Researchers from Skoltech — a VEB.RF group institution — and their colleagues from the Institute of Cytology and Genetics of SB RAS, and other medical science centers in Russia have managed to modulate the breathing and heart rate in a mouse by wirelessly stimulating its vagus nerve. The electrical stimulation was delivered by nontoxic magnetic microparticles, which acted as tiny electrodes in the nerve tissue.
This actively researched approach is a promising alternative to surgically implanted electrodes in the brain, which are used as a last-resort option in severe treatment-resistant cases of epilepsy and Parkinson’s disease and are under investigation for dementia, chronic pain, and other neurological conditions. The study was published in Advanced Functional Materials and supported by a Russian Science Foundation grant.
Invasive as it may be, electrical brain stimulation is either known or strongly suspected to provide benefits in a wide range of neurological, movement, and psychiatric conditions, where pharmaceuticals and other conventional treatments fail and the disease is severe.
Stimulation via surgically implanted electrodes is already used to treat Parkinson’s disease, essential tremor, drug-resistant epilepsy, and obsessive-compulsive disorder. It is actively researched as a treatment for Alzheimer’s disease and other dementias, Tourette syndrome, treatment-resistant depression, substance addictions, chronic pain, and cluster headache.
“Despite the obvious benefits, when you hold one of those electrodes in your hand or better yet look at a brain scan of a patient with a five-centimeter long piece of metal in their brain, you cannot help but wonder if a less invasive alternative exists,” says study co-author Professor Gleb Sukhorukov, who heads the Center for Bio- and Medical Technologies at Skoltech. “We are working on replacing electrodes with biocompatible microparticles the size of individual neurons that could be delivered with an injection. Sure, a brain injection is still invasive, but a lot less so. And if we manage to make those particles about 10 times smaller, enhanced nasal delivery would be a possibility, too.”
While the approach itself is not new, the magnetic microparticles designed by the team have the key advantage of biocompatibility. Previously existing analogues incorporated the toxic metals cobalt or nickel. The new microparticle is free of toxic materials.
The hockey puck-shaped composite microparticles are made of a polymer called polylactic acid with many tiny rods of iron oxide incorporated in each. Despite the word “acid” in its name, degradable PLA is a solid material that looks like milky-white plastic.
The particles are manufactured by adding magnetic nanorods to a solution of polylactic acid and pouring it into microwells whose diameter corresponds to the desired particle size. The material is then crystallized (hardened) in the wells in the presence of a magnetic field, which puts all the metal rods into alignment, like many miniature compass needles. This ordering is crucial for future application.
Prepared this way, the particles then have to be delivered to the relevant brain region or peripheral nerve that is to be stimulated. As a way of testing the efficacy of the particles, the team surgically put them in contact with a mouse vagus nerve, which manages heart rate, breathing, digestion, and other involuntary functions. In actual medical applications, less invasive procedures, such as injections and enhanced nasal delivery, will be the options of choice.
Once a magnetic particle and an individual neuron are in contact (the two share the same size), activating the microagent will excite the cell, whether in the brain, the spinal cord, or a peripheral fiber. Activation is achieved via a variable magnetic field. It causes the metal rods to press against the polymer. As a piezoelectric material, polylactic acid generates electricity when subjected to mechanical stress. In the experiment, the electrical pulses produced that way were observed to affect the breathing and heart rate of the mouse.
“This is the first experiment in an animal model that demonstrates that nontoxic magnetic microparticles can modulate these involuntary processes. In the experiment, we observed an increased respiratory rate and a decreased heart rate once the activation threshold was exceeded. That said, the same approach can be used for remote activation of neural pathways in general. We plan to begin modeling specific disorders and trauma in mice this year. These will include concussion,” Sukhorukov added.
