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MIF protects from postoperative complications after cardiac surgery

Complex heart surgery may lead to organ dysfunction such as acute kidney injury (AKI) or ischemic stroke. A researcher team led by Aachen University and the Bernhagen lab found that patients with high blood levels of the cytokine MIF had a reduced risk of developing AKI. MIF was protective in experimental AKI by reducing oxidative stress and necroptosis. The study is published in this week’s issue of Sci Transl Med…. [mehr...]

HTRA1 loss-of-function in CADASIL

Isolation of CADASIL patient brain vessels in combination with proteome analysis identified loss of HTRA1 proteolytic function as a critical step in the development of disease pathology providing novel insights into the molecular mechanisms of cerebral small vessel diseases... [mehr...]

A novel link between the chemokine MIF and B lymphocytes in atherosclerosis

The Bernhagen lab at ISD together with collaborating labs uncovered a previously unrecognized connection between the atherogenic chemokine-like cytokine MIF and B cell function in atherosclerosis. The study appeared in last week’s volume of The FASEB ... [mehr...]

Stroke exacerbates atherosclerosis.

The Liesz lab discovered that an experimental stroke leads to progression and increased vulnerability of atherosclerotic plaques and identified the underlying immunological mechanism. This study which might explain the increased risk of recurrent stroke events is published in this week’s issue of Science Translational Medicine... [mehr...]

22 novel risk loci for stroke identified.

Studying more than 520.000 individuals from around the world an international GWAS effort lead by ISD investigators identified 22 novel risk loci for stroke. The results provide novel targets for mechanistic studies and perspectives for drug development... [mehr...]

Increased free water in small vessel disease brains

Diffusion changes are a major hallmark of cerebral small vessel disease. A recent study from ISD investigators shows that these changes are determined by an increase of free water in the tissue... [mehr...]

Protective hub connectivity in Alzheimer's disease

Some patients with Alzheimer's disease show a remarkable resilience against the impact of brain pathology. A new ISD study revealed a hub region in the brain that plays a key role in delaying dementia symptoms even in genetically caused AD... [mehr...]

The choroid plexus is a key cerebral invasion route for T cells after stroke.

ISD researchers have identified the choroid plexus as a previously unrecognized key structure for cerebral T cell invasion into the brain after stroke. These findings are of high relevance for clinical trials targeting immune cell infiltration in stroke patients... [mehr...]

Novel Risk Loci for Alzheimer's Disease

A multinational consortium including ISD researchers identified rare coding variants associated with Alzheimer's disease (AD). The variants are situated in genes that are highly expressed in microglia and highlight a role of microglia-mediated innate immune responses in AD... [mehr...]

miRNA set as a novel biomarker for ischemic stroke

Using RNA sequencing and qRT-PCR in three independent samples of acute ischemic stroke patients ISD researchers established a set of 3 circulating microRNAs (miR-125a-5p, miR-125b-5p and miR-143-3p) as a promising blood-based diagnostic marker for the early phase of ischemic stroke [mehr...]

Atheroprotective function for COP9 signalosome

Applying preclinical models of atherosclerosis and myeloid-specific gene knockout, an international team led by ISD researchers found that the deNEDDylase CSN5, a subunit of the COP9 signalosome that controls cellular protein degradation processes, has protective functions in the pathogenesis of atherosclerosis... [mehr...]

Role of α-1-antitrypsin in large artery stroke

An exome-wide association study led by ISD investigators found M1(A213V) in SERPINA1 to be associated with stroke, with the variant changing its functional dynamics towards neutrophil elastase in the presence of lipid-containing plasma [mehr...]

Neural substrate of cognitive reserve in Alzheimer’s

More years of education is associated with reduced risk of Alzheimer’s dementia. ISD researchers found that higher connectivity of a hub region in the frontal cortex may subserve protective effects of education... [mehr...]

Homoarginine Improves Function in Heart Failure

Low homoarginine (HA) is an emerging biomarker for cardiovascular diseases. In collaboration, Dorothee Atzler from the Vascular Biology team at the ISD showed that HA is more than a bystander biomarker, since HA-supplementation helps to support cardiac function in chronic heart failure in mice [mehr...]

