5 replies to this topic

[Lazarus Long]

Here is an example of state of the art research into exactly what we need to be watching. [ph34r]

http://www.nature.co.../020819-11.html

New nerves from old
Brain cells stimulated to repair stroke damage.
23 August 2002
HELEN PEARSON


Nerve cells in the hippocampus.
© SPL

Researchers have prompted mouse brains to replace nerve cells that were killed by stroke. The discovery raises hopes that drugs could trigger brain regeneration after damage or disease.

Using a mix of two standard serums, Masato Nakafuku of Japan Science and Technology Corporation and his group stimulated new nerve cells to grow in the animals' injured hippocampus, a region involved in storing memories1. The mice did not develop some of the learning difficulties usually associated with such an injury.

Researchers had assumed that the brain was unable to repair these cells, called pyramidal neurons. Patients who suffer stroke in this area have severe and irreversible memory problems.

"It's really quite remarkable," says Sally Temple, who studies nerve regeneration at Albany Medical College in New York. Temple warns that the results need to be repeated before she is fully convinced.

The findings add to growing evidence that treatments might one day coax people's brains into repairing themselves after stroke, Parkinson's disease or other disorders. "I'm extremely confident," says neuroscientist Steven Goldman of Cornell University in New York.

Got a nerve

Several areas of the adult brain spontaneously make new cells throughout life. Recently, researchers have begun to alter the type or number of new cells using certain growth promoters.

Hippocampal pyramidal neurons, however, were thought unable to regenerate. "It's surprising," says Goldman, "but I don't think anyone had bothered to look."

Nakafuku's team starved mice of oxygen, damaging their brains. Then they infused the animals' brains for three days with two proteins that trigger cell division. They found that cells outside the hippocampus made new nerve cells that migrated into the damaged area, and appeared to form normal connections with other cells.

It is unlikely that the same serums could be used as human drugs, however, as they could trigger other cells into becoming tumours. Researchers will need to find new drugs that stimulate cells to make very specific cell types that travel to a damaged area. They also have to work out an efficient way to deliver these drugs to brain cells. This work is "at a pretty primitive stage", says Goldman.


References
Nakatomi, H. et al. Regeneration of hippocampal pyramidal neurons after ischaemic brain injury by recruitment of endogenous neural progenitors. Cell, 110, 429 - 441, (2002).

[Bruce Klein]

Researchers have prompted mouse brains to replace nerve cells that were killed by stroke. The discovery raises hopes that drugs could trigger brain regeneration after damage or disease...

Researchers had assumed that the brain was unable to repair these cells, called pyramidal neurons. Patients who suffer stroke in this area have severe and irreversible memory problems.

"It's really quite remarkable," says Sally Temple, who studies nerve regeneration at Albany Medical College in New York.

-- very cool, you're exactly right.. this is where we need to be looking. This is something we can actually do now while we're waiting for AI to catch up.

[Bruce Klein]

-- Here's another article along the same lines... I didn't know they were actually this far into this...

Life and Death in the 21st Century:
Living Forever
BBC2 8:00pm Tuesday 4th January 2000

Full Article

Excerpt:

NARRATOR: In Pittsburgh doctors are taking the first step into the future. They are beginning to exploit the potential of embryonic stem cells to regenerate our bodies. They’re using stem cells taken from a teratocarcinoma to treat people whose brains have been damaged by a stroke. Don Fitch is one such guinea-pig.

DON FITCH: I was a welder and fitter burning and welding and fitting. I dealt mostly with metal all my life. When I first had a stroke I couldn’t do anything, I was in hospital, couldn’t get out of bed, couldn’t do nothing.

MAN: OK, try and lift your hand off the bed. Can you do that? Do it?

DON FITCH: No.

MAN: OK.

DON FITCH: The hurt and, and disappointment and so on is so profound that it’s really hard to explain to anybody you know how bad it is ‘cos I just can’t imagine anything being much worse you know.

NARRATOR: Scientists decided to try an experiment. They took stem cells from a teratocarcinoma that had spontaneously created brain cells – neurones. These neurones were collected, frozen and in an extraordinary operation they were put inside Don Fitch’s brain.

