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The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) are specific barriers between the blood circuit and the central nervous system (CNS). Whereas the BBB is formed by the endothelial cells of the brain capillaries with support by astrocytes and pericytes (neurovascular unit), the morphological correlate of the BCSFB are the epithelial cells of the choroid plexus. Both barriers can be used by infectious pathogens (viruses, bacteria and eukaryotic pathogens) to enter the CNS.
Subsequently, serious inflammatory reactions occur in the brain, e.g. meningitis or encephalitis. An important role during this process is played by immune cells of the host, which cross the BBB or BCSFB in response to the pathogens and contribute to inflammation. Another research focus is the entry of the BBB and/or the BCSFB by tumor cells, including neuroblastoma cells. Since most cytostatic drugs penetrate the BBB and the BCSFB rather poorly, the CNS presents a protected space for the tumor cells, which again can cause tumor progression during or following therapy.
The research of the Childrens Hospital targets the following goals:
- Establishment of functional in vitro models of the BBB and the BCSFB
- Analysis of interactions of pathogens and immune cells with host cells/receptors, especially with integrins and extracellular matrix
- Investigation of the host cell response following bacterial or viral stimulation and examination of signal transduction pathways and regulation of barrier function
- Analysis of the consequences of these interactions concerning transcription of inflammatory genes (e.g. cytokines), phagocytosis as well as antibacterial effector mechanisms
- Identification of rational goals for adjuvant therapy of invasive infections by deciphering pathogenic processes
- Detection of mechanisms of tumor cell transmigration across the BBB and the BCSFB in human in vitro models
- Determination of the influence of chemokines and cellular adhesion molecules on tumor cell transmigration
- Clarification of the functions of pro-inflammatory cytokines and chemotherapeutic drugs during transmigration of tumor cells
- Schwerk C, Tenenbaum T, Kim KS, Schroten H: The choroid plexus-a multi-role player during infectious diseases of the CNS. Front Cell Neurosci, 9: 80, 2015.
- Asmat TM, Tenenbaum T, Jonsson AB, Schwerk C, Schroten H: Impact of calcium signaling during infection of Neisseria meningitidis to human brain microvascular endothelial cells. PLoS One, 9: e114474, 2014.
- Schwerk C, Papandreou T, Schuhmann D, Nickol L, Borkowski J, Steinmann U, Quednau N, Stump C, Weiss C, Berger J, Wolburg H, Claus H, Vogel U, Ishikawa H, Tenenbaum T, Schroten H: Polar invasion and translocation of Neisseria meningitidis and Streptococcus suis in a novel human model of the blood-cerebrospinal fluid barrier. PLoS One, 7: e30069, 2012.
- Wewer C, Seibt A, Wolburg H, Greune L, Schmidt MA, Berger J, Galla HJ, Quitsch U, Schwerk C, Schroten H, Tenenbaum T: Transcellular migration of neutrophil granulocytes through the blood-cerebrospinal fluid barrier after infection with Streptococcus suis. J Neuroinflammation, 8: 51, 2011.
- Tenenbaum T, Papandreou T, Gellrich D, Friedrichs U, Seibt A, Adam R, Wewer C, Galla HJ, Schwerk C, Schroten H: Polar bacterial invasion and translocation of Streptococcus suis across the blood-cerebrospinal fluid barrier in vitro. Cell Microbiol, 11: 323-336, 2009.
- Tenenbaum T, Spellerberg B, Adam R, Vogel M, Kim KS, Schroten H: Streptococcus agalactiae invasion of human brain microvascular endothelial cells is promoted by the laminin-binding protein Lmb. Microbes Infect, 9: 714-720, 2007.
- Adam R, Rüssing D, Adams O, Ailyati A, Sik Kim K, Schroten H, Däubener W: Role of human brain microvascular endothelial cells during central nervous system infection. Significance of indoleamine 2,3-dioxygenase in antimicrobial defence and immunoregulation. Thromb Haemost, 94: 341-346, 2005.
- Tenenbaum T, Bloier C, Adam R, Reinscheid DJ, Schroten H: Adherence to and invasion of human brain microvascular endothelial cells are promoted by fibrinogen-binding protein FbsA of Streptococcus agalactiae. Infect Immun, 73: 4404-4409, 2005.
- Schroten H, Spors B, Hucke C, Stins M, Kim KS, Adam R, Däubener W: Potential role of human brain microvascular endothelial cells in the pathogenesis of brain abscess: inhibition of Staphylococcus aureus by activation of indoleamine 2,3-dioxygenase. Neuropediatrics, 32: 206-210, 2001.
- Däubener W, Spors B, Hucke C, Adam R, Stins M, Kim KS, Schroten H. Restriction of Toxoplasma gondii growth in human brain microvascular endothelial cells by activation of indoleamine 2,3-dioxygenase. Infect Immun, 69: 6527-6531, 2001.
Prof. Dr. Horst Schroten
Chair of the Children's Hospital
Medical Faculty Mannheim
Phone +49 621/383-2248