Considering Preservation of Extracellular Space in the Brain

Methods of preserving the brain for the long term immediately following death include cryonics, currently a long-standing but small industry, and plastination, a form of chemical fixation that has not yet progressed to the point of commercial availability for this purpose. Why preserve the brain? Because it is a favorable alternative the the oblivion of the grave, one that offers the possibility of a return to active life in a future in which advanced molecular nanotechnology and cellular medicine can be used to restore a preserved individual. In this age of rapid progress in molecular biochemistry more consideration is being given to proving that ideal preservation techniques do in fact preserve the structures thought to encode memory, as if that is not the case then the whole business is moot. Fortunately memory does appear to be preserved based on evidence to date, but the careful consideration continues:

Although most people usually focus on the brain cells when discussing brain preservation techniques, extracellular space is also worthy of consideration. In vivo, extracellular space makes up around 1/5th of overall brain volume, although this varies based on brain region, developmental stage, and surely many other factors. Over the past few months, researchers published two articles relevant to the preservation and importance of the extracellular space. As a very brief summary, one of the things that the authors show is that extracellular space is dramatically lower (less than 1%) following perfusion fixation than it is following their optimized chemical tissue fixation protocol, which involves varying the osmolarity of the buffer. And among other things, they show that cryofixation of tissue slices better preserves extracellular space as it occurs in vivo in comparison to conventional fixation procedures.

The mechanism for these findings is simple: fixation, as well as the ischemia that typically precedes it, causes a dramatic decrease in the number of extracellular ions, which causes water to enter cells and for them to expand. In particular, it appears that astrocytes expand preferentially during this process. One reason that this matters for people interested in brain preservation is that any information contained within or dependent upon the extracellular space is especially likely to be affected by most extant brain preservation procedures. For example, one extracellular structure proposed to play a role in memory is the perineuronal net. So it's worth asking the question: do perineuronal nets survive fixation? And evidence suggests that they do - indeed, some researchers thought that they were a fixation artifact!

Since water fluctuations are common in vivo, and animals often retain memories following ischemic events that presumably lead to dramatic local osmotic shifts of water, it is likely that most key elements of memory are encoded - or at least, encoded redundantly - by more stable structures than those which would be affected by extracellular water fluctuations. That said, it would be quite worthwhile to consider systematically what structures appear to hold information in the extracellular space, and evaluate whether they are preserved by any brain preservation procedure that purports to retain key elements of personal identity, such as memory.

Link: http://www.brainpreservation.org/the-preservation-of-extracellular-space-in-the-brain/

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