Biomedical Engineering Reference
In-Depth Information
7.4.5
BBB Formation
During embryogenesis, the blood-brain barrier forms when endothelial cells invade
the central nervous system from the surrounding vascular plexus and PDGFR
, 33
β+
34 pericytes are recruited to the nascent vessels, before astrocyte gener-
ation [ 678 ]. 35 Pericyte-endothelial cell interactions control the developing blood-
brain barrier. However, even in the absence of pericytes, embryonic CNS endothelial
cells express many BBB-specific molecules via interactions with neural progenitors.
Neural progenitors secrete Wnt morphogens for angiogenesis as well as production
of BBB-specific transporters.
Pericyte coverage determines vascular permeability. Pericytes regulate the for-
mation of tight junctions and vesicle transfer in CNS endothelial cells [ 678 ].
Pericytes prevent the synthesis of molecules that increase vascular permeability
and leukocyte infiltration. 36 Pericytes may thus provide signals to limit immune
surveillance in the central nervous system. Afterward, astrocytes likely regulate the
maintenance of the blood-brain barrier as well as repair after injury. The functional
integrity of the blood-brain barrier is thus controlled by pericytes during embryo-
and fetogenesis and by astrocytes in adulthood [ 678 ].
CSPG4
+
7.5
Other Cerebral Epithelial Barriers - Choroid Plexi
In addition to the blood-brain barrier endothelium, 2 other cell layers with tight
junctions provide a barrier: (1) arachnoid epithelium that forms the middle layer of
the meninges and (2) choroid plexus epithelium.
Choroid plexi form an active barrier between blood and cerebrospinal fluid
(CSF). 37 They secrete the cerebrospinal fluid and ensure its chemical stability. They
localize to the surface of the lateral, third, and fourth ventricles. They are made
of 2 cell layers that are bound by tight junctions: a capillary endothelium and a
33 PDGFR: platelet-derived growth factor receptor.
34 CSPG: chondroitin sulfate proteoglycan-4, or neuron-glial antigen NG2.
35 Neural cells are produced from progenitors in a defined sequence, with neurons generated
before glial cells. Oligodendroglia progenitor cells and PDGFR
α+
,CSPg4
+
glial cells migrate
throughout the cortex.
36 In the absence of PDGFR
β
in the vasculature, the transcription of several leukocyte adhesion
molecules, such as intercellular adhesion molecule ICAM1, activated leukocyte cell adhesion
molecule (ALCAM), and lectin, galactoside-binding, soluble LGalS3, is upregulated [ 678 ].
37 Cerebrospinal fluid is located within the head ventricles, spinal canal, and subarachnoid spaces.
Its volume ranges from 140 to 150 ml, with 30 to 40 ml in the ventricles. Hence, CSF is mainly in
the subarachnoid space, basal cisternae, and around the spinal cord. The production rate is equal to
about 21 ml/h and the turnover rate of total CSF is smaller than 7 h. Cerebrospinal fluid cushions
the brain, regulates brain extracellular fluid, distributes neuroactive substances, and collects brain
wastes.
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