Jerry Silver and Other Discussion from ChinaSCINet Update

[paolocipolla]

Learn from yesterday, live for today, hope for tomorrow. The important thing is not to stop questioning.
Albert Einstein


I agree, do others?

Soon after my SCI my understanding of SCI research was very poor, so I had relatively few questions, but as my understanding of it gets better the number of questions I have keep growing and I have seen the same happen to others.
Questions are essential in any learning process, but also for agitating the field to make faster progress happen etc..

So I agree with Albert based on my personal experience

Paolo

[jhope]

In our lab we have been experimenting on strategies to bridge a chronic spinal cord contusive injury cavity. We have found that it is absolutely essential to physically remove the tough scar membrane that surrounds the wound cavity. If we don't remove scar then there is no regeneration and all the stem cells in the world will not by themselves break this down. The scar is present and it needs to be dealt with.

Merry Xmas

It will be 20 years at least at that stage to a treatment. Notice no motor or sensory function.

happy new years except for us......

[paolocipolla]

[QUOTE=Wise Young;1631505]

I do agree with you that tough fibrous "scar" tissues form around cuts of the spinal cord where the dura was not repaired and fibroblasts from outside the spinal cord have invaded into the injury site and astrocytes have proliferated to wall them off.
What would you do in that case? Leave the fibrous scar there and just inject UCB cells?

It is interesting that many laboratories have reported regeneration of axons across cut spinal cord injury sites without removing any "scar" tissue from the injury site. The Liu, et al. 2011 paper [2], reporting that PTEN deletion allows massive corticospinal tract regeneration, without anything being done to remove or prevent scar formation, seems to contradict the notion that a physical scar prevents axonal growth.
..but that was acute SCI..

Wise.

[paolocipolla]

I was talking about animal studies. In terms of animal models, our laboratory developed and did the most studies of spinal cord contusion. I organized a group called the multicenter animal spinal cord injury study (MASCIS), consisting of eight leading spinal cord injury centers in the United States, funded by NIH. In one study, we studied 500 rats that had been injured with a 10 gram weight dropped 12.5 mm, 25.0 mm, and 50.0 mm onto the thoracic spinal cord.

The 12.5 mm weight drop produces "incomplete" spinal cord injury from which 90% of rats will recover locomotion. The 25.0 and 50.0 mm weight drops produce severe and complete spinal cord injuries from which 90% and 100% of the rats do not recover weight-supporting locomotion. This is the largest study of contused spinal cords ever done.

We did not see glial scars surrounding the injury site of the kind that Jerry described. In fact, a majority of the animals do not have a cavity at the contusion site. Instead, they have a loose matrix of glial cells at the contusion site, through which many axons passed. The more severe injuries tended to have more cavities but most of the spinal cords did not have cavities.

Wise.

Wise,

I am very interested in understanding better the MASCIS study.

How long after the injury were the animals sacrfied?
How much BBB score did the rats that got 25mm weight drop recover?
How much the rats that got 50mm weight drop?

Paolo

[Wise Young]

Wise,

I am very interested in understanding better the MASCIS study.

How long after the injury were the animals sacrfied?
How much BBB score did the rats that got 25mm weight drop recover?
How much the rats that got 50mm weight drop?

Paolo

I attach a reprint of the paper. If I remember correctly, most of the rats were euthanized at 6 weeks after injury. The BBB scores of the rats with 25 mm weight drop injuries averaged about 8 (non-walking). We studied 3 contusion levels, i.e. the 12.5, 25.0, 50.0 mm, about 150-200 rats per group.

Wise.

[paolocipolla]

So when it comes to the scar thing, what does everyone think about Hans' research of basically reprogramming the tissue at the site? It sounds kind of sci-fi like, but it may be an idea like this that works. In cases like Wise is talking about where there is no cavity maybe this could be very promising?

It's an interesting approach and in case it works it can be very usefull if not essential to repair the spinal cord.
The idea is not new, but perhaps it is now duable as Hans explained.
Few years ago I have discussed this approach with a young german neuroscientist.. He was presenting a poster of how he generated astrocites from neural stem cell. I asked him what about reversing the process in the case of the SCI glial scar? He was intrigued by the question and he speculated that it could have been possible in the future to do that.

Paolo

[Solan]

Solan,

could you check with the spinal unit in Oslo to see if/when they are planning to start clinical trials with UCB cells?

Paolo

I just spoke to Oslo for you and they said that you should plan your own trial Paulo and start harassing yourself instead.

[Wise Young]

I do agree with you that tough fibrous "scar" tissues form around cuts of the spinal cord where the dura was not repaired and fibroblasts from outside the spinal cord have invaded into the injury site and astrocytes have proliferated to wall them off.
What would you do in that case? Leave the fibrous scar there and just inject UCB cells?

It is interesting that many laboratories have reported regeneration of axons across cut spinal cord injury sites without removing any "scar" tissue from the injury site. The Liu, et al. 2011 paper [2], reporting that PTEN deletion allows massive corticospinal tract regeneration, without anything being done to remove or prevent scar formation, seems to contradict the notion that a physical scar prevents axonal growth.
..but that was acute SCI..

Wise.

Paolo,

Penetrating wounds of the spinal cord are relatively rare. For example, we did not see any case of a penetrating or transecting wound of the spinal cord in 41 ASIA A patients that we transplanted cells into so far, 28 of which are chronic and 13 were subacute. All the spinal cord appear intact from the outside. We inject the cells into the spinal cord surrounding the injury site, into the dorsal root entry zones above and below the injury site.

Yes, Liu, et al. 2010 did assess regeneration in "acute" spinal cord injury, in the sense that the rats already had PTEN deleted before they were injured. On the other hand, the regeneration across the injury site took a long time. Kai Liu had to wait 6-8 weeks before he saw the axons grow across the injury site. In rat and mouse time, each week is equal to about a month. If a glial scar formed, it should have been there within 2-3 weeks.

It seems to me that the burden of proof should lie on those people claiming that there is a "scar" that obstructs axonal growth rather than on people who don't see any scar there and are finding axons that grow into the contusion site. If a scar is there and is truly blocking axonal growth in contused spinal cords, why are we seeing so many axons crossing the injury site in the chronically injured spinal cord?

Wise.

[Moe]

I know a man who was injured at c5 that regained almost all function after nearly 18 years after injury. 12 years after his injury his hands and remaining arm muscles woke up out of nowhere, 3-4 years after that was his legs. Nowadays he barely uses a cane. He works with my mom as a maintenance guy and never met anyone else as hyperactive...

He keeps my hopes up, having this 'scar' didn't seem to block anything for him, fortunately and lucky for him his 'fibers' found its way to reconnect on their own.

His advice to me was "never tell you mind that it's over, keep positive thoughts along with a positive attitude"

To me I'm convinced with research there will be a way the fibers will reconnect regardless if this 'scar' is there or not.

Let’s keep our hopes up and may the year 2013 give us good research results.

[Chaz19]

very interesting. Have they done MRIs on him before and after to determine how he regained his function.