Tracing the neuroimmune response in AD

The emergence of neuroinflammation in the pathological cascade of Alzheimer’s disease is still unknown. The teams of C. Haass (DZNE) and M. Ewers (ISD) demonstrated dynamic changes in the novel biomarker of microglia activity, called TREM2, to be closely coupled to neurodegeneration occurring several years before symptom onset [mehr...]

Interfering with the Chronic Immune Response

Traumatic brain injury (TBI) frequently causes chronic complications including epilepsy and dementia. A new study by Ali Ertürk and colleagues shows that TBI causes a long-lasting brain immune response that parallels neurodeneration. Limiting the invasion of immune cells prevents neurodegeneration and improves motor function. [mehr...]

New biomarker for small vessel disease

In a large, collaborative study, ISD researchers established and validated a novel imaging biomarker for cerebral small vessel disease. The marker is based on skeletonization of white matter tracts and diffusion histograms. [mehr...]

Seeing through entire organisms

Ali Ertürk and his team developed novel technology that allows making entire organs and organisms transparent. The new method provides the basis to map neuronal, glial, and vascular connections in the entire lab animals and in human brains. The work was published in Nature Methods and highlighted by Nature Press. [mehr...]

Role of the gut microbiome in stroke

A recent study by ISD researchers reveals a bidirectional interaction between the brain and the gut microbiome after experimental stroke. Post-stroke dysbiosis induces a neurotoxic immune response. The study was published in the Journal of Neuroscience and was featured by various media reports [mehr...]

Tract-specific WMH and network function in AD

A study by Michael Ewers and team published in Alzheimer's and Dementia shows that age-related white matter hyperintensities (WMH) in specific vulnerable WM tracts are associated with impaired network function in patients with Alzheimer's disease (AD). [mehr...]

Cell diversity revealed by single cell RNAseq

In an article published in Cell Reports Ozgun Gokce and colleagues reveal unexpected diversity of striatal cells using scRNAseq. They also describe continuous expression gradients within individual cell types. [mehr...]

Role of Vascular Factors in Migraine

A Genome-wide association study with involvement of ISD investigators has identified 38 susceptibility loci for migraine including 28 novel loci. The results lend further weight to a vascular etiology of migraine and emphasize genetic overlap with stroke [mehr...]

Novel risk loci for large and small vessel stroke

In a series of genome-wide association studies (GWAS) ISD investigators in collaboration with other scientists from the international stroke genetics consortium (ISGC) recently identified several risk loci for ischemic stroke. The work is published in three papers in Lancet Neurology and Neurology [mehr...]

TREM2 in prodromal AD

Mutations in the TREM2 gene are associated with a threefold risk of AD dementia. A multicenter study led by M. Ewers (ISD) & C. Haass (DZNE) suggests that soluble TREM2 in cerebrospinal fluid is a novel biomarker of neurofinflammation, altered early in sporadic AD. [mehr...]

Role of pericytes in CADASIL

A study by Ghosh and colleagues (Plesnila lab) published in the Annals of Neurology demonstrates that pericytes are critically involved in the initiation of CADASIL, an inherited small vessel disease. Hence, protecting pericytes may represent a novel therapeutic strategy for this disorder [mehr...]

E-book on inflammatory mechanisms in stroke

An E-book on inflammation in brain injury, edited by A. Liesz (ISD) and C. Kleinschnitz (Würzburg), has been published at Frontiers in Cellular Neuroscience. The E-book consists of 25 articles by >100 authors covering diverse aspects of post-stroke immunity. [mehr...]

The first preclinical RCT

An international team coordinated by Arthur Liesz (ISD) completed the first preclinical RCT as a response to the „replication crisis“ in translational research. The study validated the efficacy of the anti-CD49d antibody in brain ischemia. The results are published in this week’s issue of Science Translational Medicine [mehr...]

Shared genetic basis for migraine and stroke

By analyzing genome-wide data from stroke and migraine consortia ISD investigators showed that common variants at a substantial number of genetic loci influence risk of both ischemic stroke and migraine, with strongest overlap between migraine without aura and both large artery stroke and cardioembolic stroke. [mehr...]

