Fetal Brain Development and Disease Programming
AG Fetale Hirnentwicklung und Programmierung von Krankheiten
(Homepage)
Leiter
Mitarbeiter
- Dipl. Biologin Iwa Antonow-Schlorke
- Dr. med. Christoph Bergmeier
- Dr. med. Sven Rupprecht
- Dr. med. Rene Schiffner
- Dr. med. Florian Rakers
- Claudia Sommer
Institut für Versuchstierkunde und Tierschutz
- Dr. Harald Schubert IVuT
Tel.: 03641 - 9 372 01 - Dr. med. vet. Sabine Bischoff
Tel.: 03641 - 9 372 01
Forschungsschwerpunkte
- Die fetale Reifung der Hirnfunktion und deren Beeinflussung durch Glukokortikoide, Stress und Mangelernährung
- Zerebrale Verarbeitung von Geräuschen und Vibrationen durch den Feten in utero und deren Bedeutung für die Hirnentwicklung
- Mechanismen der fetalen Programmierung von kardio- und zerebrovaskulären Erkrankungen sowie Verhaltensauffälligkeiten im späteren Leben
- Pathogenese der intrauterinen hypoxischen Hinschädigung und die Beeinflussung der Schädigung durch Glukokortikoide
- Übertragung von Protektions- und Regenerationsmechanismen bei der intrauterinen hypoxischen Hinschädigung auf den Schlaganfall im adulten Gehirn zur Erschließung neuer Therapieoptionen
Methoden
- Tiermodelle: chronisch instrumentiertes fetales Schaf und Rattenmodell
- Modelle der fetalen Fehl- und Mangelernährung, der pränatalen Glukokortikoidgabe zur Förderung der Lungenreifung sowie Hypoxiemodelle (repetitive Nabelschnurokklusion und hypoxische Hypoxie am fetalen Schaf, neonatale Hypoxie und MCAO (Fadenmodell) bei der Ratte)
- Myografie von Widerstandsgefäßen, immunhistochemische und molekularbiologische Methoden
- Standardisierte Verhaltenstests bei der Ratte
- Intrauterine Hirndurchblutungsmessung mit Mikrosphären und Laser-Doppler-Flowmetrie
- Nutzung von AEP und SEP sowie innovativer linearer und nichtlinearer EEG-Analysemethoden zur Untersuchung der Reifung komplexer neuronaler Interaktionen und der Kopplung von autonomen und kortikalen Rhythmen, Vergleichende elektrophysiologische Untersuchungen am fetalen Schafs- (EEG), Primaten- (EEG) und menschlichen Gehirn (MEG, in Kooperation mit Dr. Schleußner, Frauenklinik)
Publikationen
Original papers in peer reviewed journals
Antonow-Schlorke I.1, Schwab M.1, Cox L.A., Li C., Stuchlik K., Witte O.W., Nathanielsz P.W., McDonald T.J. (2011). Vulnerability of the fetal primate brain to moderate reduction in maternal global nutrient availability. PNAS 108(7):3011-6 (1authors contributed equally to the paper).
Schneider U., Arnscheidt C., Schwab M., Haueisen J., Seewald, H.J. Schleussner, E.(2010). Heart Steroids That Induce Lung Maturation Acutely Affect Higher Cortical Function: A Fetal Magnetoencephalography Study. Reprod Sci 16(56):509-17.
RupprechtS., Schwab M., Fitzek C., Witte O.W., Terborg C., Hagemann G. (2010). Hemispheric hypoperfusion in postictal paresis mimics early brain ischemia. Epilepsy Res 89(2-3):355-9.
Zinke J, Rupprecht S, Schwab M, Hagemann G. (2010). Nocturnal groaning (catathrenia) and epilepsy. Epileptic Disord. 12(2):136-7.
RupprechtS., Hoyer D., Hagemann G., Witte O.W., Schwab M. (2010). Central Sleep Apnea Indicates Autonomic Dysfunction in Asymptomatic Carotid Stenosis - A Potential Marker of Cardio- and Cerebrovascular Risk. Sleep 33(3):327-33.
Löhle M., Schwab M., Kadner S., Ford S., Nijland M., Lawrence P., Gilbert J., Brenna T., Nathanielsz P.W. (2009). Dose response effects of betamethasone on maturation of the fetal sheep fetal lung. Am J Obstet Gynecol 202(2):186.e1-7.
Frasch M.G., Müller T., Szynkaruk M., Schwab M. (2009). Validation of spontaneous assessment of baroreceptor reflex sensitivity and its relation to heart rate variability in the ovine fetus pre- and near-term. Can J Physiol Pharmaco l87(9):736-42.
