Imagine repairing injured spinal cords or brains. Many may relegate this idea to the realms of science fiction yet researchers around the world continue to strive for this goal. They have developed and tested ways to rebuild the damage nervous system and bring back proper function. Some have even shown success in the lab.
One such method was published earlier this year, http://www.jneurosci.org/content/36/3/979.long when a Quebec group of scientists found a way to improve neural repair using what would best be described as microsurgery. Using a combination of microtools – and indeed nanotools – these researchers have found they can mechanically control the regeneration process and improve the likelihood of proper neural function after injury.
The process wasn’t easy as it required some of the most sophisticated techniques available with names such as micromanipulation, microfabrication, and atomic force microscopy, which can visualize areas as small as 10 billionth of a metre http://www.charfac.umn.edu/instruments/afm_introduction.pdf. The team also had to rely on research stemming back almost thirty years in order to make it work. All in all, the process represented decades of trial and error to reach this pivotal stage.
The method itself was developed in several steps the first of which was the requirement of actual neurons, the building blocks of the nervous system. To do this, the team took rat neurons from the embryonic hippocampus and grew them in the lab. But unlike the petri dishes commonly seen, these neurons were grown in small compartments known as microfluidic chambers. The small volume would allow for individual observation and manipulation of the neurons. After two to three weeks, the neurons were ready for the next step.
Using an atomic force microscope, the team attempted to add beads to the neurons. These beads were coated with a chemical known as poly-D-lysine. The team had found several years earlier http://www.jneurosci.org/content/29/40/12449.full this molecule could help neurons attach to one another and develop the most important part of function, the synapse. If the team were correct, adding the bead would help to promote generation of neural signals.
But the bead also served another purpose. After attaching the particle to a number of neurons, the team could stretch the bundle. This would force the neurons to elongate and form neurites. This was a tricky step as too much pressure risked harming the cells themselves. In addition, the tensile strength of the neuron bundle had to be taken into consideration in terms of the distance pulled. Yet the group figured out the mechanics and found they could extend a neuron close to a millimetre in length. While this may seem quite small, in terms of nervous system repair, it represents a significant distance.
The next stage required the merging of two bundles of neurons to see if those synapses would form and connections would be made. Incredibly, within 30 minutes, a connection was established meaning they could not only culture the elongated neurons but also help them form proper neural links with a target neuron. An examination of the biology of the connections showed they were just as good as those formed naturally.
While the process worked, there was still one important requirement of this new linkage. It had to be able to send an electrochemical signal. After all, without the ability to transmit, the connection would be worthless. When the tests were performed, there was no need for concern. The neurites could fire a signal and it would be picked up and transmitted by other neurons. The effect was almost the same as two neurons connected through natural growth.
The immediate results of the experiment reveal neurons can be manipulated to elongate and also form connections with other neurons. That in itself is an incredible achievement. Yet, in terms of spinal cord and brain repair, this represents a possible novel direction for regenerative therapy. The method may be able to help deal with the formation of neural scar tissue, which is known to halt proper signalling. In addition, the length of the neurite could help to cover more distance making the potential for larger scale repair more effective. However, these options are still years away as technology needs to be able to expand from the microfluidic chamber to larger biological entities.
There is, however, a more immediate application of this research in the form of bio-inorganic networks. Using this method, a brain-machine interface may be possible to better track the activity of cerebral cells. This could provide stronger information on the workings of the brain.
But even more impressive is the possibility of bringing another science fiction staple to reality in the form of a standalone artificial nervous system. Though not possible for human analyses, the team believes it could replicate a neurological model organism such as Caenorhabditis elegans, which only has 300 neurons. Should this be achieved, the development of larger synthetic neural networks may be eyed.
Magdesian MH, Lopez-Ayon GM, Mori M, Boudreau D, Goulet-Hanssens A, Sanz R, Miyahara Y, Barrett CJ, Fournier AE, De Koninck Y, Grütter P. Rapid Mechanically Controlled Rewiring of Neuronal Circuits. J Neurosci. 2016 Jan 20;36(3):979-87. doi: 10.1523/JNEUROSCI.1667-15.2016.
Text by Jason Tetro, for CAN-ACN