Remote cortical effects after ischemic stroke

Remote effects of infarcts are considered determinants of stroke outcome. This study demonstrates loss of both white and grey matter in distant brain regions connected to infarcts, suggesting secondary neurodegeneration as a key mechanism underlying remote changes after stroke. [mehr...]

Cysteine-sparing NOTCH3 mutations

The role of cysteine-sparing NOTCH3 mutations in CADASIL has been debated for a long time. Using single-particle analysis ISD investigators now demonstrated enhanced aggregation behavior similar to typical cysteine mutations. Their work published in the STROKE journal has implications for diagnostic decision-making. [mehr...]

Alarmins in brain-immune communication

A new study by A. Liesz and colleagues identifies alarmins, in particular HMGB1, as key mediators of the complex peripheral immune alterations after stroke. Alarmins are released from necrotic brain tissue to the circulation and show profound effects both in mice and humans [mehr...]

Cerebral SVD and TGF-β signaling

A new study published in the PNAS journal links a reduction of TGF-β signaling to the hereditary small vessel disease CARASIL and provides a mechanism by which loss-of-function mutations in HTRA1 interfere with release of TGF-β from the extracellular matrix [mehr...]

HDAC9 and Atherosclerosis

A new study by ISD investigators published in the STROKE journal shows that HDAC9 represents the disease-relevant gene at the stroke risk locus on 7p21.1. Our findings offer novel mechanistic insights and have implications for the development of novel preventive strategies [mehr...]

A new twist in CADASIL pathogenesis

A study led by Christof Haffner (ISD) and published in Acta Neuropathologica Communications sheds light on the molecular mechanism underlying the inherited small vessel disease CADASIL [mehr...]

Strategic white matter tracts in vascular cognitive impairment

A study conducted by ISD investigators highlights the relevance of lesion location in vascular cognitive impairment (VCI). Voxel-based lesion-symptom mapping and Bayesian network analysis identified two major white matter [mehr...]

Stroke risk prediction through genetic risk functions

In two companion articles published this week in STROKE ISD investigators together with researchers from the CHARGE consortium show that multi-locus genetic risk scores based on common variants for vascular risk factors can discriminate stroke patients. [mehr...]

Detection of Preclinical Alzheimer’s Disease

Results of a study by Ewers & colleagues suggest that reduced FDG-PET and subtle changes in the mental ability of cognitively normal elderlies predict the future development of dementia symptoms. These tests may be sensitive to the asymptomatic preclinical stage of Alzheimer’s disease [mehr...]

Shared genetic susceptibility to stroke and CAD

By analyzing genome-wide data from the METASTROKE and CARDIoGRAM consortia ISD investigators showed that common variants at a substantial number of genetic loci influence risk of both ischemic stroke and coronary artery disease (CAD). This includes novel risk loci for ischemic and large artery stroke [mehr...]

New Publication in The Journal of Neuroscience

A study by Arthur Liesz and colleagues, published in the October issue of The Journal of Neuroscience, describes the use of histone deacetylase inhibitors (HDACi) to boost regulatory T cells (Treg), a specialised cell population orchestrating the immune reaction after ischemic brain injury [mehr...]

Incident lacunes and the WMH penumbra

A study by Marco Düring and colleagues, published in the BRAIN journal, identifies the edge of white matter hyperintensities (WMH) as a predilection site for lacunes. Their observations offer insights into the mechanisms underlying WMH and lacunes and refine the concept of the WMH penumbra [mehr...]

STandards for ReportIng Vascular Changes on NEuroimaging (STRIVE)

In a united approach specialists in vascular imaging established neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. The results are published in the August issue of Lancet Neurology. (Funding: ... [mehr...]

New findings on protective effects in Alzheimer's Disease

A study by Michael Ewers & colleagues, published this week in NEUROLOGY, suggests that higher levels of education have protective effects (cognitive reserve) in AD. The authors found that in the early stage of AD, elderly subjects with more years of education remained cognitively normal despite more severe brain ... [mehr...]


Institut für Schlaganfall-
und Demenzforschung (ISD)

Klinikum der Universität München

Prof. Dr. med.
Martin Dichgans

Feodor-Lynen-Straße 17
D-81377 München

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