**Blood-Brain Barrier in Glioma Therapy**

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**7** 

*Iran* 

**Blood-Brain Barrier and Effectiveness of** 

The challenge to comprehend the physiology as well as cell biology of the blood-brain barrier (BBB) began with Ehrlich and Goldman's experimental observations that the central nervous system (CNS) is not stained by intravascular vital dyes. These studies provided the first evidence of the presence of an obstructing barrier between blood and brain. Later on, researchers like Friedemann (1942) used basic highly lipid soluble dyes to cross the BBB in order to show the brain penetration of the dyes by direct transport across the cerebral microvasculature. In 1941, Broman presented his observations upon the existence of two different barrier systems within the brain: the BBB at the cerebral microvasculature, and the blood-CSF barrier at the choroid plexus. It is now clear that in fact three main barrier layers at the interface between blood and tissue protect the CNS: the endothelium of brain capillaries, and the epithelia of the choroid plexus (CP) and the arachnoid (Abbott, 2005;

In 1941, Broman proposed that it was the cerebral capillary endothelial cells that contribute the physical barrier function of the BBB, and not the astrocytic end feet. The argument concerning whether the astrocytes or the capillary endothelium constitute the BBB was supported by electron microscopic cytochemical studies performed in 1967 by Reese and Karnovsky. They used horseradish peroxidase (HRP), ~40 kDa, to visualize the BBB by systemic injections of HRP which failed to reach the brain extracellular fluid, whereas intracerebroventricular injection into the CSF stained the brain extracellular fluid positive

It is now evident that the BBB is a unique membranous barrier, which restrictively isolates the brain parenchyma from the circulating molecules/compounds within the blood. The permeability of BBB is regulated by transport machineries of the brain capillary endothelial cells that are modulated by autocrine and paracrine secretions from several types of cells,

The pericyte cells share the capillary basement membrane with the endothelium and physically supports endothelial cells (Allt & Lawrenson, 2001). It has been revealed that there is approximately one pericyte for every three endothelial cells (Pardridge, 1999). It is deemed that the pericyte cells play a regulatory role in brain angiogenesis, endothelial cell

such as the pericyte, the astrocyte, and neurons (Rubin & Staddon, 1999).

**1. Introduction** 

Engelhardt, 2006).

for HRP (Reese & Karnovsky, 1967).

*Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz,* 

**Therapy Against Brain Tumors** 

*Research Center for Pharmaceutical Nanotechnology,* 

Yadollah Omidi and Jaleh Barar
