20 March 2018

We'll go the other way

The resounding cure of paralyzed rats finally got an explanation

Daria Zagorskaya, Vesti

A few years after the return of the joy of movement to the paralyzed rats, scientists were able to understand exactly what is happening in the rodents' body.

In 2012, an international team of scientists, which included Russian neurophysiologists from the Institute of Physiology. Pavlova RAS surprised the world by putting rats with serious spinal injuries on their feet. After a course of rehabilitation using a robotic exoskeleton and electrochemical stimulation of the spinal cord, the animals not only regained control of their paralyzed limbs, but were also able to overcome obstacles, for example, climb stairs.

And only now the same team of biologists led by Gregory Courtine from the State Polytechnic School in Lausanne (EPFL) has found out how nerve signals bypass the damaged area and continue their way to the muscles of the hind legs (Programming DNA to deliver cancer drugs). Namely, in an article published in Nature Neuroscience, it is reported that researchers have observed for the first time how the brain redirects motor commands along alternative paths going to the spinal cord.

In the new work, as before, scientists used a special technique for the rehabilitation of rats with spinal cord injury, which combined electrochemical stimulation of nerve pathways and training using a kind of robotic exoskeleton. Special pharmaceutical preparations were first injected into the spinal cord of the animals, and then with the help of electrodes, stimulation was carried out below the injured area to activate the limbs.

At the beginning of therapy, rodents supported by an "intellectual" frame learned to make individual awkward movements. But after a few weeks of exercise, they could walk, swim and climb stairs without any additional stimulation.

Comparing the brains of healthy animals and paralyzed rats after rehabilitation, scientists identified an area in the brain stem that seemed to play a key role in recovery. But in order to reveal the secret, it was necessary to use complex methods of opto- and chemogenetics, which allow using light or chemical agents to activate or block certain neural circuits in transgenic animals, and thus determine their functions.

To visualize neural connections, the researchers used the latest planar illumination microscope developed by specialists of the Wyss Center for Bio- and Neuroengineering in Geneva (Wyss Center). In the images obtained with its help, the entire nervous system looked transparent, with the exception of neurons containing fluorescent protein.

The analysis showed that the miraculous healing of rats was not associated with the healing of severed nerve connections. Instead, the nervous system sent a signal bypassing alternative intact pathways.

"The brain develops new anatomical connections through areas of the nervous system that remain intact after injury," says Curtin in a press release. – The brain runs circuits from the cerebral cortex through the brainstem to the spinal cord. And with the help of a new generation of microscopy, we can explore these complex weaves in unprecedented detail."

Scientists cannot yet say for sure that similar changes will occur in the body of people who have suffered a spinal injury. But previous studies have shown that the human nervous system has even greater plasticity than that of rodents. In any case, work in this direction is actively continuing.

"Recovery is not spontaneous," says lead author of the paper, Léonie Asboth. – In order to organize new ways, the animal must undergo intensive rehabilitation therapy in any case."

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