Broken nerves can be fixed in a flash
Posted: Fri Nov 21, 2008 1:42 am
Amazing science at work here.
http://www.newscientist.com/article/mg2 ... flash.html
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Broken nerves can be fixed in a flash
* 17 November 2008 by Alison Motluk
* Magazine issue 2682.
RATS with breathing problems caused by damage to their nerves have had normal breathing restored by bursts of visible light aimed onto the spinal cord. This achievement raises hopes that a miniature light source implanted near the spine might one day allow people with similar injuries to breathe normally.
In 2005, Ed Boyden at the Massachusetts Institute of Technology infected neurons in Petri dishes with viruses carrying the ChR2 gene, which codes for a light-sensitive protein called channelrhodopsin-2. The neurons started expressing the protein, and this allowed the researchers to use pulses of light to control when the neurons fired (Nature Neuroscience, vol 8, p 1263). "The nerve cells think they are photoreceptors," says neuroscientist Jerry Silver at Case Western Reserve University in Cleveland, Ohio.
Silver has now taken things a step further with a study to investigate how this light-operated neuronal switch might be used to restore function lost as a result of nerve damage. His team cut part way through the spinal cords of rats at the second vertebra from the top, where the neck pivots, severing the connection between the spinal cord and the nerves that control one side of the diaphragm. This prevented messages from the brain getting to the diaphragm, leaving the animals with problems breathing. Similar injuries are the leading cause of death in people with spinal cord damage.
The researchers then injected a virus containing ChR2 just below the injury. Four days later they cut into the animals again to expose the spinal cord and shone light onto the damaged section. A 1-minute sequence of half-second pulses produced some activity in the neurons, and consequently in the damaged side of the diaphragm.
The big breakthrough came when they extended the treatment to three 5-minute cycles of 1-second light pulses followed by 5 minutes of rest. "A bizarre seizure activity started," says Silver. When the seizure ended, normal breathing resumed and lasted for about a day and a half (The Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.3378-08.2008). Surprisingly, the two sides of the diaphragm were working in tandem.
In uninjured animals, the two sides are synchronised by the brain - raising the question of how they could remain in sync when the nerve to one side was still severed. Silver reckons that in his rats, the light activates a latent network of neurons that span the spinal column, allowing the two sides to communicate independently of the brain.
Boyden sees Silver's discovery as a powerful proof of principle. "It opens up the investigation on how you can recruit existing circuits to compensate for lost ones."
Silver says the light-switch technique could one day be used to treat people with breathing problems resulting from nerve damage. Patients could be given an implant that would shine light on damaged nerves, eliminating the need for repeated surgery.
Patients with breathing problems could one day be given an implant that would shine light on damaged nerves
A similar device might be used to relieve constriction of the bladder caused by nerve damage. Boyden is working on a device that would achieve this without the need to surgically expose the neurons. Samarendra Mohanty at the Beckman Laser Institute in Irvine, California, is developing an infrared light source that can be piped into nerves through fibres about 50 micrometres thick, also with the aim of activating nerves remotely.
http://www.jneurosci.org/cgi/content/ab ... 8/46/11862
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The Journal of Neuroscience,
November 12, 2008,
28(46):11862-11870; doi:10.1523/JNEUROSCI.3378-08.2008
Light-Induced Rescue of Breathing after Spinal Cord Injury
Warren J. Alilain,1 Xiang Li,1 Kevin P. Horn,1 Rishi Dhingra,2 Thomas E. Dick,1,2 Stefan Herlitze,1 and Jerry Silver1
1Department of Neurosciences and 2Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
Correspondence should be addressed to Dr. Jerry Silver, Department of Neurosciences, Case Western Reserve University School of Medicine, Room E-658, 2109 Adelbert Road, Cleveland, OH 44106. Email: jxs10@case.edu
Paralysis is a major consequence of spinal cord injury (SCI). After cervical SCI, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. Expression of channelrhodopsin-2 (ChR2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. We hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express ChR2, photostimulation would restore respiratory motor function in cervical SCI adult animals. Here we show that light activation of ChR2-expressing animals was sufficient to bring about recovery of respiratory diaphragmatic motor activity. Furthermore, robust rhythmic activity persisted long after photostimulation had ceased. This recovery was accomplished through a form of respiratory plasticity and spinal adaptation which is NMDA receptor dependent. These data suggest a novel, minimally invasive therapeutic avenue to exercise denervated circuitry and/or restore motor function after SCI.
Key words: spinal cord injury; paralysis; respiration; motor neuron; plasticity; NMDA receptor; kindling
http://www.newscientist.com/article/mg2 ... flash.html
=================================================
Broken nerves can be fixed in a flash
* 17 November 2008 by Alison Motluk
* Magazine issue 2682.
