Assessment of Blood–Brain Barrier Breakdown - Animal Models of Acute Neurological Injuries: Injury and Mechanistic Assessments - page 381

Chapter 28
Assessment of Blood-Brain Barrier Breakdown
Yoash Chassidim , Ofer Prager , Ilan Shelef , and Alon Friedman
Abstract
The blood-brain barrier (BBB) is a structural and functional barrier which limits the free passage of ions
and large molecules between the blood and brain. BBB functions are often impaired in neurological disor-
ders, more often in vascular-related injuries, stroke, intracerebral, and subarachnoid hemorrhage. Recently,
it has been demonstrated that injury to the BBB and the diffusion of serum proteins into the brain's
extravascular space are directly related to immediate astrocytic transformation followed by neuronal dys-
function and delayed structural damage. Despite the increasing awareness to the potential importance of
the BBB as a diagnostic and therapeutic target, there is still clear lack of quantitative and sensitive methods
to measure BBB permeability. Here, we present a novel dynamic approach to detect and quantify BBB
breakdown in the rat cerebral cortex using in vivo imaging. We further present alternative common
methodologies.
Key words: Blood-brain barrier, Dynamic imaging, In vivo
1. Introduction
Proper neuronal functions within the central nervous system (CNS)
necessitate a highly regulated extracellular environment, wherein
the concentrations of ions (e.g., Na + , K + , Cl − , and Ca 2+ ), amino
acids, and metabolites are kept within very narrow ranges. In addi-
tion, different chemicals and metabolites consumed in our diet, or
metabolized and excreted in peripheral organs, may affect neuronal
functions or damage the delicate and highly regulated functional
network of the CNS. It is therefore essential that the interface
between the CNS and the peripheral circulatory system functions
as a dynamic regulator of ion balance, a facilitator of nutrient trans-
port, and a barrier against potentially harmful molecules (for review,
see ref. ( 1 )). From the three barrier layers (i.e., blood-brain barrier
(BBB), choroid plexus epithelium and arachnoid epithelium) that