(ACTUALITY OPERATION CHAT)

NARRATOR: The hope was that they’d graft themselves onto his existing brain cells and grow helping to reconnect the neural pathways that had been damaged by the stroke.

DR DOUGLAS KONDZIOLKA (University of Pittsburgh Medical Centre): The procedure went very well. He was in the hospital, you know, just one day and during that procedure a small hole was made in the top of his head.

SURGEON: How you doing there Mr. Fitch, OK.

DON FITCH: I’m fine, yeah.

SURGEON: That’s excellent.

DOUGLAS KONDZIOLKA: And using a special guiding system and a CT scan we targeted an area of the brain to implant the neurones and these were implanted through a canular. Canular removed, sewn up and he went home the next day and then we started the process of let’s see what happens to him, which is really the experimental phase of the procedure.

SURGEON: Right now we’ll see you a minute.

DON FITCH: You don’t feel no pain so, it’s OK and, and actually I’m probably a crazy person in that way. My wife could tell you I always like hospitals and I’m not afraid of them, I went to heart surgery and all that and I kind of enjoy going to it. I don’t know why.

DOUGLAS KONDZIOLKA: We’re interested in two things with him. One was this safe, how, you know how was he doing generally, and did he begin to notice anything or did the test show any changes? So he’s been in this evaluation phase over the last year.

NARRATOR: Don Fitch’s operation seems to have made a difference. The new neurones from the teratocarcinoma have slowly begun to mend the neural pathways in his brain.

DON FITCH: My arm was completely dead. I had feeling in it. I could feel if you touched me, but it did, actually it didn’t feel like the arm was there you know, like now more than I can demonstrate to you how I can use it, I don’t have that much, but boy it feels so much different. I can feel like right now I can feel the muscle in my arm. I’ve got a lot more movement in the shoulder, that’s for sure. I can rotate it, I can do a lot that I couldn’t do before and actually I’m starting to be able to get this arm to come up.

NARRATOR: Scientists are only at the beginning of making this concept work, but if it does work it could be a key breakthrough, not just for people like Don Fitch, but for those who seek immortality because it means the idea of using embryonic stem cells to rebuild our ageing bodies might really work. The idea that embryonic stem cells will one day give us full body regeneration has become a growing fantasy.

[Lazarus Long]

And for the next trick...

Gene Switching [!]
http://news.bbc.co.u...lth/2262217.stm

Monday, 16 September, 2002, 23:03 GMT 00:03 UK
Gene swap 'reverses' muscular dystrophy


Scientists were able to replace a defective gene

Scientists have managed for the first time to improve muscle function in mice with muscular dystrophy by using a type of gene therapy.
While there are hopes that this will one day translate into effective treatments for humans, experts have warned against over-optimism.

Muscular dystrophy is a genetic disorder which progressively weakens the muscles.

The body cannot produce a vital chemical called dystrophin, which helps keep muscles structurally strong.

The most common form, Duchenne muscular dystrophy, affects one in every 3,500 boys born in the UK.

This involves virtually every muscle in the body, and the cumulative damage means that most die before the age of 25.

Gene swap

Gene therapy centres on replacing the faulty gene responsible for dystrophin production with another which should work normally.

In the latest experiments, a modified common cold virus was used to "infect" muscles and swap the bad gene for the correct version.

The scientists managed to insert the entire dystrophin gene - previously thought too large to be transported this way.

Their weakened version of the viral "vector" was also engineered to reduce any chance that the immune system could attack it.

Knee test

The gene therapy was injected into a small knee muscle in adult mice suffering from an advanced form of Duchenne muscular dystrophy.

Some time later, they were re-tested to see if the physical ability of the muscle to withstand movement without injury had increased.

They found that this - a key measure of the structural strength of the muscle - had improved by 40%.

Professor Jeffrey Chamberlain, from the University of Washington School of Medicine in Seattle, who led the study, said: "We have shown that replacing the dystrophin gene will correct this disease, even in older animals.

