Stanford University School of Medicine scientists have developed a non-invasive remedy for medication in the brain for a few millimeters of the desired point.
The method used by rats uses ultrasonic therapy molecules that are impregnated from the nanoparticle "cage" which is impregnated in the blood vessel.
Researchers have shown that the pharmacological activity of the drug may be released from pharmacologically active quantities from the cage that may occur in a small part of the rats brain, aimed at ultrasonic node beam. Drugs went immediately to work, reducing the nervous activity target area – but only when the ultrasonic device was active and only if the ultrasound intensity exceeded a certain threshold. By changing the strength and duration of the rays, investigators could improve nervous inhibition.
Although the drug used in this study was a prophotophilia, the hospital used anesthetic, in principle, the same approach could work for many drugs that differ widely from pharmacologic activities and psychiatric applications and some chemotherapeutic drugs to combat cancer.
The researchers may observe the effects of drugs in the lower regions of the brain in areas where they have been targeted, said Ragh Haran, doctor of medicine, doctor, neuroordinology assistant. Thus, researchers would be able to live without different connections between different brain schemes.
The paper published on the results of the study was published on November 7 Neuron. Airan is the senior author. The leading author is to share Jeffrey Wang, MD-PhD program student and postdocentric scientist Muna Aryal, PhD.
The related technology, known as Opopenetics, was pioneered by Carl Déserotte, MD, PhD, Stanford Professor Bioengineering, Psychiatry and Behavioral Sciences, according to which Airan completed Doctor's Doctor's work a decade ago, providing invasive genes to use the vulnerable classes of vulnerable classes to accurate experimental manipulation. Airan's approach is to use non-invasive pharmacological methods to achieve similar control of nervous activity.
"This important work suggests that the sensitivity of ultrasound drugs seems to be necessary through the intensive brain function of the brain brain," says Dyseroty, who is not involved in the study. "Strong new techniques can be used to test optogenetically inspired ideas, originally from rodents research, large animals – and possibly soon in clinical trials."
"We are optimistic"
The new technology can not only achieve achievements in neuroscientist research, but quickly transfers to clinical practice. "Although this research was conducted in rats, each component of our nanopartol complex was approved by the Food and Drug Administration for at least human use of the investigation and focused on clinical procedures of ultrasound Stenford," he said. "So we are optimistic about the translating potential of these procedures."
Intensity intensity, high intensity ultrasound approval, which is intended for ablation or intentional destruction of certain tissues, including a part of the central brain structure called the thalamus, known as the essential tremor, is used for imaging body tissues.
For new research, we call "ultrasonic device", "Airan." Ultrasonic intensity used in these experiments was about 1/10 to 1/100 intensive use in clinical ablation procedures. Which is aimed at It is enough time to increase the brain tissue to increase the pulp.The experimental protocol has revealed several cases of exposure to the tissue damage.
The nanoparticles that were airborne for a few years were biomontoperative, biodegradable, liquid-filled areas with a diameter of 400 nanometers (about 15 million wide). Their surfaces are composed in copolymer matrix where the selected drug is stored. Approximately 3 million molecules of drugs usually dot the surface of one of these nanoparticles.
Each nanopartacot contains a substance called perfluorocarbon. With the right frequency of the ultrasound waves, this liquid core starts to shake and expose the coverage of the copper matrix surface, which is free to remove the molecules. Propopolis, as well as all psychoactive drugs, can be easily applied to a different blood cell brain barrier. But this threshold was overcome by the brain tissue quickly, so that he would never get more than half a millimeter capillary where he was released.
Airan and his colleagues injected these particles intravenously into experimental rats and studied the attention of ultrasound potential targeted drug delivery.
Initially, they are measured in the nerve cells' activity of the visual cortex, the area behind the brain, which is activated in the visual stimuli, in response to the flashes of light aiming at the rats & # 39; eyes. Focusing on ultrasonic rays on the brain area, they were watching electric activity that would be redistributed, while the beam was shifted and shut down after about 10 seconds from the device. In the electric curtain electric activity, which implies an anesthetic release, it is more pronounced to increase the intensity of ultrasound and not all cases when the rats were drug-free nanoparticles.
In contrast, the function of the motor cortex, the brain area that is not involved in vision, in terms of light flashes, was not reduced when the ultrasonic was used. But the ultrasound aimed at the side of the visual cortex of the genital nucleus, the brain area that delivers visual information visually, reduces the electrical activity during the visual cortex. It has shown that the proportion of the release of one brain structure may be the second effect of the second, remote region making means of that structure.
Brainwide metabolic response
Next, the Airan team monitors the brain metabolic reaction focusing on ultrasound analysis that absorbs the use of postostone emission tomography that allows the metabolism of the glucose-glucose radioactive analogy in the brain's main energy source – rats. When the injected nanoparticles were blanks, there was no ultrasonic exception. But the metabolism decreased by the proportion of nanoparticles, which means that the nervousness of the activity in these ultrasound regions is reduced. This suppression increases with ultrasound intensity. The ultrasonic level crash was marked by selectively reduced activity in distant brain regions, known as ultrasonic emissions.
"We hope this technology will utilize the non-invasive forecasting of the results of excise or inactivation of specific small volume brain tissue patients in the planned neurosurgery," said Airan. "Increasing the inactive or small size tissue will achieve the desired effect – for example, stopping epileptic backward activity? Will any unusual side effect affect?"
Other training co-authors are postdoctoral scholar Qian Zhong, PhD and medical student Daivik Vyas.
The work was funded by the National Institutes of Health (grants RF1MH114252 and U54CA199075), the Stanford Center of Cancer Nanotechnology Excellence, the American Society of Neuroordinology Foundation, Wallace Hall Cultural Foundation, Danny Foundation and Wu Sky Neuroscience Institute.
Stanford's office technology license has filled up patent applications for intellectual property related to new technology.
The Stanford Radiology Department also supported the work.