Ausgewählte Publikationen

Single-cell profiling identifies myeloid cell subsets with distinct fates during neuroinflammation

Science 363: pii.eaat7554 (2019)

In collaboration with the group of Marco Prinz we use a single cell RNAseq approach to reveal the evolution of myeloid cell diversity during different stages of neuroinflammation. Furthermore we use in vivo imaging to record the contact patterns of distinct myeloid cell subsets with T cells in neuroinflammatory lesions. [mehr...]
 

Calcium influx through plasma-membrane nanoruptures drives axon degeneration in a model of multiple sclerosis.

Neuron doi: 10.1016/j.neuron.2018.12.023

Here we use in vivo calcium imaging in a multiple sclerosis model to show that cytoplasmic calcium levels determine the choice between axon loss and survival. Calcium can enter the axon through nanoscale ruptures of the axonal plasma membrane that are induced in inflammatory lesions. [mehr...]
 

Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model.

Nature Neuroscience 21:1196-1208 (2018)

Here we use an in vivo imaging approach to follow the evolution of phagocyte phenotypes in neuroinflammatory lesions. By tracking phagocytes over time we can show that individual phagocytes switch their phenotype as lesions move from expansion to resolution. [mehr...]
 

Myelinosome formation represents an early stage of oligodendrocyte damage in multiple sclerosis and its animal model.

Nat Commun. 2016 Nov 16;7:13275. doi: 10.1038/ncomms13275.

Here we investigate how oligodendrocyte damage is initiated in multiple sclerosis (MS) and EAE. We can show that oligodendrocyte damage spreads centripetally and that the formation of focal myelin outfoldings that we call “myelinosomes” is an early sign of oligodendrocyte damage both in MS and EAE. [mehr...]
 

Loss of Myelin Basic Protein Function Triggers Myelin Breakdown in Models of Demyelinating Diseases.

Cell Rep. 2016 Jul 12;16(2):314-22.

In collaboration with the group of Mikael Simons we show that the aberrant transition of MBP molecules from their cohesive state to their non-adhesive state underlies the vesicular disruption of the myelin sheath in models of demyelinating disease. [mehr...]
 

Origin, fate and dynamics of macrophages at central nervous system interfaces.

Nat Immunol. 2016 May 2. doi: 10.1038/ni.3423

Here we contribute to the characterization of perivascular, subdural and choroid plexus macrophages and reveal their dynamic behaviour in the intact central nervous system. [mehr...]
 

Reconstruction of single cortical projection neurons reveals primary spine loss in multiple sclerosis

Brain. 2016 Jan;139(Pt 1):39-46. doi: 10.1093/brain/awv353. Epub 2015 Dec 14.

Here we we use confocal microscopy of Golgi-Cox impregnated tissue sections to reconstruct single cortical projection neurons in brain sections from multiple sclerosis and control patients. Our study reveals a widespread loss and pronounced loss of dendritic spines that occurs independently of cortical demyelination and axon loss and indicates the presence of a primary synaptic pathology in multiple sclerosis. [mehr...]
 

Astrocyte Depletion Impairs Redox Homeostasis and Triggers Neuronal Loss in the Adult CNS

Cell Rep. 2015 Sep 1;12(9):1377-84. doi: 10.1016/j.celrep.2015.07.051.

Although the importance of reactive astrocytes during CNS pathology is well established, the function of astroglia in adult CNS homeostasis is less well understood. With the use of conditional, astrocyte-restricted protein synthesis termination, we found that selective paralysis of GFAP(+) astrocytes in vivo led to rapid neuronal cell loss and severe motor deficits. [mehr...]
 

Role of the innate and adaptive immune responses in the course of multiple sclerosis

Lancet Neurology 14: 406-419 (2015)

In this review the role of the innate and adaptive immune responses in the course of multiple sclerosis is discussed. [mehr...]
 

Pervasive axonal transport deficits in multiple sclerosis models

Neuron 84: 1183-1190 (2014)

Here we visualize the dynamics of organelles in individual spinal axons and reveal widespread impairment of organelle transport in MS models. Transport deficits precede structural alterations of axons, myelin or microtubules. They persist in chronic MS models and lead to a reduced distal organelle density. [mehr...]
 

An assay to image neuronal microtubule dynamics in mice

Nature Communications 5:4827 doi:10.1038/ncomms5827 (2014)

Here we contribute to the development of a novel in vivo assay that allows visualizing neuronal microtubule dynamics in the peripheral and central nervous system. [mehr...]
 

A recoverable state of axon injury persists for hours after spinal contusion in vivo

Nature Communications 5:5683 doi:10.1038/ncomms6683 (2014)

Here we use spinal in vivo imaging to show that axons persist in a metastable state for hours after spinal contusion injury. During this time the intra-axonal calcium dynamics determine the axonal fate. Those axons that manage to re-establish calcium homoestasis will survive longterm while those that fail to do so will degenerate. This study identifies an inherent self-preseravtion process in contused axons and a window of opportunity for rescuing axonal connectivity after contusion injury. [mehr...]
 

