A5004536641- Neuroinflammation and Neurodegeneration Mechanisms
- Alzheimer's disease research and treatments
- Neurogenesis and neuroplasticity mechanisms
- Cerebrospinal fluid and hydrocephalus
- Neuroscience and Neural Engineering
- Transcranial Magnetic Stimulation Studies
- Tryptophan and brain disorders
- Nerve injury and regeneration
- Peroxisome Proliferator-Activated Receptors
- Acute Ischemic Stroke Management
- Immune cells in cancer
- Intracerebral and Subarachnoid Hemorrhage Research
- Neonatal and fetal brain pathology
- Dementia and Cognitive Impairment Research
- Adipose Tissue and Metabolism
- Ferroptosis and cancer prognosis
- Immune Response and Inflammation
- Neuroscience and Neuropharmacology Research
- Vestibular and auditory disorders
- Receptor Mechanisms and Signaling
- Endoplasmic Reticulum Stress and Disease
- Diet and metabolism studies
- Single-cell and spatial transcriptomics
- Cholesterol and Lipid Metabolism
- Muscle activation and electromyography studies
University of Helsinki
2019-2024
University of Eastern Finland
2018-2024
University Hospital Cologne
2012-2019
Max Planck Institute for Metabolism Research
2012-2019
Transcranial direct current stimulation (tDCS) is increasingly being used in human studies as an adjuvant tool to promote recovery of function after stroke. However, its neurobiological effects are still largely unknown. Electric fields known influence the migration various cell types vitro, but vivo remain be shown. Hypothesizing that tDCS might elicit recruitment cells cortex, we here studied rat brain vivo. Adult Wistar rats (n = 16) were randomized either anodal or cathodal for 5 10...
Neuroinflammation is strongly induced by cerebral ischemia. The early phase after the onset of ischemic stroke characterized acute neuronal injury, microglial activation, and subsequent infiltration blood-derived inflammatory cells, including macrophages. Therefore, modulation microglial/macrophage responses has increasingly gained interest as a potential therapeutic approach for stroke. In our study, we investigated effects peripherally administered interleukin 13 (IL-13) in mouse model...
Abstract Discovery of meningeal lymphatic vessels (LVs) in the dura mater, also known as dural LVs (dLVs) that depend on vascular endothelial growth factor C expression, has raised interest their possible involvement Alzheimer’s disease (AD). Here we find APdE9 and 5xFAD mouse models AD, amyloid-β (Aβ) is confined to blood dLV morphology or function not altered. The induction sustained atrophy hyperplasia AD mice by blocking overexpressing C, impaired improved, respectively, macromolecular...
Astrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source energy. Defective mitochondrial dysfunctions correlate with hippocampal neurodegeneration memory deficits in Alzheimer's disease (AD), but it is unclear whether metabolism can be targeted to prevent or treat disease. Here we show for first time an impairment human astrocytes derived from induced pluripotent stem...
Lipid peroxidation-initiated ferroptosis is an iron-dependent mechanism of programmed cell death taking place in neurological diseases. Here we show that a condensed benzo[b]thiazine derivative small molecule with arylthiazine backbone (ADA-409-052) inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic triggered by glutathione (GSH) depletion or peroxidase 4 (GPx4) inhibition neuronal lines. In addition, ADA-409-052 suppresses...
Timely relief of edema and clearance waste products, as well promotion anti-inflammatory immune responses, reduce ischemic stroke pathology, attenuate harmful long-term effects post-stroke. The discovery an extensive functional lymphatic vessel system in the outermost meningeal layer, dura mater, has opened up new possibilities to facilitate post-stroke recovery by inducing dural (dLV) growth via a single injection vector encoding vascular endothelial factor C (VEGF-C). In present study, we...
Transcranial direct current stimulation (tDCS) is used in numerous clinical studies and considered an effective versatile add‐on therapy neurorehabilitation. To date, however, the underlying neurobiological mechanisms remain elusive. In a rat model of tDCS, we recently observed polarity‐dependent accumulation endogenous neural stem cells (NSCs) stimulated cortex. Based upon these findings, hypothesized that tDCS may exert migratory effect on NSCs towards Using noninvasive imaging, here...
