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A Closer Look at the Blood-Brain Barrier

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In order to cure illnesses relating to the brain, various kind of simulators are placed deep inside the human brain. Sometimes, things like tubes, catheters, etc., are penetrated deep into the brain ventricles for delivering analgesic, chemotherapy, or to drain out excess cerebral liquids. Take the example of the Ommaya reservoir which is frequently used “ it is simply thrust into the brain without caring about the brain tissues that come in its path. The need of the moment is that we should design delicate instruments for the brain, which works with the brain's natural barriers rather than against it. For that we must have the knowledge of membranes of the brain that balances the fluid's constitution, the way it seals the brain blood vessels, etc.

It is interesting to note that pathogens like the viruses, bacteria, fungi, etc., have their own tricks to invade the brain by bypassing its natural barriers. They find a way to enter if the infection persists long enough. Researchers are now wondering if they could apply the same Brain Blood Barrier (BBB) busting skills of the microbes to artificial devices for the brain. Typically, we do not insert a recording or stimulating electrode in the brain through the vasculature, however it could in fact be the most least invasive methods that could help us in enabling future technologies like the smart-dust, optogenetics, etc.

In order to be able to see the mysterious BBB, researchers used superparamagnetic iron oxide nanoparticles (SPION) encapsulated with inert hydrophilic polyethylene glycol (PEG) and obtained the MRI images of the BBB. MRI images of the BBB when it dynamically responds to assault were also recorded. These carefully-engineered nanoparticles are called PEGylated SPIONs by the researchers. These SPIONs did a great job at enhancing T2-weighted images of the permeabilized BBB.

The researchers also were able to analyze the SPION level in the brain parenchyma itself. For the brain, “Parenchyma generally means the neurons and glial cells. It is estimated that there are over 100,000 miles of astrocytic endfeet-lined capillary tubing in its fractal coastline. In fact, the BBB and other membranous ventricular linings might be considered an organ itself.

The T2-weighted scans can give greater detail in imaging various brain pathologies.  It will be useful to know about the history of BBB to under the work better. A century ago, BBB was discovered by scientists when they were trying to find a way to insert drugs in to a brain for treatment of African trypanosomiasis (sleeping sickness). Scientist Paul Ehrlich was the first person who successfully developed a treatment against the African trypanosomes that caused the disease. He was the man who coined the terms “chemotherapy” and “magic bullet” after the trypan dyes which could kill the parasite’s cells while sparing the healthy cells.

It was then noted that when the trypan dyes are injected into the bloodstream, it would not label the brain. That meant that there was some kind of border. One thing that emerged from that research of trypanosomes is endocytosis – a core principle in cell biology and neuroscience. One of the key events in infection is that the pathogens gain passage through membrane boundaries by budding in through in vesicles. The BBB is lined by the endothelial cells – similar to those found in any other organs yet are held to a slightly higher standard. The junctions they make are tighter, and subject to more points of control.

Doctors today have a few crude tricks they can use to manipulate the BBB. However, those techniques are not very high tech. It is important to have a way for non-invasive measurements of flow and pressure as it will be essential to understand what is happening inside the brain when it has been altered by natural or by artificial means.