Schwab M. (2009). Intrauterine Programmierung von Störungen der Hirnfunktion im späteren Leben. Gynäkol Geburtshilfliche Rundsch 49(1):13-28.
Schwab K., Groh T., Schwab M., Witte H. (2009). Nonlinear analysis and modeling of cortical activation and deactivation patterns in the immature fetal electrocorticogram. Chaos 19(1):015111.
Rupprecht S., Hagemann G., Witte O.W., Schwab M. (2009). Alveolar hypoventilation as the first symptom of muscle weakness in facioscapulohumeral muscular dystrophy. Sleep Medicine 10(5):592-3.
Frasch M.G., Müller T., Hoyer D., Weiss C., W. Schubert H., Schwab M. (2009). Nonlinear properties of vagal and sympathetic modulations of heart rate variability in ovine fetus near term. Am J Physiol 296(3):R702-7.
Frasch M.G., Müller T., Wicher C., Weiss C., W. Schwab K., Schubert H., Schwab M. (2009). Heart rate variability analysis allows early asphyxia detection in ovine fetus. Reprod Sci 16(56):509-17.
Antonow-Schlorke I., Helgert A., Gey C., Coksaygen T., Schubert H., Nathanielsz P.W., Witte O.W., Schwab M. (2009). Adverse effects of antenatal glucocorticoids on cerebral myelination in sheep are dose dependent and specific to the fetal stage of development. Obstet Gynecol 113(1):142-151.
RupprechtS., Hutschenreuther J., Brehm B., Witte O.W., Schwab M. (2008). The causality in the relation of Cheyne-Stokes respiration and paroxysmal atrial fibrillation. Sleep Medicine 9:462-464.
Raschke C., Schmidt S., Schwab M., Jirikowski G. (2008). Effects of betamethasone treatment on central myelination in fetal sheep: an electron microscopical study. Anat Histol Embryol 37:95-100.
McCallum J., Smith N., Schwab M., Nathanielsz P.W., Coksaygan T., Reinhardt B., Richardson B. (2008). Effects of antenatal glucocorticoids on cerebral substrate metabolism in the pre-term ovine fetus. Am J Obstet Gynecol 198:105.e1-9.
McCallum J., Smith N., MacLachlan J.N., Coksaygan T., Schwab M., Nathanielsz P.W., Richardson B. (2008). Effects of antenatal glucocorticoids on cerebral protein synthesis in the pre-term ovine fetus. Am J Obstet Gynecol 198:103.e1-6.
Antonow-Schlorke I., Müller T., Brodhun M., Wicher C., Schubert H., Nathanielsz P.W., Witte O.W., Schwab M. (2007) Betamethasone related acute alterations of microtubule associated proteins in the fetal sheep brain are reversible and independent of age during the last third of gestation. Am J Obstet Gynecol 196:553.e1-6. (“Editors choice”)
Frasch M.G., Müller T., Wicher C., Weiss C., W. Löhle M., Schwab K., Schubert H., Nathanielsz, P.W., Witte O.W., Schwab M. (2007). Fetal body weight and the development of the control of the cardiovascular system in fetal sheep. J Physiol (Lond) 579:893-907.
Schwab M. (2007). Fetal brain development and the programming of cerebral disorders. Der Gynäkologe 40:256-263.
Schwab M., Fitzek C., Witte O.W., Isenmann S. (2007). Extending the potential of perfusion imaging with MRI to prevent major stroke. Lancet Neurol 6:102-104.
Antonow-Schlorke I., Ebert M., Cun L., Gschanes A., Witte O.W., Nathanielsz P.W., Schwab M. (2007) Effects of antenatal glucocorticoid therapy on glucose transporter proteins in the fetal baboon brain. J Med Primatol 36:17-20.
Frank B, Frasch MG, Schneider U, Roedel M, Schwab M, Hoyer D. (2006) Complexity of heart rate fluctuations in near-term sheep and human fetuses during sleep. Biomed Tech (Berl). 51:233-6.
Schwab M., Coksaygan T., Samtani M., Jusko W.J., Nathanielsz P.W. (2006) Kinetics of betamethasone and fetal cardiovascular adverse effects in pregnant sheep after different doses. Obstet Gynecol 108:617-25.
Antonow-Schlorke I., Ebert M., Müller T., Coksaygan T., Schubert H., Gschanes A., Witte O.W., Nathanielsz P.W., Schwab M. (2006) Glucocorticoid effects on glucose transporter proteins in the fetal sheep brain. Neurosci Lett 403(3):261-265.
Schwab M., Coksaygan T., Nathanielsz P.W. (2006).Betamethasone effects on ovine uterine and umbilical placental perfusion at the dose used to enhance fetal lung maturation. Am J Obstet Gynecol 194:572-579.
