Blood-brain barrier homeostasis

Once in the serum, aluminium can be transported bound to transferrin, and also to albumin and low-molecular ligands such as citrate. However, the transferrrin-aluminium complex will be able to enter cells via the transferrin-transferrin-receptor pathway (see Chapter 8). Within the acidic environment of the endosome, we assume that aluminium would be released from transferrin, but how it exits from this compartment remains unknown. Once in the cytosol of the cell, aluminium is unlikely to be readily incorporated into the iron storage protein ferritin, since this requires redox cycling between Fe2+ and Fe3+ (see Chapter 19). Studies of the subcellular distribution of aluminium in various cell lines and animal models have shown that the majority accumulates in the mitochondria, where it can interfere with calcium homeostasis. Once in the circulation, there seems little doubt that aluminium can cross the blood-brain barrier. 

Perhaps the main peroxide-induced alterations, within cells and tissues, are those that affect calcium and sodium homeostasis. Na, K-ATPase, which is considered as the core of the sodium pump , is strongly affected by peroxides, and especially by lipid hydroperoxides [137-139]. This implies that oxidative stress will usually be associated with cellular edema . Alternatively, activation of the Na, K-ATPase of vascular endothelia, such as the blood-brain barrier, will result in extracellular edema on the antiluminal side of the endothelium, due to massive influx of sodium ions [119]. 

In addition to the blood-brain barrier, two other barrier layers limit and regulate molecular exchange at the interface between the blood and the neural tissue and its fiuid spaces the choroid plexus epithelium between blood and ventricular CSF and the arachnoid epithelium between blood and subarachnoid CSF. These CNS barriers perform a number of functions such as the ionic homeostasis, the restriction of small molecule permeation, the specific transport of small molecules required to enter or leave the brain, the restriction and regulation of large molecule traffic by reducing the fluid-phase endocytosis via pinocytotic vesicles, the separation of peripheral and central neurotransmitter pools, and the immune privilege [16]. 

To maintain brain homeostasis, the blood-brain barrier selectively transports nutrients into the brain via the expression of a number of surface transporters. 

Janigro D. Blood-brain barrier, ion homeostasis and epilepsy possible implications towards the understand-... 

N. Weiss, et al.. The blood-brain barrier in brain homeostasis and neurological diseases, Biochim. Biophys Acta 1788 (4) (2009) 842-857. 

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