John Krakauer – An Incredible Result

(Photo João Camilo)

An Incredible Result

We published this in 2008  and it got sort of forgotten for a while. But in the last year and a half, it’s just exploded. Many, many papers are coming out on this proportional recovery rule in mouse and man.

And what’s subsequently been found out is that there doesn’t seem to be any positive relationship between the endogenous process going on early in the brain and the compensation-focused therapy being given in parallel. There may even be a negative one: the fact that if you spend that initial short period of endogenous enhanced learning plasticity trying to compensate for the impairment, you’re distracting yourself away from actually recovering the ability.

For example, if I have an impaired right arm after a stroke, and you need to start teaching me how to use my left hand, by the time you start working on the right, the window of opportunity has closed.

Did you experimentally demonstrate the existence of this rule?

No. It was based on an observational longitudinal study I set up at Columbia University along with a colleague (she went on to become a stroke neurologist). We have more recently developed a mouse model of stroke at Johns Hopkins, a project spearheaded by a junior faculty member to gain more insight into the possible mechanisms of spontaneous biological recovery and how it may interact with rehabilitative training.

We took a mouse, gave it a stroke, waited a week before we started training it [perhaps  equivalent to one or three months for humans]. And, as we expected, we didn’t get much improvement because we had waited too long to initiate rehabilitation. In contrast, the mice returned to pre-stroke performance when we started training within 48 hours.

We then decided that if it was true that stroke opens a window of increased responsiveness to training, then paradoxically you could treat the first stroke with a second one. So we took that same mouse, waited a week without training, then gave it another stroke close to the first one, and started training a day later.

And what happened – the final, counter-intuitive, result – was that the mouse got worse and then it returned to normal. We published a paper on this in late 2015.

It’s an incredible result.

It is an incredible result, yes. Actually, when I suggested this experiment to a colleague, to put in an a grant application for the mouse stroke work, he was advised not to by other people in our department, because it sounded so crazy.

Now obviously, it’s going to have to be reproduced, but my guess is that, just like for proportional recovery, some time will pass and then everyone’s going to start trying to see how that experiment worked and go under the hood and really look at the molecular mechanisms.

That means that people who have multiple strokes could have a second chance or a third chance at recovery?

No. Let’s be very clear. Obviously, we did this experiment just to show that stroke can open up a window of increased responsiveness to training. There’s no way we would ever countenance giving human beings another stroke. Nonetheless, it strongly suggests that there really is a window of opportunity for recovery and that the right therapies to exploit it should be devised.

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