[gdpawel]

Avastin blocks VEGF and causes existing microcapillaries to die. This is what is measured with the AngioRx assay, death of existing endothelial cells of microcapillaries, and associated cells. Microcapillary blood vessels run throughout the brain in close proximity to brain cells.

Some clinical work on Avastin suggests that there could be several possible mechanisms for Avastin, including potentially decreasing the oncotic pressure within the center of a necrotic tumor, which can limit the ability of the drug it is given with to be delivered into the tumor.

The oncotic pressure (or colloid osmotic pressure) is a form of osmotic pressure exerted by proteins in blood plasma that usually tends to pull water into the circulatory system. Because "large" plasma proteins cannot easily cross through the capillary walls, their effect on the osmotic pressure of the capillary interiors will, to some extent, balance out the tendency for fluid to leak out of the capillaries (oncotic pressure tends to pull fluid into the capillaries).

A drop in vascular permeability induces trans-vascular gradients in oncotic and hydrostatic pressure iin blood vessels. The induced hydrostatic pressure gradient improves the penetration of large molecules (Avastin is a large molecule drug) into vessels.

Scientists from MD Anderson (and other institutions) have found out that they could treat radiation-induced necrosis of the brain with Avastin. Recent studies have shown that Avastin may be able to stop radiation necrosis of the brain and allow some of the damage to be reversed.

I can see where radiation can allow the lining of the brain to become permeable to VEGF, and VEGF can induce the brain cells to make more VEGF, and self-propagating brain damage ensues. And Avastin can disable VEGF.

The MD Anderson research team postulates that radiation therapy damages astrocytes, a cell type involved in various brain functions, and causes them to leak VEGF. This leaked VEGF might then cause further damage to brain cells and further leakage of VEGF. And the ultimate question is "is that all that's going on?"

With Hyperbaric Oxygen Therapy (HBOT), wound healing requires oxygen delivery to the injured tissues. Radiation damaged tissue has lost blood supply and is oxygen deprived. HBOT provides a better healing environment and leads to the growth of new blood vessels in a process called re-vascularization. HBOT acts as a drug when 100 percent oxygen is delivered at pressures greater than atmospheric (sea level) pressure to a patient in an enclosed chamber.

If this is the case, the judicious application of Avastin can normalize the vasculature by pruning the immature vessels and fortifying the remaining ones. Normalized vasculature is less tortuous and the vessels are more uniformally covered by pericytes (in capillaries which regulate the blood-brain barrier) and basement membrane (thin sheet of fibers which lines the interior surface of blood vessels).

Source: Cell Function Analysis