst.
PPMS marker measured in RRMS, intensity levels in the RRMS cohort. P-values determined by Welch’s t-test, p-value adjustment for multiple comparison using Benjamini and Hochberg (FDR) adjustment (∗.xlsx file).
Extracted ion chromatograms of metabolites contributing to the specific PPMS signature.
Linear model fit of PPMS marker levels and age of all individuals analyzed in the PD cohort. Utilized linear model to fit correlation between PPMS marker levels and ageing. Black: Linear model for all data points, green: linear model for HC, purple: linear model for PD. Grey areas around the lines indicate the 0.95 confidence interval. Metabolites...
PPMS marker in PPMS patients compared to RRMS and PD patients. First p-value is determined by one-way ANOVA with Tukey’s post hoc with correction for multiple testing per metabolite. Metabolites with p-values < 0.05 are highlighted in bold green. Second p-value has been corrected (FDR) for all comparison including all metabolites.
Pathway analysis of identified changes in PPMS patients compared to healthy controls (HC). Pathway information retrieved from KEGG. Significantly altered metabolites are highlighted in dark red rectangles including the corresponding KEGG ID. Grey font indicates involved enzymes, dashed grey line indicates additional reactions which are not displaye...
MS/MS fragments used for PPMS marker identification. Identities confirmed by available authentic standards (validation level 1). MS/MS spectra were matched against online databases such as Metlin and MassBank (validation level 2) or against in silico fragmentation spectra (validation level 3) retrieved from Metfrag, CFM-ID and/or CSI:FingerID with...
PPMS marker measured in PD, intensity levels in the PD cohort. P-values determined by Welch’s t-test, p-value adjustment for multiple comparison using Benjamini and Hochberg (FDR) adjustment (∗.xlsx file).
Metabolite levels with significant changes between HC and PPMS patients measured in the longitudinal PPMS cohort (∗.xlsx file).
Background:
Fingolimod can lead to increased risk of cardiac events such as bradycardia or atrioventricular (AV) block.
Objective:
Evaluate acute and long-term effects of fingolimod on heart rhythm (HR), heart rate variability (HRV) and development of AV-blocks.
Methods:
In 64 patients with relapsing-remitting multiple sclerosis Holter ECG mon...
Background:
New diagnostic criteria of Multiple Sclerosis (MS) increase the number of patients being diagnosed with MS while a substantial part might not convert to clinically definite MS (CDMS).
Objective:
Diagnostic accuracy of the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an unselected cohort of patients in whom...
Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune demyelinating disease of the CNS that predominantly affects the optic nerves and the spinal cord.¹ Because of the severity and poor recovery of attacks, aggressive immunosuppressive agents are used early in the clinical course to reduce relapse frequency. Apart from class...
Background:
Clinical studies have suggested beneficial effects of exercise on cognitive function in ageing adults and neurodegenerative diseases such as dementia. Recent work indicates the same for progressive multiple sclerosis (MS), an inflammatory and degenerative disease of the central nervous system (CNS). The biological pathways associated w...
Die Inzidenz von Antikörper-assoziierten Enzephalitiden hat in den letzten Jahren stetig zugenommen. Dabei ist es wichtig, zwischen Antikörpern, die gegen intrazelluläre Proteine gerichtet sind und Antikörpern gegen neuronale Oberflächenproteine zu differenzieren, da sich die damit assoziierten Enzephalitiden sowohl in der Pathogenese als auch der...
Alzheimer's disease (AD) is the most common form of dementia in the elderly with progressive cognitive decline and memory loss. According to the amyloid-hypothesis, AD is caused by generation and subsequent cerebral deposition of β-amyloid (Aβ). Aβ is generated through sequential cleavage of the transmembrane Amyloid-Precursor-Protein (APP) by two...