"Long before it's in the papers"
June 01, 2012

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Rats cured of spine injury paralysis: study

June 1, 2012
Courtesy of the Ecole Polytechnique 
Fédérale de Lausanne 
and World Science staff

Us­ing chem­i­cal in­jec­tions and a spe­cial robotic de­vice, sci­en­tists say they’ve man­aged to help par­a­lyzed rats start mov­ing again—then, learn to walk and run on their own.

“Our rats have be­come ath­letes when just weeks be­fore they were com­pletely par­a­lyzed. I am talk­ing about 100 per­cent re­cu­pera­t­ion of vol­un­tary move­men­t,” ex­claimed Gré­goire Cour­tine of the Fed­er­al Pol­y­tech­nic School of Lau­sanne, lead au­thor of the stu­dy, pub­lished in the June 1 is­sue of the jour­nal Sci­ence.

The re­sults show that a sev­ered part of the spi­nal cord can make a come­back when its own “in­tel­li­gence” and re­gen­er­a­tive ca­pa­city are reawak­ened, ac­cord­ing to the re­search­ers. The stu­dy, be­gun five years ago at the Uni­vers­ity of Zu­rich, points to a pro­found change in our un­der­stand­ing of the cen­tral nerv­ous sys­tem, they added, though it’s un­clear if si­m­i­lar tech­niques could work for hu­mans.

Cour­tine and col­leagues in­jected a so­lu­tion of chem­i­cals called monoamine agonists in­to the rats. These sub­stances trig­ger cell re­sponses by at­tach­ing them­selves to mo­lec­u­lar com­plexes in cells that rec­og­nize nat­u­ral mes­sen­ger chem­i­cals—dopamine, adren­a­line, and ser­o­to­nin. The cock­tail is de­signed to re­place neu­ro­trans­mit­ters, or mes­sen­ger chem­i­cals, re­leased by the brain, then to stim­u­late nerve cells and pre­pare them to co­or­di­nate low­er body move­ment.

Five to 10 min­utes af­ter the in­jec­tion, the sci­en­tists elec­tric­ally stim­u­lated the spi­nal cord with elec­trodes im­planted in the out­er­most lay­er of the spi­nal ca­nal, called the epi­dur­al space. “This lo­cal­ized epi­dur­al stimula­t­ion sends con­tin­u­ous elec­trical sig­nals through nerve fibers to the chem­ic­ally ex­cit­ed neu­rons [nerve cells] that con­trol leg move­ment. All that is left was to in­i­ti­ate that move­men­t,” said Ru­bia van den Brand, con­tri­but­ing au­thor to the stu­dy.

In a pa­per pub­lished in the jour­nal Na­ture Neu­ro­sci­ence in 2009, Cour­tine re­ported that a stim­u­lated rat spi­nal column—sep­a­rated from the brain from the in­ju­ry down—de­vel­oped in a sur­pris­ing way: It started tak­ing over the task of mod­u­lat­ing leg move­ment, let­ting pre­vi­ously par­a­lyzed ro­dents walk, though in­vol­un­tar­ily, over tread­mills. These ex­pe­ri­ments in­di­cat­ed that the tread­mil­l’s move­ment cre­at­ed sen­so­ry feed­back that trig­gered walk­ing: the spi­nal brain took over, and walk­ing oc­curred with­out any in­put from the ac­tu­al brain. This sur­prised the re­search­ers and led them to be­lieve that only a very weak sig­nal from the brain was needed for the an­i­mals to in­i­ti­ate move­ment of their own will.

Cour­tine lat­er re­placed the tread­mill with a robotic de­vice that sup­ported the sub­jects and only came in­to play when they lost bal­ance, giv­ing them the im­pres­sion of hav­ing work­ing move­ment abil­i­ties. This en­cour­aged the rats to will them­selves to­ward a choc­o­late re­ward on the oth­er end of the plat­form, he ex­plained. “What they deemed willpower-based train­ing trans­lated in­to a four­fold in­crease in nerve fibers through­out the brain and spine,” said Ja­nine Heutschi, who al­so worked on the proj­ect.

Cour­tine calls this re­growth “new on­togeny,” a sort of du­plica­t­ion of an in­fan­t’s growth phase. The re­search­ers al­so found that newly formed nerve fibers by­passed the orig­i­nal in­ju­ry and let sig­nals from the brain reach the electrochem­ic­ally-awakened spine.

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Using chemical injections and a special robotic device, scientists say they’ve managed to help paralyzed rats start moving again—and eventually, learn to walk and run on their own. “Our rats have become athletes when just weeks before they were completely paralyzed. I am talking about 100% recuperation of voluntary movement,” exclaimed Grégoire Courtine of the Federal Polytechnic School of Lausanne, lead author of the study, published in the June 1 issue of the journal Science. The results show that a severed part of the spinal cord can make a comeback when its own “intelligence” and regenerative capacity are reawakened, according to the researchers. The study, begun five years ago at the University of Zurich, points to a profound change in our understanding of the central nervous system, they added, though it’s unclear if similar techniques could work for humans. Courtine and colleagues injected a solution of chemicals called monoamine agonists into the rats. These substances trigger cell responses by attaching themselves to molecular complexes in cells that recognize natural messenger chemicals—dopamine, adrenaline, and serotonin. The cocktail is designed to replace “neurotransmitters,” or messenger chemicals, released by the brain, then to stimulate nerve cells and prepare them to coordinate lower body movement. Five to 10 minutes after the injection, the scientists electrically stimulated the spinal cord with electrodes implanted in the outermost layer of the spinal canal, called the epidural space. “This localized epidural stimulation sends continuous electrical signals through nerve fibers to the chemically excited neurons [nerve cells] that control leg movement. All that is left was to initiate that movement,” said Rubia van den Brand, contributing author to the study. In a paper published in the journal Nature Neuroscience in 2009, Courtine reported that a stimulated rat spinal column—separated from the brain from the injury down—developed in a surprising way: It started taking over the task of modulating leg movement, letting previously paralyzed rodents walk, though involuntarily, over treadmills. These experiments indicated that the treadmill’s movement created sensory feedback that triggered walking: the spinal brain took over, and walking occurred without any input from the actual brain. This surprised the researchers and led them to believe that only a very weak signal from the brain was needed for the animals to initiate movement of their own will. Courtine later replaced the treadmill with a robotic device that supported the subjects and only came into play when they lost balance, giving them the impression of having working movement abilities. This encouraged the rats to will themselves toward a chocolate reward on the other end of the platform, he explained. “What they deemed willpower-based training translated into a fourfold increase in nerve fibers throughout the brain and spine,” said Janine Heutschi, who also worked on the project. Courtine calls this regrowth “new ontogeny,” a sort of duplication of an infant’s growth phase. The researchers also found that newly formed nerve fibers bypassed the original injury and let signals from the brain reach the electrochemically-awakened spine. injury, study reports