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BLOOD BRAIN BARRIER
LECTURE NOTES FOR SLIDES FROM MULTIPLE SOURCES NOT ORIGINAL WORK
The brain capillary is different from the general capillary. In the brain the capillary comprises the blood brain barrier. The blood brain barrier is a complex regulatory interface that is part structural, biochemical, enzymatic, pharmacological, electrical, and immunological. The brain capillaries are nonfenestrated, and they lack intracellular clefts and are closed circumferentially by tight junctions. The tight junctions have high electrical impedance and low permeability to polar substances. The brain capillary also has little to no pinocytotic vesicles. The lack of pinocytotic vesicles accounts for the near exclusion of plasma proteins from the CSF. The cerebral endothelial cells have three to five times the mitochondrial content of the systemic endothelial cells. This reflects the high energy demands of the endothelial cells in order to maintain the energy dependent transport mechanisms. Numerous astrocytic foot processes also surround the brain capillary.
(The capillaries in brain tumors are more of the systemic type than neuronal type and, therefore, have fenestrations, junctions and pinocytotic vessels that allow the movement of bulk water and the transport of proteins and albumin into the interstitium. This increase in edema in tumors is, therefore, dependent on the circulating serum plasma and not the tumor.)
Substances that cross the blood brain barrier are lipid soluble, low molecular weight, lack a protein bound state, and are nonpolarized or nonionized molecules. The blood brain barrier is normally permeable to glucose, low density lipoproteins, and transferrin. It is not permeable to ions, water or amino acids. The blood brain barrier is not present in the neural hypophysis, median eminence, subfornicele organ, pineal gland and the area postrema.
The blood brain barrier can be disrupted instantaneously at the time of trauma. Stretching a brain can stretch the tight junctions. Mechanical disruption also affects the subpial microvessels, releasing free radicals and inducing an increase in intracellular calcium. The calcium increase comes from extracellular and intracellular stores. The increase in intracellular calcium is not sustained if there is no hypoxia. Brain injury immediately opens the blood brain barrier, leading to vasogenic edema, which usually lasts approximately 30 minutes. The blood brain barrier opening can be prolonged by hypoxia. In contrast cytotoxic edema starts slowly between 30 minutes and one hour, and reaches its maximum in one to two weeks. Other than focal acute stretching of the cortex, it is not precisely known what is responsible for the immediate opening of the blood brain barrier and the resultant vasogenic edema. Some think that the systolic blood pressure surge after traumatic brain injury might account for the blood brain barrier opening, which under these conditions might last up to six hours. However, the (Continued on page 48)
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