Brain Tumor Biology Laboratory

Basel, Switzerland

Brain Tumor Biology Laboratory

Basel, Switzerland
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Graumann U.,Swiss Paraplegic Research | Ritz M.-F.,Brain Tumor Biology Laboratory | Hausmann O.,Neuro and Spine Center
Current Neurovascular Research | Year: 2011

Disruption of the blood-spinal cord barrier (BSCB) and microvascular changes leading to reduction of blood supply represent hallmarks of spinal cord secondary injury causing further deterioration of the traumatized patient. Injury to the blood vessels starts with prominent hemorrhage and generation of inflammation. Furthermore, spinal cord ischemia and extravasation of blood components contribute to edema formation resulting in death of neural cells. Endogenous attempts of re-vascularization have been observed although these newly formed vessels display morphological and functional abnormalities. The unfavorable regulation of angiogenic and counterregulatory anti-angiogenic factors during the complicated course of vessel remodeling after SCI is suspected to participate in the failure of re-vascularization and vessel stabilization. Repression of the expression of angiogenic factors such as vascular endothelial growth factor-A (VEGF-A), placental growth factor (PlGF), angiopoietin-1 (Ang1), and platelet-derived growth factor-BB (PDGF-BB) contributes to vessel regression. Therefore, therapeutic applications of angiogenic factors following SCI are promising strategies to restore blood flow in the lesion. © 2011 Bentham Science Publishers.


Ritz M.-F.,Brain Tumor Biology Laboratory | Grond-Ginsbach C.,University of Heidelberg | Engelter S.,University of Basel | Lyrer P.,University of Basel
Current Neurovascular Research | Year: 2012

Cerebral small vessel disease (SVD) is an important cause of stroke, cognitive decline and vascular dementia (VaD). It is associated with diffuse white matter abnormalities and small deep cerebral ischemic infarcts. The molecular mechanisms involved in the development and progression of SVD are unclear. As hypertension is a major risk factor for developing SVD, Spontaneously Hypertensive Rats (SHR) are considered an appropriate experimental model for SVD. Prior work suggested an imbalance between the number of blood microvessels and astrocytes at the level of the neurovascular unit in 2-month-old SHR, leading to neuronal hypoxia in the brain of 9-month-old animals. To identify genes and pathways involved in the development of SVD, we compared the gene expression profile in the cortex of 2 and 9-month-old of SHR with age-matched normotensive Wistar Kyoto (WKY) rats using microarray-based technology. The results revealed significant differences in expression of genes involved in energy and lipid metabolisms, mitochondrial functions, oxidative stress and ischemic responses between both groups. These results strongly suggest that SHR suffer from chronic hypoxia, and therefore are unable to tolerate ischemia-like conditions, and are more vulnerable to high-energy needs than WKY. This molecular analysis gives new insights about pathways accounting for the development of SVD. © 2012 Bentham Science Publishers.


Sailer M.H.M.,Brain Tumor Biology Laboratory | Sailer M.H.M.,University of Basel | Gerber A.,Brain Tumor Biology Laboratory | Tostado C.,Brain Tumor Biology Laboratory | And 6 more authors.
Journal of Cell Science | Year: 2013

Neural stem cells (NSCs) typically show efficient self-renewal and selective differentiation. Their invasion potential, however, is not well studied. In this study, Sox2-positive NSCs from the E14.5 rat cortex were found to be non-invasive and showed only limited migration in vitro. By contrast, FGF2-expanded NSCs showed a strong migratory and invasive phenotype in response to the combination of FGF2 and BMP4. Invasive NSCs expressed Podoplanin (PDPN) and p75NGFR (Ngfr) at the plasma membrane after exposure to FGF2 and BMP4. FGF2 and BMP4 together upregulated the expression of Msx1, Snail1, Snail2, Ngfr, which are all found in neural crest (NC) cells during or after epithelial-mesenchymal transition (EMT), but not in forebrain stem cells. Invasive cells downregulated the expression of Olig2, Sox10, Egfr, Pdgfra, Gsh1/Gsx1 and Gsh2/Gsx2. Migrating and invasive NSCs had elevated expression of mRNA encoding Pax6, Tenascin C (TNC), PDPN, Hey1, SPARC, p75NGFR and Gli3. On the basis of the strongest upregulation in invasioninduced NSCs, we defined a group of five key invasion-related genes: Ngfr, Sparc, Snail1, Pdpn and Tnc. These genes were co-expressed and upregulated in seven samples of glioblastoma multiforme (GBM) compared with normal human brain controls. Induction of invasion and migration led to low expression of differentiation markers and repressed proliferation in NSCs. Our results indicate that normal forebrain stem cells have the inherent ability to adopt a glioma-like invasiveness. The results provide a novel in vitro system to study stem cell invasion and a novel glioma invasion model: tumoral abuse of the developmental dorsoventral identity regulation. © 2013. Published by The Company of Biologists Ltd.

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