@article{HoppAlbertWeissenbergerMencletal.2016,
  author    = {Hopp, Sarah and Albert-Weissenberger, Christiane and Mencl, Stine and Bieber, Michael and Schuhmann, Michael K. and Stetter, Christian and Nieswandt, Bernhard and Schmidt, Peter M. and Monoranu, Camelia-Maria and Alafuzoff, Irina and Marklund, Niklas and Nolte, Marc W. and Sir{\´e}n, Anna-Leena and Kleinschnitz, Christoph},
  title     = {Targeting coagulation factor XII as a novel therapeutic option in brain trauma},
  series = {Annals of Neurology},
  volume    = {79},
  journal   = {Annals of Neurology},
  number    = {6},
  doi       = {10.1002/ana.24655},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188800},
  pages     = {970-982},
  year      = {2016},
  abstract  = {Objective: Traumatic brain injury is a major global public health problem for which specific therapeutic interventions are lacking. There is, therefore, a pressing need to identify innovative pathomechanism-based effective therapies for this condition. Thrombus formation in the cerebral microcirculation has been proposed to contribute to secondary brain damage by causing pericontusional ischemia, but previous studies have failed to harness this finding for therapeutic use. The aim of this study was to obtain preclinical evidence supporting the hypothesis that targeting factor XII prevents thrombus formation and has a beneficial effect on outcome after traumatic brain injury. Methods: We investigated the impact of genetic deficiency of factor XII and acute inhibition of activated factor XII with a single bolus injection of recombinant human albumin-fused infestin-4 (rHA-Infestin-4) on trauma-induced microvascular thrombus formation and the subsequent outcome in 2 mouse models of traumatic brain injury. Results: Our study showed that both genetic deficiency of factor XII and an inhibition of activated factor XII in mice minimize trauma-induced microvascular thrombus formation and improve outcome, as reflected by better motor function, reduced brain lesion volume, and diminished neurodegeneration. Administration of human factor XII in factor XII-deficient mice fully restored injury-induced microvascular thrombus formation and brain damage. Interpretation: The robust protective effect of rHA-Infestin-4 points to a novel treatment option that can decrease ischemic injury after traumatic brain injury without increasing bleeding tendencies.},
  language  = {en}
}
@article{IsraelOhsiekAlMomanietal.2016,
  author    = {Israel, Ina and Ohsiek, Andrea and Al-Momani, Ehab and Albert-Weissenberger, Christiane and Stetter, Christian and Mencl, Stine and Buck, Andreas K. and Kleinschnitz, Christoph and Samnick, Samuel and Sir{\´e}n, Anna-Leena},
  title     = {Combined [\(^{18}\)F]DPA-714 micro-positron emission tomography and autoradiography imaging of microglia activation after closed head injury in mice},
  series = {Journal of Neuroinflammation},
  volume    = {13},
  journal   = {Journal of Neuroinflammation},
  number    = {140},
  doi       = {10.1186/s12974-016-0604-9},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-146606},
  year      = {2016},
  abstract  = {Background Traumatic brain injury (TBI) is a major cause of death and disability. Neuroinflammation contributes to acute damage after TBI and modulates long-term evolution of degenerative and regenerative responses to injury. The aim of the present study was to evaluate the relationship of microglia activation to trauma severity, brain energy metabolism, and cellular reactions to injury in a mouse closed head injury model using combined in vivo PET imaging, ex vivo autoradiography, and immunohistochemistry. Methods A weight-drop closed head injury model was used to produce a mixed diffuse and focal TBI or a purely diffuse mild TBI (mTBI) in C57BL6 mice. Lesion severity was determined by evaluating histological damage and functional outcome using a standardized neuroscore (NSS), gliosis, and axonal injury by immunohistochemistry. Repeated intra-individual in vivo μPET imaging with the specific 18-kDa translocator protein (TSPO) radioligand [\(^{18}\)F]DPA-714 was performed on day 1, 7, and 16 and [\(^{18}\)F]FDG-μPET imaging for energy metabolism on days 2-5 after trauma using freshly synthesized radiotracers. Immediately after [\(^{18}\)F]DPA-714-μPET imaging on days 7 and 16, cellular identity of the [\(^{18}\)F]DPA-714 uptake was confirmed by exposing freshly cut cryosections to film autoradiography and successive immunostaining with antibodies against the microglia/macrophage marker IBA-1. Results Functional outcome correlated with focal brain lesions, gliosis, and axonal injury. [\(^{18}\)F]DPA-714-μPET showed increased radiotracer uptake in focal brain lesions on days 7 and 16 after TBI and correlated with reduced cerebral [\(^{18}\)F]FDG uptake on days 2-5, with functional outcome and number of IBA-1 positive cells on day 7. In autoradiography, [\(^{18}\)F]DPA-714 uptake co-localized with areas of IBA1-positive staining and correlated strongly with both NSS and the number of IBA1-positive cells, gliosis, and axonal injury. After mTBI, numbers of IBA-1 positive cells with microglial morphology increased in both brain hemispheres; however, uptake of [\(^{18}\)F]DPA-714 was not increased in autoradiography or in μPET imaging. Conclusions [\(^{18}\)F]DPA-714 uptake in μPET/autoradiography correlates with trauma severity, brain metabolic deficits, and microglia activation after closed head TBI.},
  language  = {en}
}
@article{AlbertWeissenbergerSiren2010,
  author    = {Albert-Weissenberger, Christiane and Sir{\´e}n, Anna-Leena},
  title     = {Experimental traumatic brain injury},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68131},
  year      = {2010},
  abstract  = {Traumatic brain injury, a leading cause of death and disability, is a result of an outside force causing mechanical disruption of brain tissue and delayed pathogenic events which collectively exacerbate the injury. These pathogenic injury processes are poorly understood and accordingly no effective neuroprotective treatment is available so far. Experimental models are essential for further clarification of the highly complex pathology of traumatic brain injury towards the development of novel treatments. Among the rodent models of traumatic brain injury the most commonly used are the weight-drop, the fluid percussion, and the cortical contusion injury models. As the entire spectrum of events that might occur in traumatic brain injury cannot be covered by one single rodent model, the design and choice of a specific model represents a major challenge for neuroscientists. This review summarizes and evaluates the strengths and weaknesses of the currently available rodent models for traumatic brain injury.},
  subject      = {Trauma},
  language  = {en}
}
@article{EimerlSirenFeuerstein1986,
  author    = {Eimerl, J. and Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Systemic and regional hemodynamic effects of leukotrienes D\(_4\) and E\(_4\) in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63317},
  year      = {1986},
  abstract  = {No abstract available},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{Siren1982,
  author    = {Sir{\´e}n, Anna-Leena},
  title     = {Differences in central actions of arachidonic acid and prostaglandin F\(_{2\alpha}\) between spontaneously hypertensive and normotensive rats},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63324},
  year      = {1982},
  abstract  = {Prostag1andin F\(_{2\alpha}\) (PGF\(_{2\alpha}\)) is one of the most common metabo1ites of arachidonic acid (M) in rat brain. When administered intracerebroventricularly (i.c.v.) to rats, both AA and PGFal exert dose-related hypertensive, tachycardic and hyperthermic effects. Metabolie alterations in the endogenaus formation of some prostaglandins in the brain-stem of spontaneously hypertensive rats (SHR) have been reported. Therefore the central effects of AA and PGF \(_{2\alpha}\) on blood pressure, heart rate and body temperature were studied both in SHR and nonootensive Wistar rats (NR) under urethane-anaesthesia. The hypertensive effect of AA i.c.v. (0.01-100 \(\mu\)g/rat) was larger in magni tude in SHR than in NR, but there was no significant difference in the M-induced changes of heart rate and body temperature between the groups. Pretreatment of NR wi th soditm1 :meclofenamate (1 mg/rat i.c.v.) antagonised the central effects of M indicating that these effects are not due to M itself but to its conversion to prostaglandins. Unlike the effects of AA, the central hypertensive, tachycardic and hyperthennic responses to PGF\(_{2\alpha}\) (0.5-50 l-lg/rat i.c.v .) were significantly attenuated in SHR. The present results obtained with M are conpatible with the previous assumption that the synthesis of prostaglandins in the brain of SHR might differ from that in NR. The results also demonstrate that the central effects of PGF\(_{2\alpha}\) are reduced in SHR.