Comment by burning_hamster | Hacker News Reader

Comment by burning_hamster | Hacker News Reader

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burning_hamster

This is correct. For obvious reasons, selection pressures on terminal physiological processes are non-existent (or at least very small). Also, the press release makes it sound as this "wave of death" is something these people discovered or even characterized. It is a well known phenomenon that anybody doing any sort invasive brain imaging observes at some point. As they state in the abstract of the paper:

> While the molecular signature of anoxic depolarization (AD) is well documented, ...

The molecular mechanism is also pretty straightforward: dying cells rupture and release ATP. ATP is not only the ultimate energy source but also a potent messenger molecule. In the brain, it excites other neurons, resulting in activation and hence depolarisation of other neurons. Furthermore, in large concentrations, it also induces apoptosis in nearby cells (not just neurons). The result is a chain reaction were the death of some neurons induces death in other neurons, and so on, and this "wave of death" is preceded by a faster moving wave of electrical activation.

Would it be possible to preemptively inject any substance that neutralized these effects directly in the neocortex in patients to give one last chance of treating them before cerebral death or the damage of the initial rupture of neurons is already too great to allow a person to make a recovery?

Due to the blood-brain barrier, it is quite difficult to get substances injected into the blood into the brain (though some obviously do, otherwise there would be no psychoactive substances). Injecting into brain tissue directly is possible but probably not useful in an emergency: if you want to inject into cortex directly, you have to inject at ulta-low (yet positive) pressures (otherwise you destroy a lot of tissue just by injecting), and diffusion from the site of injection would be slow. In other words, you would have to drill a thousand holes into someones skull, and inject tiny volumes over the course of minutes each time. You could inject into the ventricles. That can be done quicker and with larger volumes without incurring too much damage, but again, lymphatic flow is very slow, so getting the drug into the tissue would take a long time (hours). So from first principles, you are fighting an uphill battle, and the incline is very steep.

The findings in the paper are interesting in the latter scenario, as they identify the deep cortical layers as the likely drivers of the wave of death (not a surprising finding for various reasons so quite likely true). Deep cortical layers are closer to the ventricles, so access would be a bit better than to the cortex in general.

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