Hybrid tunnel may help guide severed nerves back to health

Building a tunnel made up of both hard and soft materials to guide the reconnection of severed nerve endings may be the first step toward helping patients who have suffered extensive nerve trauma regain feeling and movement, according to a team of biomedical engineers.

"Nerve injury in both central nervous system and peripheral nervous system is a major health problem," said Mohammad Reza Abidian, assistant professor of biomedical engineering, Penn State. "According to the National Spinal Cord Injury Statistical Center, there are approximately 290,000 individuals in the US who suffer from spinal cord injuries with about 12,000 new injuries occurring each year."

Spontaneous nerve regeneration is limited to small lesions within the injured peripheral nerve system and is actively suppressed within central nervous system. When a nerve in the peripheral nervous system is cut slightly, nerve endings can regenerate and reconnect. However, if the distance between the two endings is too far, the growth can go off course and fail to connect.

The researchers, who published their results in the current issue of Advanced Healthcare Materials, developed a novel hybrid conduit that consisted of a soft material, called a hydrogel, as an external wall along with an internal wall made of an electrically-active conducting polymer to serve as a tunnel that guides the regrowth and reconnection of the severed nerve endings.

Abidian said that the method could offer advantages over current surgeries that are used to reconnect severed nerves.

"Autografts are currently the gold standard for bridging nerve gaps," said Abidian. "This is an operation that takes the nerve from another portion of the body — for instance — from a tendon, and then it is grafted onto the injured nerve."

However, the operation can be painful and there are often mismatches in size between the severed nerve endings and the new grafted portion of the nerve, Abidian said.

A step forward in regenerating and repairing damaged nerve cells

A team of IRCM researchers, led by Dr. Frédéric Charron, recently uncovered a nerve cell’s internal clock, used during embryonic development. The discovery was made in collaboration with Dr. Alyson Fournier’s laboratory at the Montreal Neurological Institute. Published in the prestigious scientific journal Neuron, this breakthrough could lead to the development of new tools to repair and regenerate nerve cells following injuries to the central nervous system.

Researchers in Dr. Charron’s laboratory study neurons, which are the nerve cells that make up the central nervous system (brain and spinal cord). They want to better understand how neurons navigate through the developing embryo to arrive at their correct destination.

“To properly form neural circuits, developing axons (long extensions of neurons that form nerves) follow external signals to reach the right targets,” says Dr. Frédéric Charron, Director of the Molecular Biology of Neural Development research unit at the IRCM. “We discovered that nerve cells also have an internal clock, which changes their response to external signals as they develop over time.”

For this research project, IRCM scientists focused on the Sonic Hedgehog (Shh) protein, which gives cells important information for the embryo to develop properly and plays a critical role in the development of the central nervous system.

“It is known that axons follow the Shh signal during their development,” explains Dr. Patricia Yam, research associate in Dr. Charron’s laboratory and first author of the study. “However, axons change their behaviour once they reach this protein, and this has been a mystery for the scientific community. We found that a nerve cell’s internal clock switches its response to external signals when it reaches the Shh protein, at which time it becomes repelled by the Shh signal rather than following it.”

“Our findings therefore showed that more than one system is involved in directing axon pathfinding during development,” adds Dr. Yam. “Not only do nerve cells respond to external signals, but they also have an internal control system. This discovery is important because it offers new possibilities for developing techniques to regenerate and repair damaged nerve cells. Along with trying to modify external factors, we can now also consider modifying elements inside a cell in order to change its behaviour.”

Worm Regeneration May Lend A Hand in Human Healing

About the size of toenail clippings, planarians are freshwater flatworms that can re-form from tiny slivers. This feature not only lets them repair themselves, but it lets them reproduce by breaking apart and then creating new worms.   

Here are two other important features: More than half of planarian genes have parallels in people, and some of their basic physiological systems operate like ours. By studying how these features behave as the worms regenerate, scientists might move one step closer to learning how to generate or regenerate human tissue and cells, such as insulin-producing cells for people with diabetes or nerve cells for patients with spinal cord injuries.

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Inflammation for Regeneration

The secret to zebrafish’s remarkable capacity for repairing their brains is inflammation, according to a report published online in Science. Neural stem cells in the fish’s brains express a receptor for inflammatory signaling molecules, which prompt the cells to multiply and develop into new neurons.

