@article{AdeyemoShapiraTombaccinietal.1991, author = {Adeyemo, O. M. and Shapira, S. and Tombaccini, D. and Pollard, H. and Feuerstein, G. and Sir{\´e}n, Anna-Leena}, title = {A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63087}, year = {1991}, abstract = {A Goldfish Model for Evaluation of the Neurotaxicity of \(\omega\)-Conotoxin GVI A and Screening of Monoclonal Antibodies. ADEYEMO, 0. M .. SHAPIRA, S., TOMBACCINI, D., POLLARD, H. 8 .• FEUERSTEIN, G .. AND SIREN, A-L. ( 1991 ). Toxicol. App/. Pharmaco/. 108, 489-496. The neurotoxicity of \(\omega\)-conotoxin (\(\omega\)-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. \(\omega\)-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. \(\omega\)CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antiborlies was investigated in vivo by either ( l) preincubation of the antibody with w-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before \(\omega\)CgTx injection in a 10:1 antibody/\(\omega\)-CgTx molar ratio. The LD50 dose of \(\omega\)-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with \(\omega\)-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality. ASB, and toxicity time. The antitoxin activity of the monoclonal antiborlies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by \(\omega\)-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.0 l, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple. accurate, and inexpensive in vivo model for the study of the toxicity of \(\omega\)CgTx}, subject = {Neurobiologie}, language = {en} } @article{MrestaniPauliKollmannsbergeretal.2021, author = {Mrestani, Achmed and Pauli, Martin and Kollmannsberger, Philip and Repp, Felix and Kittel, Robert J. and Eilers, Jens and Doose, S{\"o}ren and Sauer, Markus and Sir{\´e}n, Anna-Leena and Heckmann, Manfred and Paul, Mila M.}, title = {Active zone compaction correlates with presynaptic homeostatic potentiation}, series = {Cell Reports}, volume = {37}, journal = {Cell Reports}, number = {1}, doi = {10.1016/j.celrep.2021.109770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265497}, pages = {109770}, year = {2021}, abstract = {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.}, language = {en} } @article{McCarronWangSirenetal.1994, author = {McCarron, R. M. and Wang, L. and Sir{\´e}n, Anna-Leena and Spatz, M. and Hallenbeck, J. M.}, title = {Adhesion molecules on normotensive and hypertensive rat brain endothelial cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-86819}, year = {1994}, abstract = {The intercellular adhesion of circulating leukocytes to vascular endothellum ls a prerequisite for leukocyte emigration from the blood to extravascular tlssues. This process is facllltated by adhesion molecules on the surfaces of both the vascular endothelial cells and the leukocytes. The experiments presented here demonstrate for the first time that the leukocyte adhesion receptor, intercellular adhesion molecule-1, is constitutively expressed on cultured cerebromicrovascular endothelial cell lines derived from both spontaneously hypertensive (SHR) rats and normotensive WistarKyoto (WKY) rats. Both cultures contained simliar numbers of cells constitutively expressing this adhesion molecule (31.4\% and 29.6\%, respectlvely). Adhesion molecule expression was up-regulated by interleukin-1 ß, tumor necrosis factor-a, interferon-y and lipopolysaccharide in a dose- and time-dependent manner. Both cultures exhibited similar maximum levels of adhesion molecule up-regulation to optimal concentrations of all three cytokines. However, SHR endothelial cells were moresensitive to all three cytokines; significantly higher levels of intercellular adhesion molecule-1 expresslon were seen on SHR as opposed to WKY endothelial cells cultured with sub-optimal cytokine concentrations. It was also observed that lipopolysaccharide up-regulated intercellular adhesion molecule-1 expression on SHR endothelial cells to a greater extent than on WKY endothelial cells. The findings that intercellular adhesion molecule-1 can be up-regulated to a greater degree on SHR endothelial cells may have important implications for in vivo perivascular leukocyte accumulation under hypertensive conditions. These observations indicate a possible mechanism by which hypertension may predispose to the development of disorders such as atherosclerosis and stroke.}, subject = {Endothelzelle}, language = {en} } @techreport{McCarronDoronSirenetal.1994, author = {McCarron, R. M. and Doron, D. A. and Sir{\´e}n, Anna-Leena and Feuerstein, G. Z. and Heldman, E. and Pollard, H. B. and Spatz, M. and Hallenbeck, J. M.