Refine
Has Fulltext
- yes (73)
Is part of the Bibliography
- yes (73)
Year of publication
Document Type
- Journal article (73) (remove)
Language
- English (73)
Keywords
- Neurobiologie (38)
- Medizin (8)
- active zone (4)
- Hypothalamus (3)
- Prostaglandine (3)
- TRH (3)
- blood pressure (3)
- Durchblutung (2)
- Gehirn (2)
- Mesenteric circulation (2)
- Neurophysiologie (2)
- cardiac output (2)
- closed head injury (2)
- contact-kinin system (2)
- heart rate (2)
- inflammation (2)
- rats (2)
- traumatic brain injury (2)
- 2-photon microscopy (1)
- Anaphylactic shock (1)
- Anaphylaxis (1)
- Autoradiography (1)
- Axonal degeneration (1)
- BN 52021 (1)
- Biowissenschaften (1)
- Blutdruck (1)
- Brain stem (1)
- Bruchpilot (1)
- C1-inhibitor (1)
- CA2+ channels (1)
- CA3 (1)
- CA3 pyrimidal cells (1)
- CNS cancer (1)
- Cardiovascular (1)
- Cardiovascular system (1)
- Cerebral-ischemia (1)
- Cranial window (1)
- Crespi effect (1)
- Drosophila melanogaster (1)
- ED2 (1)
- Endothelium (1)
- Endothelzelle (1)
- Fluorescence (1)
- Head-injury (1)
- Hemodynamic depression (1)
- Hemorrhage (1)
- IBA-1 (1)
- Icosanoid (1)
- In vivo imaging (1)
- In-vivo dia lysis (1)
- IntelliCage (1)
- Intravascular coagulation (1)
- Lipopolysaccharide (1)
- Lipoxin (1)
- Locus coeruleus (1)
- Mice (1)
- Microinjection (1)
- Model (1)
- Molecular-weight heparin (1)
- Mouse model (1)
- N-Acetyl-leukotriene E4 (1)
- Neurons (1)
- Neuropeptides (1)
- PAF-acether (1)
- PET (1)
- PFA in ethanol (1)
- Peptide-leukotrienes (1)
- Physiologie (1)
- Prostaglandins (1)
- R-715 (1)
- RIM-binding protein (1)
- RIM1α (1)
- Rat hippocampus (1)
- Rats (1)
- Renal circulation (1)
- SV pool (1)
- Silver degeneration staining (1)
- Supraoptic nucleus (1)
- Sympathetic nervous system (1)
- T-2 toxin (1)
- TBI (1)
- TNF-α (1)
- TSPO (1)
- Thromboplastin (1)
- Thrombus formation (1)
- Thyreotropin-Releasinghormon (1)
- Trauma (1)
- Vasopressin (1)
- Ventilation (1)
- Von Willebrand factor (1)
- Willebrand-Faktor (1)
- Zell-Adhäsionsmolekül (1)
- [3H][3Me-His2]-TRH (1)
- acute brain slices (1)
- astrocytes (1)
- autoradiography (1)
- benzodiazepine antagonist. (1)
- blastocysts (1)
- blood-brain barrier (1)
- brain (1)
- brain development (1)
- brain edema (1)
- cancer (1)
- catecholamlnes (1)
- chlorisondamine (1)
- compaction (1)
- dSTORM (1)
- damage control orthopedics (1)
- dennorphin (1)
- derivation (1)
- dermorphin (1)
- differentiation (1)
- diffuse (1)
- edema (1)
- electron tomography (1)
- factor XII (1)
- femoral fracture (1)
- flumazenil (1)
- focal (1)
- focal brain lesion (1)
- hemorrhagic shock (1)
- high-pressure freezing (1)
- high-pressure freezing/freeze substitution (1)
- hippocampal (1)
- hippocampal mossy fiber bouton (1)
- homeostasis (1)
- hypovolemic hypotension (1)
- immunofluorescence (1)
- immunohistochemistry (1)
- in-vitro (1)
- in-vivo (1)
- kinin receptors (1)
- lines (1)
- locus coeruleus (1)
- metabolism (1)
- methylation (1)
- mice (1)
- mortality (1)
- mossy fiber synapses (1)
- mycotoxin (1)
- naloxonazine (1)
- naloxone (1)
- nanotopology (1)
- neuroinflammation (1)
- neuromuscular junction (1)
- neuroprotection (1)
- object recognition memory (1)
- opiates (1)
- opioid peptides (1)
- opioid receptors (1)
- opioid-benzodiazepine interactions (1)
- paediatric cancer (1)
- plasticity (1)
- platelet-activating factor (1)
- platform (1)
- pluripotent (1)
- presynaptic (1)
- presynaptic plasticity (1)
- prostacyclins (1)
- proteins (1)
- rat (1)
- regional blood flow (1)
- regional blood ftow (1)
- release (1)
- renin (1)
- respiration (1)
- reveals (1)
- shock (1)
- specification (1)
- stress (1)
- subarachnoid hemorrhage (SAH) (1)
- super-resolution microscopy (1)
- sympathetic nerve activity. (1)
- synaptic ultrastructure (1)
- therapy (1)
- thromboinflammation (1)
- thrombosis (1)
- total peripheral resistance (1)
- tumor necrosis factor (1)
- vasopressin (1)
- weight drop (1)
- µ opioid receptors (1)
- µ·Opioid receptor subtypes (1)
- β-APP (1)
Institute
- Neurochirurgische Klinik und Poliklinik (73) (remove)
Background:
Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in the plasma is triggered by activated factor XII. Hence, we set out to study in detail the influence of activated factor XII on the abovementioned pathophysiological features of TBI.
