As we know, the blood brain barrier
has extremely selective permeability to protect the microenvironment of
neurons. Understandably, fluctuations in systemic blood components need to be
tightly controlled to maintain the integrity of the cerebral circulation. For
example, eating a protein rich meal will increase the concentration of certain
amino acids that serve as neurotransmitters, causing inappropriate neuronal
stimulation if there was no barrier in place (Boron & Boulpaep 2012).
The anatomy of the brain helps to
select for solutes that can pass from the blood to the brain extracellular
fluid (BECF). Capillary endothelial cells are found in the brain capillaries
and, unlike other body capillaries, they are connected to each other by
continuous tight junctions, providing the physical barrier to certain solutes (Boron
& Boulpaep 2012). To reiterate, certain solutes such as O2 or caffeine
can pass the blood brain barrier due to their properties, but other molecules,
such as potassium ions have a more limited access.
Capillaries of the brain. Photo credit: Dan Ferber.
Conceivably, this makes clinical
treatments that would otherwise target certain brain conditions, difficult. For
example, in the treatment of brain tumors, the successful passage of certain small
chemotherapeutic drugs is necessary (Silva 2008). Some therapies attempt to
pair therapeutic drug agents to transporters with the ability to cross the
barrier, however, this is not always efficient and has the potential to cause
other side effects—this emphasizes a need to explore the ability to manipulate
the blood brain barrier (Silva 2008).
A recent study sought to research
this particular concept, but with a completely novel approach. This new methodology
involves placing ultrasound emitters in the brains of patients with
glioblastoma (brain tumors). The pulses created by the ultrasound cause
vibrations that separate the capillary endothelial cells in a specific region,
for a specific period of time, allowing access to the brain extracellular fluid
(Canney et al. 2013). This access allows for the delivery of drugs that can
ablate the tumor and, in this study, allowed the barrier to remain open for up
to six hours. The long term effects/success of this treatment are still being
established, as the status of the tumors is still being measured; however,
limited peripheral tissue damage was observed. This has huge implications, not
only for administering chemotherapy, but also has been shown to reduce protein
plaque in the brains of mice with a disease comparable to human Alzheimer’s
(Thomson 2014).
As we know, scientific breakthroughs
come in small steps and more research is necessary to better understand the
success and capacity of this new ultrasound approach. What do you think about
its potential? What about possible consequences to opening the blood-brain
barrier for six hours?
References:
Boron WF, Boulpaep EL. 2012. Medical Physiology. 2nd ed. Philadelphia: Saunders. 298-301 p.
Canney MS, Chavrier F, Tsysar S, Chapelon J, Lafon C,
Carpentier A. 2013. A multi-element interstitial ultrasound applicator for the
thermal therapy of brain tumors. The Journal of the Acoustical Society of
America. 134:1647-1655.
Ferber D. Bridging the Blood-Brain Barrier: New Methods Improve
the Odds of Getting Drugs to the Brain Cells That Need Them. PLoS Biology 5(6):169.
Silva GA. 2008. Nanotechnology approaches to crossing the
blood-brain barrier and drug delivery to the CNS. BioMed Central Neuroscience.
9(3): S4.
Thomson H. 2014 Oct. 22. Brain barrier opened for first time
to treat cancer. New Scientist [Internet]; 2922. Available from: http://www.newscientist.com/article/dn26432-brain-barrier-opened-for-first-time-to-treat-cancer.html#.VH0uNzHF-Sq
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