Abstract Previous studies have implicated several brain cell types in schizophrenia (SCZ), but the genetic impact of astrocytes is unknown. Considering their high complexity humans, are likely key determinants neurodevelopmental diseases, such as SCZ. Human induced pluripotent stem (hiPSC)‐derived differentiated from five monozygotic twin pairs discordant for SCZ and healthy subjects were studied alterations related to risk clinical manifestation astrocyte transcriptomics, neuron‐astrocyte...
Stroke is a leading cause of permanent disability worldwide. Despite intensive research over the last decades, key anti-inflammatory strategies that have proven beneficial in pre-clinical animal models often failed translation. The importance neutrophils as pro- and peripheral immune cells has been overlooked ischemic stroke. However, rapidly infiltrate into brain parenchyma after stroke secrete an array pro-inflammatory factors including reactive oxygen species, proteases, cytokines,...
Despite its extensive use in clinical studies, the molecular mechanisms underlying effects of transcranial direct current stimulation (tDCS) remain to be elucidated. We previously described subacute tDCS on immune- and stem cells rat brain. To investigate more immediate regulating those cellular responses, we treated rats with a single session either anodal or cathodal tDCS, analyzed gene expression by microarray; sham-stimulated served as control. Anodal increased several genes coding for...
The recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between immune and central nervous system. role of mLVs in modulating neuro-immune response following a traumatic brain injury (TBI), however, has not analyzed. Parenchymal T lymphocyte infiltration previously reported as part secondary events after TBI, suggestive an adaptive response. phenotype these cells remained mostly uncharacterized. In this study, we identified subpopulations...
Abstract Human astrocytes are multifunctional brain cells and may contribute to the pathophysiology of schizophrenia (SCZ). We differentiated from induced pluripotent stem monozygotic twins discordant for SCZ, found sex-specific gene expression signaling pathway alterations related particularly inflammation synaptic functions. While Ingenuity Pathway Analysis identified SCZ disease transmission changes in astrocytes, most consistent findings were collagen cell adhesion associated pathways....
Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) regulate the hypoxic induction of >300 genes required for survival and adaptation under oxygen deprivation. Inhibition HIF-P4H-2 has been shown to be protective in focal cerebral ischemia rodent models, while that HIF-P4H-1 no effects inactivation HIF-P4H-3 adverse effects. A transmembrane 4-hydroxylase (P4H-TM) is highly expressed brain contributes regulation HIF, but outcome its inhibition on stroke yet unknown. To study this, we...
The PSEN1 ΔE9 mutation causes a familial form of Alzheimer’s disease (AD) by shifting the processing amyloid precursor protein (APP) towards generation highly amyloidogenic Aβ42 peptide. We have previously shown that in human-induced pluripotent stem cell (iPSC)-derived astrocytes increases production and impairs cellular responses. Here, we injected mutant astrosphere-derived glial progenitors into newborn mice investigated mouse behavior at ages 8, 12, 16 months. While did not find...
Abstract Rationale The recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between immune and central nervous systems. role of mLVs in modulating neuro-immune response following a brain injury, however, has not analyzed. Parenchymal T lymphocyte infiltration previously reported as part secondary events after traumatic injury (TBI), suggestive an adaptive response. phenotype these cells remained mostly uncharacterized. In this study, we identified...
Species-specific differences in astrocytes and their Alzheimer disease-associated pathology may influence cellular responses to other insults. Herein, human glial chimeric mice were generated evaluate how disease predisposing genetic background contributes behavioral outcome brain after cortical photothrombotic ischemia.Neonatal (P0) immunodeficient of both sexes transplanted with induced pluripotent stem cell-derived astrocyte progenitors from patients carrying PSEN1 exon 9 deletion (PSEN1...
The central nervous system (CNS) has for long been considered to be devoid of proper lymphatic vascular system. However, recent studies suggest that meningeal vessels may take part into clearance waste products, macromolecules and immune cells systemic blood circulation. We set out investigate the contribution in drainage beta-amyloid (Aß) protein from brain hypothesized lack Alzheimer's disease (AD) transgenic mice would lead faster Aß accumulation. cross-bred amyloid plaque producing...