Schwab M. (2005). Pränataler Stress, sensorische Stimuli und die Programmierung des ZNS. Thüringer Ärzteblatt 10: 468-470.
Löhle M., Müller T., Wicher C., Roedel M., Schubert H., Nathanielsz P.W., Witte O.W., Schwab M. (2005). Betamethasone effects on fetal sheep cerebral blood flow are not dependent on maturation of cerebrovascular system and pituitary-adrenal axis. J Physiol (Lond) 564:575-588.
Samtani M.N., Schwab M., Nathanielsz P.W., Jusko W.J. (2004). Area/moment and compartmental modeling of pharmacokinetics during pregnancy: applications to maternal/fetal exposures to corticosteroids in sheep and rats. Pharm Res 21:2279-2292.
ColbergC., Antonow-Schlorke I., Müller T., Schubert H., Nathanielsz P.W., WitteO.W., Schwab M. (2004). Recovery of glucocorticoid-related loss of synaptic density in the fetal sheep brain at 0.75 of gestation. Neurosci Lett 364:130-134.
Samtani M.N., Schwab M., Nathanielsz P.W., Jusko W.J. (2004). Stabilization and HPLC analysis of betamethasone sodium phosphate in plasma. J Pharm Sci 93: 726-732.
Antonow-Schlorke I., Schwab M., Li C., Nathanielsz P.W. (2003). Glucocorticoid exposure at the dose used clinically alters cytoskeletal proteins and presynaptic terminals in the fetal baboon brain. J Physiol (Lond) 547: 117-123. (Artikel erhielt Titelblatt des Journals).
Müller T., Schubert H., Schwab M. (2003). Early prediction of fetal numbers in sheep based on peripheral plasma progesterone concentrations and season of the year. Vet Rec 152:137-8.
Müller T., Löhle M., Schubert H., Wicher C., Antonow-Schlorke I., Sliwka U., Nathanielsz P.W., Schwab M. (2002). Developmental changes in cerebral autoregulatory capacity in the fetal sheep parietal cortex. J Physiol (Lond) 539: 957-67.
Schwab M., Rödel M., Schmidt K., Müller T., Schubert H., Anwar M. A., Nathanielsz P.W. (2001). Nonlinear changes of electrocortical activity after antenatal betamethasone treatment in fetal sheep. J Physiol (Lond) 531: 535-543.
Schwab M., Antonow-Schlorke I., Kühn B., Müller T., Schubert H., Walter B., Sliwka U., Nathanielsz P.W. (2001). Effect of antenatal betamethasone treatment on microtubule associated proteins MAP1B and MAP2 in fetal sheep. J Physiol (Lond) 530: 497-506. (Artikel erhielt Titelblatt des Journals)
Antonow-Schlorke I., Kühn B., Müller T., Schubert H., Sliwka U., Nathanielsz P. W., Schwab M. (2001). Antenatal betamethasone treatment reduces synaptophysin in presynaptic terminals in the fetal sheep brain. Neurosci Lett 297: 147-150.
Schwab M., Rödel M., Anwar M. A., Buchwalder L.F., Müller T., Schubert H., Walter B., Nathanielsz P.W. (2000). Effects of betamethasone administration to the fetal sheep in late gestation on fetal cerebral blood flow.J Physiol (Lond) 528: 619-632.
Schmidt K., Kott M., Müller T., Schubert H., Schwab M. (2000). Developmental changes in the complexity of the electrocortical activity in fetal sheep. J Physiol (Paris) 94: 435-443.
Schwab M., Schmidt K., Witte H., Abrams R.M. (2000). Investigation of nonlinear ECoG changes during spontaneous sleep state changes and cortical arousal in fetal sheep. Cereb Cortex 10: 142-148.
Schmidt K., Schwab M., Abrams R.M., Witte H. (1999). Nonlinear analysis of the fetal ECoG: predictability and bispectral measures. Theor Biosci 118: 219-230.
Witte H., Breidbach O., Schmidt K., Schwab M. (1999). News and views in signal analysis of the electröncephalogram (EEG). Theor Biosci 118: 284-299.
Anwar M. A., Schwab M., Poston L., Nathanielsz P. W. (1999). Betamethasone mediated vascular dysfunction and changes in hematological profile in the ovine fetus. Am J Physiol 276: H1137-1143.
Schwab M., Antonow-Schlorke I., Zwiener U., Bauer R. (1998). Brain derived peptides reduce the size of cerebral infarction and loss of MAP2 after focal ischemia in rats. J Neural Transmiss Suppl. 53: 299-311.
Antonelli P., Abrams R.M., Gerhardt K.J., Schwab M., Bauer R. (1998). Vestibular function of the fetal sheep. Otolaryngol Head Neck Surg 118: 571-575.