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1989,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Effect of PAF and BN 52021 on cardiac function and regional blood flow in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63145},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1989,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Thyrotropin releasing hormone-induced hindquarter vasodilation is mediated by \(\beta _2\)-adrenoceptors},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63155},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1989,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Hemodynamic effects of endothelin after systemic and central nervous System administration in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63165},
  year      = {1989},
  abstract  = {No abstract available},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{FeuersteinLettsSiren1988,
  author    = {Feuerstein, G. and Letts, G. and Sir{\´e}n, Anna-Leena},
  title     = {N-Ac-Leukotriene E\(_4\): Unique vascular activity in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63171},
  year      = {1988},
  abstract  = {No abstract available},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenLakeFeuerstein1988,
  author    = {Sir{\´e}n, Anna-Leena and Lake, C. R. and Feuerstein, G.},
  title     = {Hemodynamic and neural mechanisms of action of thyrotropin releasing hormone in the rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63183},
  year      = {1988},
  abstract  = {Tbe mechanisms mediating the etl'ects ofthyrotropin-releasing hormone (TRH) on the cardiovascular system were studied in the conscious rat. Intracerebroventricolar (i.c. v.) injection of TRH (8 pmol-80 nmollkg) induced dose-dependent lncreases in mean arterial pressure, heart rate, and cardiac index. Rindquarter blood Oow increased due to vasodilation, while an lncrease in renal and mesenteric vascular resistance caused a decrease in blood Oow in the respective organs. The plasma Ievels of norepinephrine a~d epinephrine were increased by TRH, while there was no change in plasma renin activity or vasopressin. Tbe cardiovascular actions of i.c. v. TRH were not in.fluenced by blockade of the renin-angiotensin system or vasopressin receptors. Tbe ganglion blocker chlorisondamine and the a 1- aod al-adrenoreceptor antagooist phentolamlne (2 mg/kg i.v.) abolished the increase in blood pressure and mesenteric vasoconstriction after i.c. v. TRH. Propranolol (2 mg/kg i. v.) blocked the TRH-ioduced increase in cardiac index, heart rate, and hindquarter blood flow. The hindquarter vasodllatlon lnduced by TRH was also blocked by the selective ß1-adrenocept9r antagonist ICI 188,551 (1 or 2 mg/kg i.v.), while tbe ,8,-adrenoceptor blocker practolol (10 mg/kg i.v.) had no eft'ect on the hindquarter vasodiJation produced by TRH but totally blocked the increase in cardiac Index. In adrenal demedullated rats, the systemic hemodynamic eft'ects ofi.c. v. TRH were dimlnished along with the decrease in renal blood flow and lncrease in renal vascular resistance; however, the iocrease in hfndquarter blood flow was attenuated only in adrenal demedullated rats pretreated with the sympathetlc blocker bretylium. The renal vasoconstriction induced by i.c. v. TRH was not abolished by renal denervation. In sinoaortic debufl'ered rats, the pressor, tachycardic, and mesenteric vasoconstrictor responses to centrally administered TRH were significantly potentiated. Taken together, these data soggest that the putative rieurotransmitter TRH may play a role in central regulation of cardiac functions and organ blood flow distribution through both tbe sympathetic nerves and the adrenal medulla. A pivotal roJe for ß1-adrenoceptors in mediation ofhindquarter vasodilation ls also demonstrated.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenLettsFeuerstein1988,
