Overcome the barrier
Ultrasound will help in the fight against brain cancer and Alzheimer's disease
Kirill Stasevich, "Science and Life"
When treating the brain, one inevitably has to face the problem of the blood-brain barrier (BBB), through which drugs simply cannot pass. The walls of cerebral blood vessels serve as an insurmountable barrier to all kinds of pathogens and potentially toxic substances; moreover, even immune cells and proteins cannot pass through the BBB. (The brain had to acquire its own backup immune system, and its functions were taken over by some neuroglial cells, whose task is to serve neurons.) Thanks to the BBB, which passes only simple nutrients and metabolic products, the brain feels almost perfectly protected from the external environment. However, many dangerous diseases (for example, cancer or Alzheimer's syndrome) arise not so much because of external pathogens, but because something begins to go wrong in the brain itself.
About ten years ago, Kullervo Hynynen from the Sunnybrook Research Center in Toronto proposed a method that could briefly open the blood-brain barrier, thereby making the brain accessible to immune proteins and drugs. This method can be called bubble-ultrasound: microscopic bubbles injected into the blood, under the influence of weak ultrasound, had to squeeze through the dense intercellular contacts of barrier cells.
It was assumed that a short-term "breakdown" of the BBB would help at least partially suppress the development of Alzheimer's disease. Beta-amyloid peptide, which destroys nerve cells, should be destroyed by microglial cells, but in Alzheimer's syndrome, when beta-amyloid becomes too much, microglial cells stop coping with it. However, after ultrasound treatment, as experiments on mice showed, microglia began to absorb bad peptides more actively, and, in addition, cognitive abilities improved in animals with Alzheimer's–like symptoms - for example, animals began to orient themselves better in space. This happened, apparently, because the antibodies that penetrated the BBB stimulated the work of glial cells.
Microbubbles from blood vessels under the influence of ultrasound increase the permeability of the blood-brain barrier, and antibodies from the blood can reach pathogenic amyloid deposits in the nervous tissue. (Drawing by Emmanuel Thevenot, Sunnybrook ResearchThe results were published by Hyunyunen and his colleagues in December last year in the journal Radiology, and just the other day another article was published in Science Translational Medicine (Gerhard Leinenga and Jurgen Gotz, Scanning ultrasound removes amyloid-b and restores memory in an Alzheimer's disease mouse model).
In it, researchers from the University of Queensland describe the modification of the ultrasound method and its successful application – however, also so far only on mice (see the press release of Alzheimer's breakthrough uses ultrasound technology). This time, ultrasound was not used to treat any specific area of the skull, but almost its entire surface. A few weeks later, mice with Alzheimer's-like symptoms were tested in three different cognitive tests, and, as it turned out, micro-bubbles with ultrasound completely restored the animals' memory. Deposits of beta-amyloid decreased by 2-5 times, and the amount of it absorbed by microglial cells increased proportionally.
Of course, there are certain doubts that the method is suitable for humans – let ultrasound work on mice, but, firstly, the human brain is simply larger, and secondly, it will be very difficult to standardize the use of ultrasound to the human blood-brain barrier. You need to know exactly how permeable it is, how it depends on the duration of treatment, whether negative side effects are possible here. On the other hand, the procedure can be scaled up in experiments with larger animals, and right now researchers are planning a series of experiments in which rabbits, goats and sheep will be used instead of rodents, and in the future it may come to monkeys.
In addition, oncologists were interested in ultrasound. Neurosurgeon Todd Mainprize and his colleagues from the University of Toronto have undertaken clinical testing of the method with the participation of cancer patients: it is assumed that an increase in the permeability of the blood-brain barrier will increase the effectiveness of chemotherapy and immunotherapy. Similar tests are also taking place in France (Treatment of brain cancer: ultrasound opens the blood–brain barrier - VM). Hopefully, the results will be encouraging, because malignant brain tumors are one of the most unpleasant types of cancer: they can not always be surgically removed, and they are difficult to treat non-operatively.
In general, the problem of the blood-brain barrier has long occupied researchers, and ultrasonic "hacking" is far from the only way to overcome it. Alternatively, we can recall the lockpick molecule, which was described in 2011 by researchers from Cornell University - it turned out to be ordinary adenosine, which opens the BBB for 18 hours. A different solution was proposed two years ago by doctors from French Hospital – they managed to slow down the development of Parkinson's disease in several patients by combining a syringe with an intracerebral implant: the device fed a neuroprotective agent directly into the brain, bypassing the blood-brain barrier.
Portal "Eternal youth" http://vechnayamolodost.ru13.03.2015