“This is a very interesting paper,” said Guo-li Ming, a professor of neurology and neuroscience at The Johns Hopkins University in Baltimore, who was not involved in the study. “It is well known that fish have this ability to self-repair, and this paper provides a mechanism,” she said.

Zebrafish, like many other vertebrates, are able to regenerate a variety of body tissues, including their brains. In fact, said Michael Brand, a professor of developmental genetics at the Technische Universität in Dresden, Germany, “mammals are the ones that seem to have lost this ability—they are kind of the odd ones out.” Given the therapeutic potential of neuron regeneration for patients with brain or spinal injuries, “we’d like to figure out if we can somehow reactivate this potential in humans,” Brand said.

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Researchers Find Regenerated Lizard Tails Are Different From Originals

Just because a lizard can grow back its tail, doesn’t mean it will be exactly the same. A multidisciplinary team of scientists from the University of Arizona and Arizona State University examined the anatomical and microscopic make-up of regenerated lizard tails and discovered that the new tails are quite different from the original ones. The findings are published in a pair of articles featured in a special October edition of the journal, The Anatomical Record.

“The regenerated lizard tail is not perfect replica,” said Rebecca Fisher, an associate professor at the UA College of Medicine-Phoenix. “There are key anatomical differences including the presence of a cartilaginous rod and elongated muscle fibers spanning the length of the regenerated tail.”

Researchers studied the regenerated tails of the green anole lizard (Anolis carolinensis), which can lose its tail when caught by a predator and then grow it back. The new tail had a single, long tube of cartilage rather than vertebrae, as in the original. Also, long muscles span the length of the regenerated tail compared to shorter muscle fibers found in the original.

"These differences suggest that the regenerated tail is less flexible, as neither the cartilage tube nor the long muscle fibers would be capable of the fine movements of the original tail, with its interlocking vertebrae and short muscle fibers," said Fisher, who also is an associate professor in the School of Life Sciences at ASU. "The regrown tail is not simply a copy of the original, but instead is a replacement that restores some function."

Study Suggests Immune System Can Boost Nerve Regrowth

Modulating immune response to injury could accelerate the regeneration of severed peripheral nerves, a new study in an animal model has found. By altering activity of the macrophage cells that respond to injuries, researchers dramatically increased the rate at which nerve processes regrew.

Influencing the macrophages immediately after injury may affect the whole cascade of biochemical events that occurs after nerve damage, potentially eliminating the need to directly stimulate the growth of axons using nerve growth factors. If the results of this first-ever study can be applied to humans, they could one day lead to a new strategy for treating peripheral nerve injuries that typically result from trauma, surgical resection of tumors or radical prostectomy.

“Both scar formation and healing are the end results of two different cascades of biological processes that result from injuries,” said Ravi Bellamkonda, Carol Ann and David D. Flanagan professor in the Wallace H. Coulter Department of Biomedical Engineering and member of the Regenerative Engineering and Medicine Center at Georgia Tech and Emory University. “In this study, we show that by manipulating the immune system soon after injury, we can bias the system toward healing, and stimulate the natural repair mechanisms of the body.”

Beyond nerves, researchers believe their technique could also be applied to help regenerate other tissue – such as bone. The research was supported by the National Institutes of Health (NIH), and reported online Sept. 26, 2012, by the journal Biomaterials.

Understanding how salamanders grow new limbs provides insights into the potential of human regenerative medicine

By studying a real lizard-like amphibian, which can regenerate missing limbs, the Salk researchers discovered that it isn’t enough to activate genes that kick start the regenerative process. In fact, one of the first steps is to halt the activity of so-called jumping genes.

In research published August 23 in Development, Growth & Differentiation, and July 27 in Developmental Biology, the researchers show that in the Mexican axolotl, jumping genes have to be shackled or they might move around in the genomes of cells in the tissue destined to become a new limb, and disrupt the process of regeneration.

They found that two proteins, piwi-like 1 (PL1) and piwi-like 2 (PL2), perform the job of quieting down jumping genes in this immature tadpole-like form of a salamander, known as an axolotl - a creature whose name means water monster and who can regenerate everything from parts of its brain to eyes, spinal cord, and tail.

"What our work suggests is that jumping genes would be an issue in any situation where you wanted to turn on regeneration," says the studies’ senior author, Tony Hunter, a professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center.