I'll eventually organize my thoughts in something worthy of a post. Until then, this has already gone into way more detail than I intended. Thus, briefly:

The damage that is occurring - distortion of membranes, denaturation of proteins (very likely), disruption of signalling pathways. Just changing the exact localization of Ca microdomains within a synapse can wreak havoc, replacing the liquid completely? Not going to work.

I don't necessarily think that low temps have anything to do with denaturation. Replacing the solvent, however, would do it almost unavoidably (adding the cryoprotectant might not, but removing it during rehydration will). With membrane-bound proteins you also have the issue of asymmetry. Proteins will seem fine in a symmetric membrane, but more and more data shows that many don't really work properly; there is a reason why cells keep phosphatydilserine and PIPs predominantly on the inner leaflet.