Dr. Jerry Silver, Talk #2

Note: Matt Roderick is going to introduce the late morning speakers.  He has a son in a chair; first came to w2w in Phoenix 2 years ago.  He’s been a loud and persistent voice in Minnesota, where he lives, on behalf of the cure.

About Jerry Silver . . . he did a little for us in MN about 6 weeks ago.  He came to speak at the UM stem cell institute, where we’re trying to get a bill passed.  While he was there he talked with a researcher who I’ve been lobbying to get a chronic model going . . . she told me after listening to him that she’s on board for it now.

Here’s Jerry.

This is going to be about bridging a complete transection model — at first about an acute model and then at the end about the work they’ve done toward getting a chronic model going.

What we know about why axons don’t generate . .   The lesion.  Bleeding.  Macrophages rush in.  Axons die back.  Astrocytes move away and surround the entire area of inflammation with a scar, which keeps the inflammation from spreading.  Inside the core of the lesion are bunches of oligodendrocytes, but they’re not myelinating.

We decided to either build a bridge through this or just bypass the whole damn thing.  How do you get axons to cross?  You can create a conditioning response, give them some high test fuel . . . and get rid of the inhibitory molecules, like with chondroitinase (ChABC).  High test fuel and no guard rails.  Zoom!

In the 1800s they knew that central nervous system (CNS) nerve cells could be bridged across multiple centimeters to peripheral nerves.  BUT once they got to the end of the bridge, they couldn’t get out.  Why not?  25 years of research, and we learn that there’s a little scar filled with proteoglycans, which seemed to be like a little cul-de-sac for axons.  We solved that.  We published that last year, which is how I got invited to be here.

Now we’ve gone further.  The lesions we worked on were hemisections, and we wanted to try to do a bridge for a complete transection, the hardest bridge to build.  (He’s very enthusiastically giving credit to Yu Shang Lee, who is a bladder expert and a brilliant surgeon, along with one of his own cohorts in Ohio, Marc DePaul.)

They tried to use their strategies to all ow paralyzed animals (and hopefully humans) to urinate normally after complete transection SCI . . . can this be done?

In 1996, Chang published a paper claiming that with peripheral nerve grafting (PNG) and FGF, they could restore some walking to animal models.  Word got out that this was not good research because it couldn’t be reproduced.  Jerry says he asked Yu Shang Lee (who knew Chang) if the animals could really walk . . . answer was NO . . . but they sure could pee.

So interesting!  So Jerry’s lab did an experiment with PNG and FGF and ChABC (chondroitinase) . . . the FGF is crucial.  In their acute model, they labeled the nerve fibers, looking for the path of the axons relative to the spot in the brain where urination is controlled.

Showing a movie of these propriospinal neurons having crossed the cavity and keeping on going, 7 millimeters past the other side.  You can see hundreds of them, passing the gap, and going all the way to the lumbar sacral levels, the terminal point.

Okay, so some neurons can grow?  We just heard that this can’t happen the other day . . . so who are these special guys who can grow?  It takes them six months to get all the way from the brain stem down, but they can do it.  We haven’t even knocked out pten.  These are the primitive brain stem neurons that control urination, not the ones that control voluntary movement.

Showing graphs of rat peeing behavior.  They pee like crazy, all night long, dozens of times, over and over.  After injury, their bladders stay full all the time . .  they only pee five or six times.   If they get the treatment, they gradually start peeing more normally over a six-month period.  This is highly quantified, dense data that shows the rats have become physiologically normal.

So . . . is it regeneration or plasticity?  They transect and find that it’s regeneration.  They confirm that result with pharmacology, by blocking functions with drugs and watching the behaviors change. Proven beyond a shadow of a doubt that regeneration is critical for return of function in the bladder.


All brand new data . . . we started with a contusion injury.  Bridged with the triple combo, nerve graft, FGF, and ChABC.  And wait.  And wait.  And wait.

Oh, no . . . the animals got worse, far worse.  Depressing.

New strategy.  So they added an intermediate phase, in which those sleepy axons got waked up.  They went in and added FGF and Fibrin and ChABC, and wait, and then did the graft.  And that time it worked!

I just got to see the anatomy before I got on a plane to come here . . . there are thousands of axons in the graft and many of them are exiting.  At least at two months, we know that we can get regeneration.

Now we have a strategy.  We have to remove the scar surgically, but there may be other ways.  We can do any creative attempt to alter the wound.  We can add peptides, we can alter pten, we can add neurotrophins, we can do anything we can think of, and we hope a lot of people will get excited about this and JOIN US.

You’re hearing it from me, Jerry Silver, working2walk 2012:

After complete cord transection even at chronic stages long-distance regeneration is possible.

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One Comment on “Dr. Jerry Silver, Talk #2”

  1. […]  Ah, so many things from the 2nd Dr. Jerry Silver talk.  One is the moderator, Matt Roderick, telling us that Dr. Silver convinced a researcher Matt […]

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