Methods:
Using a cortical cryogenic lesion model in mice, we investigated the impact of genetic deficiency of factor XII and inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused Infestin-4 on the release of bradykinin, the brain lesion size, and contact-kinin system-dependent pathological events. We determined protein levels of bradykinin, intracellular adhesion molecule-1, CC-chemokine ligand 2, and interleukin-1β by enzyme-linked immunosorbent assays and mRNA levels of genes related to inflammation by quantitative real-time PCR. Brain lesion size was determined by tetrazolium chloride staining. Furthermore, protein levels of the tight junction protein occludin, integrity of the blood-brain barrier, and brain water content were assessed by Western blot analysis, extravasated Evans Blue dye, and the wet weight-dry weight method, respectively. Infiltration of neutrophils and microglia/activated macrophages into the injured brain lesions was quantified by immunohistological stainings.
Results:
We show that both genetic deficiency of factor XII and inhibition of activated factor XII in mice diminish brain injury-induced bradykinin release by the contact-kinin system and minimize brain lesion size, blood-brain barrier leakage, brain edema formation, and inflammation in our brain injury model.
Conclusions:
Stimulation of bradykinin release by activated factor XII probably plays a prominent role in expanding secondary brain damage by promoting brain edema formation and inflammation. Pharmacological blocking of activated factor XII could be a useful therapeutic principle in the treatment of TBI-associated pathologic processes by alleviating posttraumatic inflammation and brain edema formation.
Neurotransmitter release is stabilized by homeostatic plasticity. Presynaptic homeostatic potentiation (PHP) operates on timescales ranging from minute- to life-long adaptations and likely involves reorganization of presynaptic active zones (AZs). At Drosophila melanogaster neuromuscular junctions, earlier work ascribed AZ enlargement by incorporating more Bruchpilot (Brp) scaffold protein a role in PHP. We use localization microscopy (direct stochastic optical reconstruction microscopy [dSTORM]) and hierarchical density-based spatial clustering of applications with noise (HDBSCAN) to study AZ plasticity during PHP at the synaptic mesoscale. We find compaction of individual AZs in acute philanthotoxin-induced and chronic genetically induced PHP but unchanged copy numbers of AZ proteins. Compaction even occurs at the level of Brp subclusters, which move toward AZ centers, and in Rab3 interacting molecule (RIM)-binding protein (RBP) subclusters. Furthermore, correlative confocal and dSTORM imaging reveals how AZ compaction in PHP translates into apparent increases in AZ area and Brp protein content, as implied earlier.
Revealing the molecular organization of anatomically precisely defined brain regions is necessary for refined understanding of synaptic plasticity. Although three-dimensional (3D) single-molecule localization microscopy can provide the required resolution, imaging more than a few micrometers deep into tissue remains challenging. To quantify presynaptic active zones (AZ) of entire, large, conditional detonator hippocampal mossy fiber (MF) boutons with diameters as large as 10 mu m, we developed a method for targeted volumetric direct stochastic optical reconstruction microscopy (dSTORM). An optimized protocol for fast repeated axial scanning and efficient sequential labeling of the AZ scaffold Bassoon and membrane bound GFP with Alexa Fluor 647 enabled 3D-dSTORM imaging of 25 mu m thick mouse brain sections and assignment of AZs to specific neuronal substructures. Quantitative data analysis revealed large differences in Bassoon cluster size and density for distinct hippocampal regions with largest clusters in MF boutons. Pauli et al. develop targeted volumetric dSTORM in order to image large hippocampal mossy fiber boutons (MFBs) in brain slices. They can identify synaptic targets of individual MFBs and measured size and density of Bassoon clusters within individual untruncated MFBs at nanoscopic resolution.