RATS with breathing problems caused by damage to their nerves have had normal breathing restored by bursts of visible light aimed onto the spinal cord. This achievement raises hopes that a miniature light source implanted near the spine might one day allow people with similar injuries to breathe normally.
In 2005, Ed Boyden at the Massachusetts Institute of Technology infected neurons in Petri dishes with viruses carrying the ChR2 gene, which codes for a light-sensitive protein called channelrhodopsin-2. The neurons started expressing the protein, and this allowed the researchers to use pulses of light to control when the neurons fired (Nature Neuroscience, vol 8, p 1263). "The nerve cells think they are photoreceptors," says neuroscientist Jerry Silver at Case Western Reserve University in Cleveland, Ohio.
Silver has now taken things a step further with a study to investigate how this light-operated neuronal switch might be used to restore function lost as a result of nerve damage. His team cut part way through the spinal cords of rats at the second vertebra from the top, where the neck pivots, severing the connection between the spinal cord and the nerves that control one side of the diaphragm. This prevented messages from the brain getting to the diaphragm, leaving the animals with problems breathing. Similar injuries are the leading cause of death in people with spinal cord damage.
The researchers then injected a virus containing ChR2 just below the injury. Four days later they cut into the animals again to expose the spinal cord and shone light onto the damaged section. A 1-minute sequence of half-second pulses produced some activity in the neurons, and consequently in the damaged side of the diaphragm.
The big breakthrough came when they extended the treatment to three 5-minute cycles of 1-second light pulses followed by 5 minutes of rest. "A bizarre seizure activity started," says Silver. When the seizure ended, normal breathing resumed and lasted for about a day and a half (The Journal of Neuroscience, DOI: 10.1523/JNEUROSCI.3378-08.2008). Surprisingly, the two sides of the diaphragm were working in tandem.
In uninjured animals, the two sides are synchronised by the brain - raising the question of how they could remain in sync when the nerve to one side was still severed. Silver reckons that in his rats, the light activates a latent network of neurons that span the spinal column, allowing the two sides to communicate independently of the brain.
Boyden sees Silver's discovery as a powerful proof of principle. "It opens up the investigation on how you can recruit existing circuits to compensate for lost ones."
Silver says the light-switch technique could one day be used to treat people with breathing problems resulting from nerve damage. Patients could be given an implant that would shine light on damaged nerves, eliminating the need for repeated surgery.
Patients with breathing problems could one day be given an implant that would shine light on damaged nerves
A similar device might be used to relieve constriction of the bladder caused by nerve damage. Boyden is working on a device that would achieve this without the need to surgically expose the neurons. Samarendra Mohanty at the Beckman Laser Institute in Irvine, California, is developing an infrared light source that can be piped into nerves through fibres about 50 micrometres thick, also with the aim of activating nerves remotely.
http://www.jneurosci.org/cgi/content/ab ... 8/46/11862
========================================================
The Journal of Neuroscience,
November 12, 2008,
28(46):11862-11870; doi:10.1523/JNEUROSCI.3378-08.2008
Light-Induced Rescue of Breathing after Spinal Cord Injury
Warren J. Alilain,1 Xiang Li,1 Kevin P. Horn,1 Rishi Dhingra,2 Thomas E. Dick,1,2 Stefan Herlitze,1 and Jerry Silver1
1Department of Neurosciences and 2Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106
Correspondence should be addressed to Dr. Jerry Silver, Department of Neurosciences, Case Western Reserve University School of Medicine, Room E-658, 2109 Adelbert Road, Cleveland, OH 44106. Email: jxs10@case.edu
Paralysis is a major consequence of spinal cord injury (SCI). After cervical SCI, respiratory deficits can result through interruption of descending presynaptic inputs to respiratory motor neurons in the spinal cord. Expression of channelrhodopsin-2 (ChR2) and photostimulation in neurons affects neuronal excitability and produces action potentials without any kind of presynaptic inputs. We hypothesized that after transducing spinal neurons in and around the phrenic motor pool to express ChR2, photostimulation would restore respiratory motor function in cervical SCI adult animals. Here we show that light activation of ChR2-expressing animals was sufficient to bring about recovery of respiratory diaphragmatic motor activity. Furthermore, robust rhythmic activity persisted long after photostimulation had ceased. This recovery was accomplished through a form of respiratory plasticity and spinal adaptation which is NMDA receptor dependent. These data suggest a novel, minimally invasive therapeutic avenue to exercise denervated circuitry and/or restore motor function after SCI.
Key words: spinal cord injury; paralysis; respiration; motor neuron; plasticity; NMDA receptor; kindling