Biomedical Engineering Reference
In-Depth Information
3.
Blood-brain barrier
The brain is a unique organ highly protected by two major barriers, the BBB
which displays the largest surface area and the blood-cerebrospinal fluid
barrier (BCSFB). BBB is responsible for several functions, such as main-
tenance of neuronal microenvironment, tissue homeostasis, vasotonous
regulation, fibrinolysis and coagulation, blood cell activation and migration
during physiological and pathological processes. There are several gateways
which offer entry to brain parenchyma, the most important are blood circu-
lation and cerebrospinal fluid (CSF) circulation. In the human brain, there
are about 100 billion capillaries in total, providing a combined length of
brain capillary endothelium of approximately 650 km and a total surface
area of approximately 20 m
2
[12]. Despite the rapid development in under-
standing of the molecular structure of components of the BBB, knowledge of
receptor expression at the BBB, advances in medical technology, and break-
throughs in nanotechnology-based approaches, many of the CNS associ-
ated diseases remain under-treated by effective therapies. Since the majority
of drugs and large molecular weight particulate agents such as recombinant
proteins, peptides, monoclonal antibodies, small-interfering RNA (siRNA)
and gene therapeutics do not readily permeate into the brain parenchyma,
one of the most significant challenges facing CNS drug development, is the
availability of effective brain drug targeting technology.
3.1 Blood-brain barrier physiology
Physiologically BBB is made up of three layers such as the inner endothelial
cell layer which forms the wall of the capillary and contains tight junctions,
followed by the presence of a basement membrane upon which pericytes
and astrocytic feet processes lie [13]. The BBB endothelial cells differ from
endothelial cells in the rest of the body by the absence of fenestrations, more
extensive tight junctions (TJs), and sparse pinocytic vesicular transport.
Endothelial cells TJs limit the paracellular flux of hydrophilic molecules
across the BBB. In addition to brain capillary endothelial cells, extracellular
base membrane, pericytes, astrocytes, and microglia are all integral parts of
the BBB supporting system. The capillary endothelial cell line the microves-
sels, which are coupled by much more TJ (zonulae occludentes) than found
in peripheral vessels. The endothelial cells secrete and are surrounded by
a basal lamina (BL), with the end-feet of astrocytic glial cells close on its
opposite side. Astrocytes are the most abundant non-neuron cells and play
many essential roles in the healthy CNS, including biochemical support of
endothelial cells which form the BBB, regulation of blood flow, provision
of nutrients to the nervous tissue, maintenance of extracellular ion bal-
ance, and in the repair and scarring process of the brain and spinal cord
following traumatic injuries. Pericytes are embedded in the BL between en-
dothelial cells and astrocyte cells, making particularly close contact with the
