The Blood-Brain Barrier in Brain Tumours

Abstract

The literature on glioblastoma is increasingly concerned with genetic pathways to and genomic analyses of glioblastoma (Ohgaki et al., 2004; Parsons et al., 2008). Mutations of numerous genes were demonstrated to be involved in the development of brain tumours; however, in most cases the mechanistic roles of these mutated genes in the dysregulation of the cells of tumour origin are not understood in functional terms, but are used for molecular diagnostics (Riemenschneider et al., 2010). Moreover, several potential biomarkers of glioblastoma were identified and classified for clinical prognosis without precise knowledge of their function (Sreekanthreddy et al., 2010). A new dimension of brain tumour research has been reached by the detection of cancer stem cells in glioblastoma which were identified as a small subpopulation of brain tumour propagating cells (Huang et al., 2010; Tabatabai & Weller, 2011). A link between glioblastoma stem cells and tumour vascularization has been established by the first description of the possibility that tumour vessels can be recruited from glioblastoma stem cells (Ricci-Vitiani et al., 2010). This opens a new field concerning the plasticity of tumour vessel endothelial cells including their lost or undifferentiated barrier properties. Since the clinical signs of the glioblastoma are connected to the intracerebral pressure due to edemas, understanding the alterations of the blood-brain barrier (BBB) is of central importance. For this reason, we will begin this chapter on the blood-tumour barrier with the description of cell biological aspects of the healthy BBB. The BBB is responsible for the homeostasis of the microenvironment in the neural parenchyma and essential for normal function of the brain. In the strict sense, it is located in the endothelial cells and restricts the paracellular diffusion of hydrophilic molecules by both complex tight junctions (Reese & Karnovsky, 1967; Brightman & Reese, 1969) and a low degree of transcytosis (Peters et al., 1991). This implies the necessity of various specific transporters for providing the brain with compounds essential for brain energy metabolism (Begley, 2004). It is generally accepted now that astrocytes play a decisive role in the maintenance if not induction of the BBB (Abbott et al., 2006; Wolburg et al., 2009). But we have to be aware that the mechanism by which this maintenance or induction of the BBB is performed, is not understood so far. In any case, in the mature brain, the astrocytes embrace the vessels by sending an endfoot towards the perivascular basal lamina (Mathiisen et al., 2010). It has