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Severed axons regrow to target

Scientists have met one of the long-standing challenges of regenerative medicine: For the first time, they have succeeded in coaxing an injured spinal cord to regenerate sensory axons in rats that reinnervate the specific place they would need to reach in order to regain function. Human vertebral columnImage: Gray's Anatomy, via Wikipedia However, the paper, published online in Nature Neuroscience, showed that the regenerated axons, which also formed synapses, showed little to no activity. "

By | August 2, 2009

Scientists have met one of the long-standing challenges of regenerative medicine: For the first time, they have succeeded in coaxing an injured spinal cord to regenerate sensory axons in rats that reinnervate the specific place they would need to reach in order to regain function.
Human vertebral column
Image: Gray's Anatomy, via Wikipedia
However, the paper, published online in Nature Neuroscience, showed that the regenerated axons, which also formed synapses, showed little to no activity. "I think it's impressive what they've found," said linkurl:John Houle,;http://neurobio.drexelmed.edu/houleweb/houle.html who studies regeneration after spinal cord injury at Drexel University College of Medicine in Philadelphia. However, he cautioned that the lack of physiological response from the regenerated structures left him "underwhelmed." Often, scientists researching regeneration achieve anatomical repair without physiological repair, "and then other times we see some behavioral recovery without any anatomical basis," said Houle, who was not involved in the research. For that reason, the community is still a long ways away from having any major impact on spinal cord injury. "I just think we need to be really guarded in how we talk about recovery," he told The Scientist. Regenerating axons can make potentially millions of connections, and need to reach the right targets in order to regain function. To test whether they could guide this growth to the correct spot, the researchers, led by linkurl:Mark Tuszynski;http://tuszynskilab.ucsd.edu/ and first author Laura Taylor Alto at the University of California, San Diego, made lesions in 14 rats' spinal cords two millimeters from the target site -- the nucleus gracilis in the brainstem, one of the relay stations for signals traveling from the spinal cord to the brain. The authors added a graft of autologous bone marrow stromal cells as scaffolding for the regenerating axons, and injected a lentiviral vector expressing a growth-promoting factor, neurotrophin-3 (NT-3), into the nucleus gracilis, to guide regenerating axons to that specific location. They found that new axons reinnervated the nucleus gracilis, and boosting the amount of NT-3 increased reinnervation -- to 27% of the innervation present in intact regions. The new axons "grow exactly into the right area," said study author linkurl:Armin Blesch,;http://tuszynskilab.ucsd.edu/blesch.php also at UCSD. When the researchers directed NT-3 to a different region, the axons grew in that direction. The axons that reached the nucleus gracilis formed synapses that appeared to resemble normal synapses, but showed little to no activity. The regenerating axons appeared to also have little to no myelin, which may explain the lack of synaptic activity, Blesch suggested. The findings "really show how fundamental [remyelination] is," he said, adding that he and his colleagues did not test whether myelination did, in fact, restore function. Blesch explained that he and his coauthors decided to do this experiment after previous experiments showed that regenerating axons could grow 2-3 mm following lesions. They therefore decided to figure out if axons covering that distance could reach the right target. "The next step is to see if we can get these [targeted] axons to grow longer," he said, perhaps by adding factors that counteract inhibitors to growth. The current paper "is an incremental step, and it's an important one, and it just indicates there's much more work to be done," said Houle. Correction (August 3): When originally posted, the article stated the paper was published in the current issue of Nature Neuroscience. The linkurl:article;http://www.nature.com/neuro/journal/vaop/ncurrent/abs/nn.2365.html is, in fact, an advance online publication. The Scientist regrets the error.
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[27th July 2009]*linkurl:Right on Geron;tp://www.the-scientist.com/blog/display/
[23rd January 2009]*linkurl:Neural tissue engineering;http://www.the-scientist.com/article/display/14782/
[21st June 2004]
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Avatar of: Rick Bogle

Rick Bogle

Posts: 14

August 3, 2009

The path and rate of growth of regenerating motor neurons in the cockroach. Denburg JL, Seecof RL, Horridge GA. Brain Res. 1977.\n\nNerve root 5 that supplies the coxal depressor muscles from the metathoracic ganglion in the cockroach was crushed. Regeneration of the motor neurons was studied by cutting the nerve at several distances from the crush point and introducing cobalt chloride into the cut end. The operation was followed by a lag period of about 13 days after which the axons regenerated at a rate of 0.9 mm per day. After regeneration had been completed a pattern of axon distribution was established among the nerve branches that was very similar to that found in intact, normal cockroaches. This pattern was established through an apparent directed growth of certain axons from identified cells into branch 5rl, their normal pathway. However, at the same time, radom or increased branching of other unidentified motor neurons produced some errors in the distribution of axons among the nerve branches. Eventually these errors were corrected by the degeneration of neuronal processes that did not synapse with correct target muscles. These results demonstrate the requirement for a highly specific intercellular recognition process between individual, identified motor neurons and the appropriate muscles they innervate in order to reform the original innervation pattern during regneration\n

January 10, 2010

HAPPY BELATED XMAS AND THANKS FOR TAKING TIME WITH ME,HAPPY NEW YEAR(S)TOO.

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