X-Message-Number: 4130
Date: Sun, 2 Apr 1995 00:42:23 -0500 (EST)
From: Bruce Zimov <>
Subject: SCI.CRYONICS: Brain survival
1) On What we are
Declarative and procedural memory, the conscious state, and other brain
functions are preserved in the topology of the neuronal connections, and
the integrity of the cell to maintain its transfer function
2) On When we lose it
THE BRAIN WITHOUT OXYGEN: Causes of Failure and Mechanisms for Survival
by Peter L. Lutz and Goran E. Nilsson c. 1994 ISBN 1-879702-96-7 details
the 8 steps of the Anoxic Brain Catastrophe:
"
1. Halt in oxidative ATP production -> the ATP level falls
2. The ATP utilizing NA+ - K+ pump slows down
3. Net outward leakage of K+ -> progressive depolarization
4. General depolarization. Rapid outflow of K+ and inflow of Ca2+ and Na+
5. Amino acid and Ca2+ transporters driven by the Na+ gradient slow down
or stop
6. Release of excitotoxins such as glutamate, aspartate, and dopamine
7. The excitotoxins activate receptors that cause additional inflow of
Ca2+ and Na+
8. Neuronal death caused by:
a) Activation of lytic processes (proteases, lipases, and
endonucleases) by Ca2+
b) Cell swelling and lysis due to water accompanying the inflow
of ions -> increased cerebral pressure -> permanent ischemia
c) Elevated levels of free fatty acids and other lipids cause
membrane damage
d) Production of cytotoxic free radicals and aldehydes, especially
upon reperfusion"
Interestingly, Lutz and Nilsson give a metric for supplying ATP by
anaerobic glycolysis: "to fully compensate for the loss of oxidative ATP
production, the anoxic brains would have to increase its glycolytic rate
12.5 times" ... "the time to reach the phase 2 threshold can be delayed
by infusing a hyperglycemic saline"
So, no oxygen leads to insufficient ATP production which leads to the Sodium,
etc. flood stretching the ion channels letting water in. Now the cell is
in trouble but the worst is yet to come. Major amounts of
neurotransmitters are released: "A 'domino effect' threatens in this
process, the failed neurons releasing neurotoxic amounts of excitatory
neurotransmitters which stimulate neighboring vulnerable cells to release
their neurotransmitters, which further fatal consequences and a resultant
spreading wave of death."
Lutz and Nilsson have much to say about reperfusion damage: "Possibly
due to impaired uptake mechanisms, glutamate,aspartate, and dopamine may
remain at high concentrations, or rise even further, for several hours
after circulation has been reestablished following ischemia. This may be
an important cause of the delayed anoxic/ischemic brain damage that
occurs after reperfusion of the tissue with oxygenated blood-a somewhat
paradoxical situation called reperfusion damage"
Lutz and Nilsson comment on cell swelling: "The major problem with cell
swelling in the vertebrate brain is probably related to the fact that the
brain is confined in a hard bone envelope. Thus, cell swelling will
result in an increased cerebral pressure, and when this pressure exceeds
the blood pressure, perfusion to the brain will be stopped even if the
original cause of the ischemia or anoxia is eliminated"
These are just snippets but this book is loaded with information. My gut
feeling is that their work will be important for cryonics protocols.
Would opening the skull allow better perfusion of the cryoprotectant, to
compensate for the pressure imbalance due to cell swelling?
The book describes the mechanisms for anoxia survival in other
species. "The crucian carp is so well adapted to anoxia that its anoxia
survival appears to be only limited by a complete depletion of its
glycogen store--the largest found in any vertebrate, those that died
during a 17 day anoxic period had run out of glycogen while survivors
still had glycogen left"
Amazing! The carp lived for more than 17 days without oxygen all due to
glycogen stored in its liver! Anaerobic glycolysis in humans leads to
excess lactate which will cause damage unless flushed away by restored
blood flow. How does the carp deal with this? Lutz and Nilsson have the
answer: "By producing ethanol, the crucian carp avoids the buildup of
high lactate levels and consequent acidosis. Clearly this is a systemic
adaptation that will also facilitate anoxic survival of the brain"
Imagine finding a protocol based on crucian carp biochemistry that would
enable a human brain to be in biochemical stasis long enough to be
transplanted without serious ischemic damage. Chuck the sick body for another
from a donor.
As far as the question of when we lose our topology and transfer
functions, it would appear that if the vesicles contain the weights
required for declarative memory and they burst and take out a whole
region through a "domino effect", then excito-toxins permanently cause
memory loss, and freezing it after the fact won't help. What about the
topology? Well, if procedural memory and consciousness are primarily
related to topology as opposed to the molecular details of the transfer
function, then I think we're ok. You just have to make sure that the
interconnections don't degrade, or break to the point that you cannot put
them back together.
Perhaps this is a way to understand the two approaches to cryonics. The
one approach protects as close to cardiac arrest as possible to
attempt to preserve the transfer functions along with the topology,
the other approach regards the transfer functions as a lost cause
unless you employ some kind of "crucian carp" therapy and so focuses
on preserving the topology only which takes much longer to degrade so
there is no real rush. But, if this characterization is accurate, one
must ask why freeze at all in this last case, since there may be
warm temperature methods of preserving the topology only, e.g.
prehistoric men preserved in a bog resulting in a brain that was
dehydrated but otherwise topologically intact. Why not just dry it out?
Or, what about formaldehyde? The brains in those jars look pretty
whole from a macroscopic perspective, a crude sign of topological
integrity. Einstein preserved his brain in formaldehyde. What he
forgot to tell them was to not cut slices off of it for examination.
3) Digression: On Introspection as an auxiliary method of fact-gathering
Sometimes introspection can give us some clues. For example, if I see a
television image, then close my eyes, and study intently the fading of
the image with my eyes closed, and then voluntarily recall an image of a
friend and then try to notice any fading of the recalled image, I notice
that the fading of the immediate image is very perceptible, but the
fading of the voluntarily recalled image is so rapid as to be
unnoticable. I have found that this is not necessarily the case with
intrusive images that are not voluntarily recalled. On the rare occasion
that these present themselves, there appears to be a definite fading that
is indistinguishable from the immediate fade of direct perception, to the
point that the after image of the recalled image is seen as it fades
without the effort of recall, as if it somehow ended up in layer 6 of the
visual cortex or something.
Bruce Zimov
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