Unraveling the Mysteries of the Blood-Brain Barrier

The biological phenomenon known as the blood-brain barrier was first observed by German scientist Paul Ehrlich in the late 1980s.  Since that time, the mechanisms by which the brain secures itself from the rest of the body have been a source of both wonder and bewilderment.

In recent years, this understanding has been transformed with the advent of new imaging technologies which have shown that the “barrier” is actually a dynamic “organ” with cells on each side actively communicating with each other and deciding which molecules to let through and which to block.   

Maiken Nedergaard, M.D., D.M.Sc. and her colleagues in the URMC Center for Translational Neuromedicine have been pioneers in deploying these new imaging systems to observe and understand how various systems in the brain perform critical but poorly understood functions such as the removal of waste.  Her lab’s work is highlighted in article out this month in Scientific American which discusses how our understanding of the form and function of the blood-brain barrier has evolved:

At the University of Rochester, the view through Maiken Nedergaard's “two photon” microscope is infinitely more dazzling than even Ehrlich could have imagined. Of course, unlike him, she is looking at a brain that is still inside a living, breathing animal (a mouse, to be precise). She has removed a bit of the creature's skull and injected dye into its circulation, and now she is watching the blood-brain barrier in real-time: individual cells are crossing out of the bloodstream across capillary walls, which consist of a single layer of endothelial cells. The march is stunning to behold, especially given how inaccessible the barrier was when Nedergaard started her career, some 20 years ago.

Before the advent of two-photon microscopy—an advanced form of imaging that can penetrate the top 300 microns of cortex—researchers could not do much better than Ehrlich; they studied dead tissue fixed to traditional microscope slides. Those kinds of experiments, Nedergaard says, told biologists very little about how the blood-brain barrier actually operates. That is because blood flow is essential to the proper functioning of both brain and barrier—just how essential has surprised and excited scientists who study the barrier.

For example, in a string of recent experiments Nedergaard and her colleagues have shown that when a given cluster of neurons is stimulated, the surrounding blood vessels increase in diameter, thus delivering more blood and nutrients to those neurons at the exact moment that the neurons start firing. If you slow down that stimulation, the vessels contract, and nutrient delivery diminishes.

You can read the full Scientific American article here (subscription required).