A unified cell biological perspective on axon-myelin injury

Journal of Cell Biology 206, 335-345 (2014)

Here we review recent advances in our understanding of the mechanisms that mediate axon and myelin injury in neuroinflammatory conditions and propose that the close cell biological interconnection of the axon-myelin unit could help explain the spread of pathology in advanced stages of MS. [mehr...]
 

Multparametric optical analysis of mitochondrial redox signals during neuronal physiology and pathology in vivo

Nature Medicine 20, 555-560 (2014)

Here we establish a novel multiparametric imaging approach that allows us to visualize and mechanistically dissect mitochondrial redox signals with high temporal and spatial resolution in the living nervous system. [mehr...]
 

STAT3 promotes corticospinal remodelling and functional recovery after spinal cord injury

EMBO Rep. 2013 Sep 30;14(10):931-7. doi: 10.1038/embor.2013.117

Here we show that viral gene transfer of the transcription factor STAT3 can induce remodeling if unlesioned fibers and thereby improve functional recovery after spinal cord injury. [mehr...]
 

Neuroprotective intervention by interferon-γ blockade prevents CD8+ T cell-mediated dendrite and synapse loss

J Exp Med. 2013 Sep 23;210(10):2087-103. doi: 10.1084/jem.20122143

Here we show that CD8+ T cells induce neuronal deafferentiation in a viral encephalitis model via the secretion of interferon gamma. [mehr...]
 

Cellular, subcellular and functional in vivo labeling of the spinal cord using vital dyes

Nature Protocols 8, 481–490 (2013) doi:10.1038/nprot.2013.022

Here we show how vital dyes can be used to label and image cells, subcellular organelles and effector molecules in the spinal cord of living mice. [mehr...]
 

Axonal transport deficits and degeneration can evolve independently in mouse models of amyotrophic lateral sclerosis

Proc Natl Acad Sci U S A. 2012 Mar 13;109(11):4296-301. Epub 2012 Feb 27

Here, we investigate the relation between axonal transport and degeneration in an animal model of ALS. [mehr...]
 

Near-infrared branding efficiently correlates light and electron microscopy

Nat Methods. 2011 Jun 5;8(7):568-70

Here, we describe a new technique that uses fiduciary marks set by a 2-photon laser to correlate light and electron microscopic images. [mehr...]
 

In vivo imaging reveals a phase-specific role of STAT3 during central and peripheral nervous system axon regeneration

Proc Natl Acad Sci U S A. 2011 Apr 12;108(15):6282-7

Here, we show that the transcription factor STAT3 regulates the initiation but not the elongation phase of axonal regeneration in the PNS and CNS. [mehr...]
 

A reversible form of axon damage in experimental autoimmune encephalomyelitis and multiple sclerosis

Nature Medicine 2011 Vol. 17 No. 4

Here, we use in vivo multiphoton imaging to identify a novel form of axonal degeneration that contributes to axon loss in multiple sclerosis and its animal model. [mehr...]
 

Ex vivo imaging of motor axon dynamics in murine triangularis sterni explants

Nat Protoc. 2008;3(10):1645-53

Here, we describe a neuromuscular explant system that is particularly suited for ex vivo imaging. [mehr...]
 

Imaging axonal transport of mitochondria in vivo

Nat Methods. 2007 Jul;4(7):559-61. Epub 2007 Jun 10

Here, we establish a novel approach that allows to image the transport of fluorescently labelled mitochondria in the intact nervous system. [mehr...]
 

In vivo imaging of single axons in the mouse spinal cord

Nat Protoc. 2007;2(2):263-8

Here, we describe how to image fluorescently labelled axons in the spinal cord of living mice. [mehr...]
 

In vivo imaging of the diseased nervous system

Nat Rev Neurosci. 2006 Jun;7(6):449-63

Here, we discuss how in vivo imaging techniques can help us to better understand neurological conditions. [mehr...]
 

Transgenic labeling of the corticospinal tract for monitoring axonal responses to spinal cord injury

Nat Med. 2005 Dec;11(12):1355-60. Epub 2005 Nov 13

Here, we describe how mice with a fluorescently labelled corticospinal tract can improve the analysis of axonal plasticity after spinal cord injury. [mehr...]
 

In vivo imaging of axonal degeneration and regeneration in the injured spinal cord

Nat Med. 2005 May;11(5):572-7. Epub 2005 Apr 10

Here, we visualize for the first time fluorescently labelled axons and their response to transection in the spinal cord of living mice. [mehr...]
 
 
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Prof. Dr.

Reinhard Hohlfeld

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Prof. Dr.

Martin Kerschensteiner

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