"In future research we hope to develop better methods to deliver the gene to all the muscles of the body, as currently we are limited to treating relatively small muscles."

Hurdles ahead

This is not the only obstacle to success in human patients.

Even if scientists could find a way of delivering the drug to muscles all around the body via the bloodstream, there is no guarantee that it could make a difference in the damaged muscle that characterises muscular dystrophy in humans.

Unlike mice, muscle in patients with muscular dystrophy tends to be heavily scarred by repeated injuries suffered while trying to contract it. This may be far more difficult to reverse.

And there are still concerns about both the ability of gene therapy to evade the immune system, and whether an effective dose would prove safe in a human.

However, UK experts said the research was "highly encouraging".

Dr Dominic Wells, a reader in Transgenic Biology in the Gene Targeting Unit at Kings College London, said: "These are incredibly promising results.

"The fact that he has been able to functionally restore this muscle is a very, very key finding.

"He has managed to achieve a very effective gene transfer."

Dr Jenny Versnel, from the Muscular Dystrophy Campaign, said: "When children are diagnosed with Duchenne muscular dystrophy, usually in early childhood, the muscles already display signs of muscle cell breakdown.

"Research to date has tested the applicability of gene therapy using young mice, this new research has shown promising results with inserting a full-length gene into older mice who have greater muscle cell weakness."

The findings were released in the journal Proceedings of the National Academy of Sciences.

[Cyto]

There are three regional differences in brain activity that have not been noted before:

[*]There is a cluster of neurons that changes activity from encoding, to storage, to retrieval, in the basal temporal area, below the temporal lobe.
[*]Neurons that may help people recall something quickly after they have seen it earlier in the day – what scientists call ‘implicit memory’—seem very active in the superior temporal gyrus of the temporal lobe.
[*]There are neurons in the language-dominant hemisphere that respond to more than one modality – memory of both visual and auditory material.

Neurons More Specialized Than Previously Thought
http://www.bio.com/n...e=1&action=view
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“However, we did find that the stem-cell-derived neurons did not make as many synapses as normal neurons,” said Stevens. “It might be that adult stem cells by themselves don’t give rise to cells with sufficient synapses; that we didn’t give them the right environment for synaptic production, or that these particular cultured cells might have contained mutations that reduced synapse production.”

Neural Stem Cells Develop into Functional Neurons
http://www.bio.com/n...e=1&action=view
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Neurons in the brain transmit or fire very fast electrical signals from one region to another. Scientists can measure how cells communicate by measuring the rate of firing (spiking) of neurons. A relatively reliable measure of the work that neurons do, therefore, is reflected by their spiking rates. Neuroscientists have long been interested in finding out what neurons are doing in a local region when given a specific task.

Measuring the Energy Neurons Use
http://www.bio.com/n...e=1&action=view
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Using mice, which offer the closest model to human neurobiology, the scientists found that WNT-3 is only produced by motor neurons in the spinal cord at a crucial stage when sensory neurons come close to them.

Signal That Guides Sensory Neurons
http://www.bio.com/n...e=1&action=view
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Their key observation was that immature stem cells differ from mature neurons in that they express different forms of the Shc adaptor protein—a protein that links growth factor signals to the cellular machinery.

'Shc Switch' and Stem Cell Maturation
http://www.bio.com/n...e=1&action=view

"Here's what happens when you die -- you sit in a box and get eaten by worms. I promise you that when you die, nothing cool happens."

[Cyto]

Using microscale channels cut in an ultrathin biodegradable polymer, a researcher at the U.S. Department of Energy's Ames Laboratory is working to regrow nerve cells. The technique, which may one day allow the paralyzed to walk and the blind to see, has been proven to work for peripheral nerve regeneration in laboratory rats.

Nerve cells are unlike most other biological tissue. When a nerve is severed, the part of the neuron "downstream" of the injury typically dies off. And neurons in the human body can be several feet long. Grafting, which works well for other tissue such as skin, isn't the best option because of loss of nerve function where the donor tissue is removed and the difficulty in getting the nerve cells to line up and reconnect.


Sounds very...Aggravating