}, title = {Agonist-stimulated release of von Willebrand factor and procoagulant factor VIII in rats with and without risk factors for stroke [Research Report]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62945}, year = {1994}, abstract = {Lipopolysaccharidc (LPS)-induced (i.v. or i.c.v., 1.8 mg/kg) release of von Willebrand factor (vWF) ·was examined in spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats. SHR rats releascd significantly (P < 0.05) more vWF than WKY rats in response to LPS. LPS also inhibited factor VIII procoagulant activity (FVIII: c) which may indicate an increase in thrombin activity. Cultured cerebrovascular endothelial cells (EC) derived from both SHR and WKY rats, as weil as human umbilical vein EC (HUVEC) cultures constitutively released vWF. Treatment with agonists including LPS, thrombin and tumor necrosis factor-a (TNFa) did not affect the in vitro secretion of vWF by cerebrovascular EC cultures but significantly upregulated vWF release by HUVEC cultur~s. Preincubation of cerebrovascular EC cultures with interleukin-1 OL-l) ± TNFa or co-culturing in the presence of LPS-activated syngeneic monocytes had no effect on vWF secretion. The findings demoostrate that conditions of hypertension may affect endothelial cells and make them more responsive to agonist Stimulation and thereby increase secretion of vWF, an important factqr in hemostasis as weil as thrombosis. The capacity of LPS to significantly affect the in vivo secretion of vWF in SHR and WKY rats but not cultured cerebrovascular EC indicates that observed elevations in plasma vWF were not derived from cerebrovascular EC. lt is suggested that hypertension may function as a risk factor for thrombotic stroke by influencing factors involved in coagulation processes, such as vWF and factor VIII : c.}, subject = {Neurobiologie}, language = {en} } @article{HoppNolteStetteretal.2017, author = {Hopp, Sarah and Nolte, Marc W. and Stetter, Christian and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena and Albert-Weissenberger, Christiane}, title = {Alleviation of secondary brain injury, posttraumatic inflammation, and brain edema formation by inhibition of factor XIIa}, series = {Journal of Neuroinflammation}, volume = {14}, journal = {Journal of Neuroinflammation}, number = {39}, doi = {10.1186/s12974-017-0815-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157490}, year = {2017}, abstract = {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.}, language = {en} } @article{StetterLopezCaperuchipiHoppKraemeretal.2021, author = {Stetter, Christian and Lopez-Caperuchipi, Simon and Hopp-Kr{\"a}mer, Sarah and Bieber, Michael and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena and Albert-Weißenberger, Christiane}, title = {Amelioration of cognitive and behavioral deficits after traumatic brain injury in coagulation factor XII deficient mice}, series = {International Journal of Molecular Sciences}, volume = {22}, journal = {International Journal of Molecular Sciences}, number = {9}, issn = {1422-0067}, doi = {10.3390/ijms22094855}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284959}, year = {2021}, abstract = {Based on recent findings that show that depletion of factor XII (FXII) leads to better posttraumatic neurological recovery, we studied the effect of FXII-deficiency on post-traumatic cognitive and behavioral outcomes in female and male mice. In agreement with our previous findings, neurological deficits on day 7 after weight-drop traumatic brain injury (TBI) were significantly reduced in FXII\(^{-/-}\) mice compared to wild type (WT) mice. Also, glycoprotein Ib (GPIb)-positive platelet aggregates were more frequent in brain microvasculature of WT than FXII\(^{-/-}\) mice 3 months after TBI. Six weeks after TBI, memory for novel object was significantly reduced in both female and male WT but not in FXII\(^{-/-}\) mice compared to sham-operated mice. In the setting of automated home-cage monitoring of socially housed mice in IntelliCages, female WT mice but not FXII\(^{-/-}\) mice showed decreased exploration and reacted negatively to reward extinction one month after TBI. Since neuroendocrine stress after TBI might contribute to trauma-induced cognitive dysfunction and negative emotional contrast reactions, we measured peripheral corticosterone levels and the ration of heart, lung, and spleen weight to bodyweight. Three months after TBI, plasma corticosterone levels were significantly suppressed in both female and male WT but not in FXII\(^{-/-}\) mice, while the relative heart weight increased in males but not in females of both phenotypes when compared to sham-operated mice. Our results indicate that FXII deficiency is associated with efficient post-traumatic behavioral and neuroendocrine recovery.