Abrams R.M., Schwab M., Gerhardt K.J., Bauer R., Antonelli P. (1998). Caloric stimulation of the inner ear in fetal sheep: Effect on eye movements and electrocorticogram. Int J Ped Otorhinolaryngol 45: 59-68.
Schwab M., Bauer R., Zwiener U. (1998). Mild hypothermia prevents the occurrence of cytotoxic brain edema in rats. Acta Neurobiol Exp 58: 29-35.
Schwab M., Bauer R., Zwiener U. (1997). The distribution of normal brain water content in wistar rats and its increase due to ischemia. Brain Res 749: 82-87.
Schwab M., Schaller R., Bauer R., Zwiener U. (1997). Morphofunctional effects of permanent bilateral carotid occlusion and short-term hypoxia in rats. Exp Tox Pathol 49: 29-37.
Schwab M., Bauer R., Zwiener U. (1997). Physiological effects and brain protection by hypothermia and Cerebrolysin after permanent bilateral carotid artery clamping in rats. Exp Tox Pathol 49: 105-116.
Bauer R., Schwab M., Abrams R.M., Stein J., Gerhardt K.J. (1997). Electrocortical and heart rate response during vibroacoustic stimulation in fetal sheep. Am J Obstet Gynecol 177: 66-71.
Schwab M., Antonow-Schlorke I., Dürer U., Bauer R. (1996). Effects of Cerebrolysin on cytoskeletal proteins after focal ischemia in rats. J Neural Transmission Suppl 47: 279.
Abrams R.M., Schwab M., Gerhardt K.J., Bauer R., Peters A.J.M. (1996): Vibroacoustic stimulation with a complex signal: Effect on behavioral state in fetal sheep. Biol Neonate 70: 155-164.
Contributions to books and proceedings
RupprechtS., Hoyer D., Schwab M. (2009). REM-Schlaf-assoziierte Bradyarrhythmie. In: Kompendium Schlafmedizin eds. Schulz, Geisler, Rodenbeck. Ecomed, 13. Erg.Lfg., XVII-5.3.8.
Schwab M., Einhäupl K.M., Witte O.W. (2006). Infektionen des ZNS. In: Intensivmedizin eds. Van Aken, Reinhart, Zimpfer, Welte. Thieme, 2. Auflage, 716-739.
Schwab M. (2004). Geräusche und Stresshormone im Mutterleib - Was nimmt der Fetus wahr und was prägt ihn für den Rest des Lebens? Nova Acta Leopoldina 18 (Suppl.): 219-250.
Schmidt K., Schwab M., Kott M., Szeto H.H. (1998). Nonlinear Investigation of developmental changes of the ECoG activity in fetal sheep. Proc Int Conf IEEE Engin Med Biol Soc 20: 2034-2037.
Schmidt K., Schwab M., Witte H. (1998). Different states of cortical function in the fetal brain - analysis of nonlinear predictability and bispectral measures. Med Inform Biometr Epidemiolog 85: 202-203.
Schwab M., Schmidt K., Bauer R., Abrams R.M. (1997). Linear and nonlinear changes of the ECoG during vibroacoustic stimulation of the fetal sheep. In: Schack B., Witte H., Zwiener U. (eds.) Quantitative and topological EEG and MEG Analysis II, Universitätsverlag Druckhaus Mayer GmbH, Jena: 190-193.
Schmidt K., Eiselt M. Schwab M., Bauer R., Zwiener U., Hoyer D. (1997). The quality of the point prediction error to quantify and classify state changes. In: Schack B., Witte H., Zwiener U. (eds.) Quantitative and topological EEG and MEG Analysis II, Universitätsverlag Druckhaus Mayer GmbH, Jena: 263-266.
Schwab M., Bauer R., Zwiener U. (1995). Different effects of forebrain ischemia on ECoG in relation to body temperature. In: Eiselt M., Zwiener U. Witte H. (eds.) Quantitative and topological EEG and MEG Analysis, Universitätsverlag Druckhaus Mayer GmbH, Jena: 237-242.
Schwab M., Bauer R., Zwiener U. (1995). Effects of CERE on ECoG during moderate forebrain ischemia under normothermic and hypothermic conditions. In: Eiselt M., Zwiener U., Witte H. (eds.) Quantitative and topological EEG and MEG Analysis, Universitätsverlag Druckhaus Mayer GmbH, Jena: 243-248.
Schaller R., Schwab M., Bauer R., Zwiener U. (1992). EEG analysis and comparison to morphological changes after hypoxic ischemic brain injury in rats. In: Quantitative EEG analysis - clinical utility and new methods. PMI-Verlagsgruppe Universitätsverlag GmbH Jena: 127-132.
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