  author    = {Sir{\´e}n, Anna-Leena and Letts, G. and Feuerstein, G.},
  title     = {N-Acetyl-leukotriene E\(_4\) is a potent constrictor of rat mesenteric vessels},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63196},
  year      = {1988},
  abstract  = {N-Acetyl-leukotriene E\(_4\) administered to conscious freely moving rats produced a dose-dependent vasoconstriction in the mesenteric vessels which led to profound reduction of blood flow to the gut. Renal and hindquarter blood flow and vascular resistance were not affected even by high doses of N-acetyl-leukotriene E\(_4\) . N-Acetyl-leukotriene E\(_4\) was 10-fold more potent than the thromboxane analog U-46619 and 1000-fold more potent than prostaglandin F\(_{2a}\) but 2-5-fold less potent than leukotriene D\(_4\)/E\(_4\) to induce mesenteric vasoconstriction. These data indicatc that N-acetylleukotriene E\(_4\) is a biologically active metabolite of peptide leukotrienes, and might play a role in cardiovascular derangements mediated by leukotrienes.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{FeuersteinSiren1988,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Mesenteric vascular responses to i.v. administration of lipoxin A\(_4\) and lipoxin B\(_4\) in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63200},
  year      = {1988},
  abstract  = {Lipoxin A (LXA\(_4\)) and lipoxin B\(_4\)(LXB\(_4\)) are newly discovered lipoxygenase-interacting products of leukocytes which might have a role in cardiovascular events associated with anaphylaxis. We have tested this possibility by systemic administration of both LXA\(_4\) and LXB\(_4\) to the conscious rat while monitaring systemic and regional hemodynamic changes. LXA\(_4\) and' LXB\(_4\) (l-100 pg/kg) produced dose-dependent constriction of the mesenteric vessels, up to + 123±23\% and +50±9\% for LXA\(_4\)/B\(_4\) , respectively. Dose-related changes were not observed in arterial blood pressure, heart rate, renal (LXB\(_4\)) and hindquarter blood ftow. We suggest that LXA\(_4\) and LXB\(_4\) might affect selective vascular beds, such as the mesenteric vessels, and contribute to variations in blood flow in specific pathophysiological states.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{Siren1988,
  author    = {Sir{\´e}n, Anna-Leena},
  title     = {Cardiovascular pharmacology of thyrotropin releasing hormone},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63214},
  year      = {1988},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{FeuersteinSiren1988,
  author    = {Feuerstein, G. and Sir{\´e}n, Anna-Leena},
  title     = {Hypothalamic µ-receptors in the cardiovascular control: a review},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63228},
  year      = {1988},
  abstract  = {The endogenous opioid system includes three major families of peptides [22): dynorphins (derived from pre-proenkephalin B); endorphins (derived from pre-proopiomelanocortin) and enkephalins (derived from pre-proenkephalin A). Multiple species of opioid peptides are derived from these major precursors and many of them possess potent cardiovascular properties. Multiple forms of opioid receptors have been defined in the central nervous system. Although the relationship of these receptors to the multiple actions of the opioid systems is not weil understood, some predications can be made: in vitro the dynorphin-related peptidesbind preferentially to kappa-opioid receptors; the enkephalins bind preferentially to delta and JL-opioid receptors and while beta-endorphin binds to mu- and delta-, but not to kappa-opioid receptors. While littleis known on the roJe ofthe opioid system in normal cardiovascular regulation, it has become clear that cardiovascular stress situations substantially modify the activity ofthe endogenous opioid system. This review focuses on the mu-opioid system in the hypothalamus with special emphasis on its potential roJe in cardiovascular control of both normal and pathophysiologic states.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1988,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Cardiovascular effects of rat calcitonin gene-related peptide in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63236},
  year      = {1988},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{FeuersteinLeaderSirenetal.1987,