}, language = {en} } @article{SirenStetterHirschbergetal.2013, author = {Sir{\´e}n, Anna-Leena and Stetter, Christian and Hirschberg, Markus and Nieswandt, Bernhard and Ernestus, Ralf-Ingo and Heckmann, Manfred}, title = {An experimental protocol for in vivo imaging of neuronal structural plasticity with 2-photon microscopy in mice}, series = {Experimental \& Translational Stroke Medicine}, journal = {Experimental \& Translational Stroke Medicine}, doi = {10.1186/2040-7378-5-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96908}, year = {2013}, abstract = {Introduction Structural plasticity with synapse formation and elimination is a key component of memory capacity and may be critical for functional recovery after brain injury. Here we describe in detail two surgical techniques to create a cranial window in mice and show crucial points in the procedure for long-term repeated in vivo imaging of synaptic structural plasticity in the mouse neocortex. Methods Transgenic Thy1-YFP(H) mice expressing yellow-fluorescent protein (YFP) in layer-5 pyramidal neurons were prepared under anesthesia for in vivo imaging of dendritic spines in the parietal cortex either with an open-skull glass or thinned skull window. After a recovery period of 14 days, imaging sessions of 45-60 min in duration were started under fluothane anesthesia. To reduce respiration-induced movement artifacts, the skull was glued to a stainless steel plate fixed to metal base. The animals were set under a two-photon microscope with multifocal scanhead splitter (TriMScope, LaVision BioTec) and the Ti-sapphire laser was tuned to the optimal excitation wavelength for YFP (890 nm). Images were acquired by using a 20×, 0.95 NA, water-immersion objective (Olympus) in imaging depth of 100-200 μm from the pial surface. Two-dimensional projections of three-dimensional image stacks containing dendritic segments of interest were saved for further analysis. At the end of the last imaging session, the mice were decapitated and the brains removed for histological analysis. Results Repeated in vivo imaging of dendritic spines of the layer-5 pyramidal neurons was successful using both open-skull glass and thinned skull windows. Both window techniques were associated with low phototoxicity after repeated sessions of imaging. Conclusions Repeated imaging of dendritic spines in vivo allows monitoring of long-term structural dynamics of synapses. When carefully controlled for influence of repeated anesthesia and phototoxicity, the method will be suitable to study changes in synaptic structural plasticity after brain injury.}, language = {en} } @article{AlbertWeissenbergerVarrallyayRaslanetal.2012, author = {Albert-Weißenberger, Christiane and V{\´a}rrallyay, Csan{\´a}d and Raslan, Furat and Kleinschnitz, Christoph and Sir{\´e}n, Anna-Leena}, title = {An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-75368}, year = {2012}, abstract = {Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.}, subject = {Medizin}, language = {en} } @article{ShuaibXuCrainetal.1990, author = {Shuaib, A. and Xu, K. and Crain, B. and Sir{\´e}n, Anna-Leena and Feuerstein, Giora and Hallenbeck, J. and Davis, JN}, title = {Assessment of damage from implantation of microdialysis probes in the rat hippocampus with silver degeneration staining}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47433}, year = {1990}, abstract = {We used a sensitive silver degeneration staining method to study the effects of insertion of microdialysis probes in rat dorsal hippocampus and neocortex. Nine animals were sacrificed 24 h, 3 days or 7 days after implantation of dialysis tubing. Although mild neuronal cell death and small petechial hemorrhages were seen in elose proximity to the implantation site, the striking finding was the presence of degenerating axons both adjacent to the implantation site and in remote sites such as the corpus callosum and contralateral hippocampus. The observed changes could alter brain function near or remote from the implantation site and should be considered in analysis of dialysis experiments.}, subject = {Neurophysiologie}, language = {en} } @article{LankiewiczBowersReynoldsetal.1992, author = {Lankiewicz, Leszek and Bowers, Cyril Y. and Reynolds, G. A. and Labroo, Virender and Cohen, Louis A. and Vonhof, Stefan and Sir{\´e}n, Anna-Leena and Spatola, Arno F.}, title = {Biological Activities of Thionated Thyrotropin-Releasing Hormone Analogs}, series = {Biochemical and Biophysical Research Communications}, volume = {184}, journal = {Biochemical and Biophysical Research Communications}, number = {1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128152}, pages = {359-366}, year = {1992}, abstract = {No abstract available.}, language = {en} }