The Blood Brain Barrier and Treatment of Brain Tumors

 

A recent report in New Scientist describes what is being called a breakthrough in terms of scientists ability to open the blood brain barrier. http://www.newscientist.com/article/dn26432-brain-barrier-opened-for-first-time-to-treat-cancer.html#.VFppMiiZPZR

What is the blood brain barrier and why is this important for glioblastoma patients, and is this truly a breakthrough?  First, it should be noted that most blood vessels in the body that supply tissues are comprised of small capillaries that allow most drugs to seep through from the blood, through the capillary wall and into the adjoining tissue. The brain has a much more impermeable series of capillaries, and because of this, many molecules are unable to enter the brain tissue. This may serve as a way to protect the brain from certain toxic molecules. However, in terms of drug delivery for brain diseases, this poses a barrier because many drugs are unable to cross the blood-brain barrier, and for this reason they do not actually get into the tissues that are trying to be treated.

It should be noted however that the blood vessels in patients that have high grade gliomas and glioblastoma are often abnormal and do not really have a blood-brain barrier. Therefore, there is a common misconception that the blood-brain barrier must be overcome in order for molecules to get to the brain tumor cells. This is only partially true. We know that gadolinium, which is a large molecule used as a contrast agent on MRI scans, does go into glioblastoma tumors, but not into normal brain. This is an example of how certain molecules are able to cross into tumor cells from the blood whereas they do not get into the normal brain.

Nevertheless, other molecules still have difficulty getting into brain tumor cells. The group that reported this most recent finding has used a very novel technique that facilitates opening up capillary cells and making them more permeable in the normal brain scenario. Microbubbles are administered intravenously to patients and a small ultrasound device in the brain makes these microbubbles vibrate. These vibrations open up the capillaries so that other molecules can cross into the blood-brain barrier. This novel technology may have implications down the road for delivery of various drugs and compounds to the brain.

In the current scenario that was reported, a small ultrasound transducer catheter was placed directly into the brain tissue such that the surrounding brain area that was exposed to the ultrasound waves was able to cause the microbubbles to vibrate and open up the blood-brain barrier. It is hoped that by doing this, certain chemotherapy drugs that were previously inaccessible to brain tumors might be able to get into a glioblastoma or other tumor type more easily and deliver their payload there.

Another downstream application that can potentially utilize this technique is the Focused Ultrasound which we here at the Swedish Neurosciences Institute, and several other institutions in the world are pioneering for brain tumors. It is hoped that the use of Focused Ultrasound, which utilizes a noninvasive generation of thousands of ultrasound waves from outside of the skull to pinpoint an area of increased ultrasound focus, will be able to similarly cause microbubbles to increase their vibrations and open up the blood-brain barrier in a completely noninvasive way.

It should be noted that the study that was reported using a catheter causing the ultrasound waves and the noninvasive focused ultrasound technology is still years away from being able to apply these types of treatments to patients suffering from brain tumors currently. Nevertheless, these novel strategies are likely to have a significant impact in the future in terms of noninvasive or invasive techniques for increasing the blood brain barrier and increasing delivery of various chemotherapeutic agents or other compounds.

 

 

 

 

 

 

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