Refine
Has Fulltext
- yes (33)
Is part of the Bibliography
- yes (33)
Year of publication
Document Type
- Journal article (33)
Language
- English (33) (remove)
Keywords
- ischemic stroke (11)
- neuroinflammation (5)
- stroke (5)
- middle cerebral artery occlusion (4)
- deep brain stimulation (3)
- immunohistochemistry (3)
- inflammasome (3)
- mesencephalic locomotor region (3)
- neutrophils (3)
- photothrombotic stroke (3)
- platelets (3)
- thrombo-inflammation (3)
- GFAP (2)
- NLRP3 (2)
- acute ischemic stroke (2)
- blood brain barrier (2)
- blood–brain barrier (2)
- cognitive impairment (2)
- endoglin (2)
- glial fibrillary acidic protein (2)
- glycoprotein receptor Ib (2)
- hypoxia (2)
- ischemic penumbra (2)
- mechanical thrombectomy (2)
- neurofilament light chain (2)
- ASC (1)
- Alzheimer’s dementia (1)
- Biomarker (1)
- Brain atrophy (1)
- CD105 (1)
- CXCL4 (1)
- CXCL5 (1)
- CXCL7 (1)
- CXCL8 (1)
- CXCR2 (1)
- Cell Index (1)
- Chronic heart failure (1)
- Cognitive decline (1)
- FXIIa inhibitor rHA-Infestin (1)
- Gehirn (1)
- Glial fibrillary acidic protein (1)
- HBMEC (1)
- HMGB1 (1)
- IgG (1)
- MCC950 (1)
- MRI (1)
- Memory dysfunction (1)
- NAP-2 (1)
- NETs (1)
- NfL (1)
- Orai2 (1)
- PF4 (1)
- SB332235 (1)
- STEMI (1)
- Schlaganfall (1)
- T-cells (1)
- Thrombus (1)
- Vasodilatator-stimuliertes Phosphoprotein (1)
- Vasodilator-Stimulated Phosphoprotein (1)
- Western blot (1)
- age (1)
- albumin (1)
- alpha-7 nicotinic acetylcholine receptor (1)
- biomarker (1)
- biomarkers (1)
- blood (1)
- blood flow (1)
- blood-brain barrier (1)
- brain endothelium (1)
- cardiac magnetic resonance imaging (1)
- cerebral ischemia (1)
- cerebrovascular diseases (1)
- cerebrovascular disorders (1)
- chemokines (1)
- choline acetyltransferase (1)
- chronic heart failure (1)
- cluster analysis (1)
- coagulation factor XIIa (1)
- collagens (1)
- collateral circulation (1)
- contact activation system (1)
- contrast-enhanced MRI (1)
- demography (1)
- developmental signaling (1)
- emulsions (1)
- fluorine (1)
- gadofluorine (1)
- gadolinium-DTPA (1)
- glial damage (1)
- glycoprotein VI (1)
- glycoprotein receptor Ibα (1)
- heart failure (1)
- human brain endothelium (1)
- human cerebral endothelial cells (1)
- i.v. thrombolysis (1)
- in vivo imaging (1)
- infarction (1)
- infarction size (1)
- integrin α2 (1)
- integrins (1)
- intensity of attention (1)
- interleukin-8 (1)
- intracranial bleeding (1)
- iron oxide nanoparticles (1)
- ischemia/reperfusion injury (1)
- large vessel occlusion (1)
- leukocytes (1)
- macrophages (1)
- magnetic resonance imaging (1)
- multiple sclerosis (1)
- myocardial infarction (1)
- neurology (1)
- neuronal apoptosis (1)
- neuroprotection (1)
- occlusion (1)
- phosphorylated tau protein (1)
- platelet activation (1)
- platelet aggregation (1)
- preclinical research (1)
- prefrontal cortex (1)
- recombinant tissue-type plasminogen activator (1)
- renal function (1)
- reoxygenation (1)
- reperfusion injury (1)
- rt-PA (1)
- secondary infarct growth (1)
- serotonin (1)
- sex addiction (1)
- shedding (1)
- soluble endoglin (1)
- tMCAO (1)
- thrombemboli (1)
- thromboemboli (1)
- thrombosis (1)
- tight junctions (1)
- transient middle cerebral artery (1)
- transient middle cerebral artery occlusion (1)
- vascular homeostasis (1)
Institute
- Neurologische Klinik und Poliklinik (33)
- Institut für diagnostische und interventionelle Neuroradiologie (ehem. Abteilung für Neuroradiologie) (12)
- Rudolf-Virchow-Zentrum (8)
- Institut für Experimentelle Biomedizin (7)
- Medizinische Klinik und Poliklinik I (4)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (3)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (3)
- Institut für Klinische Epidemiologie und Biometrie (2)
- Kinderklinik und Poliklinik (2)
- Medizinische Klinik und Poliklinik II (2)
Sonstige beteiligte Institutionen
Background
Ischemic stroke immediately evokes a strong neuro-inflammatory response within the vascular compartment, which contributes to primary infarct development under vessel occlusion as well as further infarct growth despite recanalization, referred to as ischemia/reperfusion injury. Later, in the subacute phase of stroke (beyond day 1 after recanalization), further inflammatory processes within the brain parenchyma follow. Whether this second wave of parenchymal inflammation contributes to an additional/secondary increase in infarct volumes and bears the potential to be pharmacologically targeted remains elusive. We addressed the role of the NLR-family pyrin domain-containing protein 3 (NLRP3) inflammasome in the subacute phase of ischemic stroke.
Methods
Focal cerebral ischemia was induced in C57Bl/6 mice by a 30-min transient middle cerebral artery occlusion (tMCAO). Animals were treated with the NLRP3 inhibitor MCC950 therapeutically 24 h after or prophylactically before tMCAO. Stroke outcome, including infarct size and functional deficits as well as the local inflammatory response, was assessed on day 7 after tMCAO.
Results
Infarct sizes on day 7 after tMCAO decreased about 35% after delayed and about 60% after prophylactic NLRP3 inhibition compared to vehicle. Functionally, pharmacological inhibition of NLRP3 mitigated the local inflammatory response in the ischemic brain as indicated by reduction of infiltrating immune cells and reactive astrogliosis.
Conclusions
Our results demonstrate that the NLRP3 inflammasome continues to drive neuroinflammation within the subacute stroke phase. NLRP3 inflammasome inhibition leads to a better long-term outcome—even when administered with a delay of 1 day after stroke induction, indicating ongoing inflammation-driven infarct progression. These findings may pave the way for eagerly awaited delayed treatment options in ischemic stroke.