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| Rapid Nerve Regeneration In Mammals |
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| SciMed - Healthcare | |||
| TS-Si News Service | |||
| Sunday, 05 February 2012 16:00 | |||
Austin, TX, USA. A new procedure can partially restore severed nerves within days and often largely restore them within two to four weeks, potentially aiding patient recovery from injury or organ transplantation.The science team is conducting studies to obtain approval for the start of clinical trials. The team used a technique similar to that used by many invertebrates to repair damage to nerve axons. They studied the mechanisms all animal cells use to repair damage to their membranes and focused on invertebrates, which use a cellular mechanism that has a superior ability to regenerate nerve axons compared to mammals. An axon is a long extension arising from a nerve cell body that communicates with other nerve cells or with muscles. Two papers present the research findings in the Journal of Neuroscience Research. [C1,C2]![]() George Bittner, PhD, is a Professor in Neurobiology at the School of Biological Sciences, University of Texas at Austin.This research is based on a discovery by George Bittner from the University of Texas at Austin. He found that nerve axons of invertebrates which have been severed from their cell body do not degenerate within days, as happens with mammals, but can survive for months, or even years. Bitner says if the procedure is "... further developed in clinical trials this approach would be a great advance on current procedures that usually imperfectly restore lost function within months at best." The severed proximal nerve axon in invertebrates can also reconnect with its surviving distal nerve axon to produce much quicker and much better restoration of behavior than occurs in mammals. "Severed invertebrate nerve axons can reconnect proximal and distal ends of severed nerve axons within seven days, allowing a rate of behavioral recovery that is far superior to mammals," said Bittner. "In mammals the severed distal axonal stump degenerates within three days and it can take nerve growths from proximal axonal stumps months or years to regenerate and restore use of muscles or sensory areas, often with less accuracy and with much less function being restored." The team used rats as an experimental model to demonstrate how severed nerve axons can be repaired. They repaired severed sciatic nerves in the upper thigh, with results showing that rats were able to use their limb within a week and had much function restored within 2 to 4 weeks, in some cases to almost full function. "Without our procedure, the return of nearly full function rarely comes close to happening," said Bittner. "The sciatic nerve controls all muscle movement of the leg of all mammals and this new approach to repairing nerve axons could almost-certainly be just as successful in humans." To explore the long term implications and medical uses of this procedure, MD's and other scientist-collaborators at the Harvard Medical School and Vanderbilt Medical School and Hospitals are conducting studies to obtain approval to begin clinical trials. "We believe this procedure could produce a transformational change in the way nerve injuries are repaired," concluded Bittner. Citations[C1] Rapid, effective, and long-lasting behavioral recovery produced by microsutures, methylene blue, and polyethylene glycol after completely cutting rat sciatic nerves. G.D. Bittner, C.P. Keating, J.R. Kane, J.M. Britt, C.S. Spaeth, J.D. Fan, A. Zuzek, R.W. Wilcott, W.P. Thayer, J.M. Winograd, F. Gonzalez-Lima, T. Schallert. Journal of Neuroscience Research 2012. doi:10.1002/jnr.23023
Abstract Behavioral function lost in mammals (including humans) after peripheral nerve severance is slowly (weeks to years) and often poorly restored by 1–2-mm/day, nonspecifically directed outgrowths from proximal axonal stumps. To survive, proximal stumps must quickly repair (seal) plasmalemmal damage. We report that, after complete cut- or crush-severance of rat sciatic nerves, morphological continuity, action potential conduction, and behavioral functions can be consistently (>98% of trials), rapidly (minutes to days), dramatically (70–85% recovery), and chronically restored and some Wallerian degeneration prevented. We assess axoplasmic and axolemmal continuity by intra-axonal dye diffusion and action potential conduction across the lesion site and amount of behavioral recovery by Sciatic Functional Index and Foot Fault tests. We apply well-specified sequences of solutions containing FDA-approved chemicals. First, severed axonal ends are opened and resealing is prevented by hypotonic Ca2+-free saline containing antioxidants (especially methylene blue) that inhibit plasmalemmal sealing in sciatic nerves in vivo, ex vivo, and in rat B104 hippocampal cells in vitro. Second, a hypotonic solution of polyethylene glycol (PEG) is applied to open closely apposed (by microsutures, if cut) axonal ends to induce their membranes to flow rapidly into each other (PEG-fusion), consistent with data showing that PEG rapidly seals (PEG-seals) transected neurites of B104 cells, independently of any known endogenous sealing mechanism. Third, Ca2+-containing isotonic saline is applied to induce sealing of any remaining plasmalemmal holes by Ca2+-induced accumulation and fusion of vesicles. These and other data suggest that PEG-sealing is neuroprotective, and our PEG-fusion protocols that repair cut- and crush-severed rat nerves might rapidly translate to clinical procedures.Keywords: axotomy, nerve regeneration, nerve repair. [C2] Cellular mechanisms of plasmalemmal sealing and axonal repair by polyethylene glycol and methylene blue. C.S. Spaeth, T. Robison, J.D. Fan, G.D. Bittner. Journal of Neuroscience Research 2012. doi:10.1002/jnr.23022
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| Last Updated on Sunday, 05 February 2012 15:58 |



Austin, TX, USA. A new procedure can partially restore severed nerves within days and often largely restore them within two to four weeks, potentially aiding patient recovery from injury or organ transplantation.
axon
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