The use of lasers to temporarily open up the blood-brain barrier (BBB) may improve brain tumor treatments by providing drugs with access to the cancerous cells, according to a new study published in the journal PLOS ONE.
At present, fewer than 5 percent of patients diagnosed with glioblastoma (GBM) – the most common type of brain cancer – survive for more than five years after diagnosis. One of the major obstacles to combating this type of tumor is the fact that chemotherapy drugs are unable to cross the BBB.
This semi-permeable membrane separates the blood from the cerebrospinal fluid, and regulates the diffusion of material into and out of the brain. While it plays an important role in protecting cerebral tissue, scientists looking for ways to treat brain tumors have focused a great deal of attention on finding a method of bypassing this barrier in order to deliver drugs to the relevant area.
Though no long-term effective treatment for GBM currently exists, many patients undergo a procedure called laser interstitial thermal therapy (LITT). This involves making a small incision in the skull, through which a laser is fired in order to kill the cancer cells by heating them up to around 65°C (149°F). This technique has been found to increase the amount of time that people with GBM are able to survive, although the researchers behind the latest study have found that it may have another, unexpected effect, which could allow for the development of more effective treatments.
The blood-brain barrier regulates the movement of material between the bloodstream and the cerebrospinal fluid. Armin Kübelbeck via Wikimedia Commons
After performing LITT on 14 GBM patients, the study authors sought to trace the effect that the this had on the BBB. To do so, they employed a special MRI technique at several intervals in the weeks following the procedure. These scans enabled them to track the movement of content across the BBB, and revealed that the volume of this increased significantly following LITT, before steadily falling back to regular levels around four weeks later.
At the same time, they measured concentrations of an enzyme called brain-specific enolase (BSE) in the blood. Since this compound exists only in the brain itself, any movement of BSE into the bloodstream essentially indicates a leak in the BBB.
Results showed that BSE concentrations did indeed rise in the blood following LITT, peaking around one to two weeks after the procedure, before returning to normal after about four to six weeks.
This led the researchers to conclude that LITT causes a temporary opening in the BBB, which reaches its maximum permeability after a week or two, before closing up again at the four to six week mark. As such, they suggest that LITT may provide a window of opportunity for the delivery of chemotherapy drugs into the brain, and urge scientists to re-open trials of failed cancer medications by combining them with LITT.
In addition, the study authors suggest that a temporary opening in the BBB could also provide a chance for certain components of the body’s own immune system – which can’t normally cross this barrier – to do so and initiate an immune response against the brain tumor.