  author    = {Feuerstein, G. and Leader, P. and Sir{\´e}n, Anna-Leena and Braquet, P.},
  title     = {Protective effect of PAF-acether antagonist, BN 52021, in trichothecen toxicosis},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63244},
  year      = {1987},
  abstract  = {Trichothecenes are mycotoxins which produce Iethai toxicosis in humans and animals, yet no adequate therapeutic regimen has been developed. This study provides evidence that the selective platelet activating factor (PAF) antagonist, BN 52021 (5-15 mg/kg i.v.) can prolong the survival of conscious rats exposed to a highly Iethai T -2 toxicosis. These data also suggest that P AF is an important mediator of this unique toxicosis.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{LabrooCohenLozovskyetal.1987,
  author    = {Labroo, V. M. and Cohen, L. A. and Lozovsky, D. and Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Dissociation of the cardiovascular and prolactin-releasing activities of TRH by histidine replacement},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63253},
  year      = {1987},
  abstract  = {No abstract available},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{PaakkariNurminenSiren1986,
  author    = {Paakkari, I. and Nurminen, M-L. and Sir{\´e}n, Anna-Leena},
  title     = {Cardioventilatory effects of TRH in anesthetized rats: role of the brainstem},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63277},
  year      = {1986},
  abstract  = {Cardioventilator responses were studied in anaesthetized rats after injections of TRH into either the lateral (i.c.v. lat) or the fourth (i.c.v. IV) cerebral ventricles. TRH induced a morerapid hypertensive effect i.c.v. IV than i.c.v. lat. Blocking of the cerebral aqueduct abolished the hypertensive and tachypnoeic effects of TRH i.c.v. lat but not those of TRH i.c.v. IV. It is concluded that TRH increased blood pressure and ventilation rate via brain stem structures close to the fourtli ventricle.},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenPowellFeuerstein1986,
  author    = {Sir{\´e}n, Anna-Leena and Powell, E. and Feuerstein, G.},
  title     = {Thyrotropin releasing hormone in hypovolemia: a hemodynamic evaluation in the rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63288},
  year      = {1986},
  abstract  = {ln the present study the effects of thyrotropin releasing hormone (TRH) and its stable analogue, CG3703, on cardiac output (thermodilution, Cardiomax) and regional blood flow (BF; directional pulsed Doppler technique) were investigated in hypovolemic hypotension in the rat. In urethan-anesthetized rats TRH (0.5 or 2 mg/ kg ia) or CG3703 (0.05 or 0.5 mg/kg ia) reversed the bleeding (27\% of the blood volume)-induced decreases in mean arterial ...},
  subject      = {Neurobiologie},
  language  = {en}
}
@article{SirenFeuerstein1986,
  author    = {Sir{\´e}n, Anna-Leena and Feuerstein, G.},
  title     = {Effect of T-2 toxin on regional blood flow and vascular resistance in the conscious rat},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63293},
  year      = {1986},
  abstract  = {The acute effect ofT-2 toxemia on local blood flow and vascular resistance in hindquarter. mesenteric. and renal vascular beds was continuously measured by the directional pulsed Doppler technique in conscious, male Sprague-Dawley rats. Intravenous injection ofT-2 toxin (I mg/kg) in the conscious rat reduced blood flow and increased vascular resistance in all blood vessels studied but had no significant effect on mean arterial pressure or heart rate. The blood flow in hindquarters gradually decreased to a minimum of -77 ± 9\% (mean ±SE) 6 hr after the toxin injection. The hindquarter vascular resistance concomitantly increased to a maximum value of + 323 ± 69\% above thc resistance before toxin administration. Mesenteric and renal blood flow initially increased (slightly) and then gradually decreased. The maximum drop of blood flow, -90 ± 13\% and -76 ± 13\% for the mesenteric and renal vascular beds, respectively, was achieved 4 hr after T-2 toxin injection and the blood flow values remained low for up to 6 hr. Simultaneously with the impairment of},
  subject      = {Neurobiologie},
  language  = {en}
}