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The brain is not dead when the cortex is dead.
#1
I thought this was a topical letter from 2014 which provides some useful information that supports my view that the brain can continue to have some function (albeit not wakeful consciousness), well after 20 seconds of cardiac arrest, up to perhaps a few minutes, and that this period of continued functioning might be extended further by CPR...

I've also quoted from referenced paper [3] further below for readers ease of reference... which shows stark differences in how thalamus neurons respond to oxygen and glucose deprivation, in comparison to deeper brain neurons within the hypothalamus.

[Image: when_is_the_brain_dead.png]

I've copied a bit of the text and a diagram from the third reference in the article for readers ease of reference...

[3] Ischemic vulnerability of the brain decreases rostrocaudally
Magnetic Resonance imaging of patients who survive global ischemia but remain in a persistent vegetative state (PVS), show relatively normal brainstem function but dysfunctional higher brain activity [5] [6] [30] [7], a finding supported by numerous studies measuring regional metabolism [8]. There is also evidence from animal studies that anoxic depolorisation (AD) which is acutely damaging in higher brain [31] is comparatively weak in brainstem. Specifically, AD arising from respiratory arrest in intact rat brain measured using K + -sensitive electrodes [17] showed that the profile of elevated [K + ] o (representing AD strength) is delayed, is slower to rise, and peaks at lower levels in hypothalamus and brainstem compared to cortex and striatum. As well, global ischemia in dogs for 20 minutes [11] evoked a gradient of neuronal injury assessed 7 days later as follows: neocortex, hippocampus, cerebellum > basal ganglia> thalamus > brainstem. In fact, they detected no injury in midbrain, pons or medulla despite all regions being deprived of blood over the same period. The adult hypothalamus and brainstem do not naturally undergo spreading depression [12] so it is not surprising that they are also less supportive of AD.

Neurons in higher brain undergo strong AD (see Introduction) while hypothalamic and brainstem neurons show weak or no AD [15] [16][32]. This also holds for the less metabolically stressed version of AD, spreading depression (ibid) and in slices is obviously independent of regional variation in blood flow. Specifically, using whole-cell patch and 2-photon microscopy, we have previously reported a clear difference in neuronal responses to Oxygen/glucose deprivation between susceptible neocortical pyramidal neurons and more resilient Magnocellular Neuroendocrine Cells in the hypothalamic supraoptic nucleus [15]. Here we examined if and where a demarcation in susceptibility to anoxic depolorisation and spreading depression generation can be identified. We show that the transition from vulnerable to more resilient is at the thalamus-hypothalamus interface. Following 10 minutes of Oxygen/glucose deprivation in rodent slices, the thalamus is essentially dead. No new thalamic neurons can be obtained post-Oxygen/glucose deprivation, even following up to 1 hour recovery in control artificial cerebral spinal fluid. Thalamic neurons, like those of neocortex [33], CA1 hippocampus [34] [35] [36] and striatum [2] undergo strong and irreversible AD that kills the neurons in brain slices.

In contrast, tens of microns away in hypothalamus we recorded three neuronal types in the paraventricular nucleus (PVN) and suprachiasmatic nucleus (SCN) showing comparative resilience to 10 or 15 minutes of Oxygen/glucose deprivation. These neurons recover their membrane potential, input resistance and action potential amplitude. Moreover, newly acquired neurons are readily obtained in the hypothalamus following Oxygen/glucose deprivation, a feat not possible in adjacent thalamus, even following up to an hour of recovery in control artificial cerebral spinal fluid. Their resting membrane potential, input resistance and action potential amplitude are similar to their neuron counterparts not previously exposed to Oxygen/glucose deprivation, further indicating good recovery from Oxygen/glucose deprivation. This resilience is similar to that reported in a fourth hypothalamic region, the supraoptic nucleus [15]. That study sampled only one type of `higher` (neocortical) neuron and one type of `lower` hypothalamic Magnocellular Neuroendocrine neuron but there was no way to generalize that hypothalamic neurons resist ischemic resistance. By sampling 3 additional hypothalamic neuronal types and comparing them to nearby thalamic neurons, this study can make that conclusion.

[Image: when_is_the_brain_dead2.png]
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#2
Hi, Max

The letter you've posted above is based on an incorrect premise and the authors they quoted (Dhanani et al) retracted their statements several months ago. See here :

"The authors conclude that the recording is a false reading and cannot be assumed to indicate that the brain is still functioning."

http://blog.journals.cambridge.org/2017/...ac-arrest/

I posted this on Sleptiko (months ago) in response to a previous post you made on the same subject. Hopefully this will clear the matter up.
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#3
(08-27-2017, 11:24 AM)tim Wrote: Hi, Max

The letter you've posted above is based on an incorrect premise and the authors they quoted (Dhanani et al)  retracted their statements several months ago. See here :

"The authors conclude that the recording is a false reading and cannot be assumed to indicate that the brain is still functioning."

http://blog.journals.cambridge.org/2017/...ac-arrest/

I posted this on Sleptiko (months ago) in response to a previous post you made on the same subject. Hopefully this will clear the matter up.

Yes, the author of the letter disagreed with some of the conclusions of that pilot study. Their reasoning and references are not only interesting, but solid and sound.
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#4
(08-27-2017, 11:35 AM)Max_B Wrote: Yes, the author of the letter disagreed with some of the conclusions of that pilot study. Their reasoning and references are not only interesting, but solid and sound.

We've been through all this before, Max. It can't go anywhere because once the brainstem is knocked out (as in cardiac arrest) the whole caboodle goes down. Even Woerlee admits this. It's just a fact about how the brain works, no blood, no glucose and oxygen, no fuel to power the brain cells (neurons) so everything stops.
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#5
(08-27-2017, 01:19 PM)tim Wrote: We've been through all this before, Max. It can't go anywhere because once the brainstem is knocked out (as in cardiac arrest) the whole caboodle goes down. Even Woerlee admits this. It's just a fact about how the brain works, no blood, no glucose and oxygen, no fuel to power the brain cells (neurons) so everything stops.

Well everything doesn't stop within the brain a few seconds into cardiac arrest, that's the point. The referenced paper [3] above is one of many which show that firing can continue for some time beyond 20 seconds of energy compromise, quite a few minutes actually, depending on the type of cells and their location, and whether or not CPR is started, and it's quality.
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#6
(08-27-2017, 03:00 PM)Max_B Wrote: Well everything doesn't stop within the brain a few seconds into cardiac arrest, that's the point. The referenced paper [3] above is one of many which show that firing can continue for some time beyond 20 seconds of energy compromise, quite a few minutes actually, depending on the type of cells and their location, and whether or not CPR is started, and it's quality.

"Well everything doesn't stop within the brain a few seconds into cardiac arrest, that's the point."

I didn't say it did, Max, I said it stops on average after 20 seconds. The paper above is irrelevant now, the author has admitted that.
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#7
(08-27-2017, 03:14 PM)tim Wrote: "Well everything doesn't stop within the brain a few seconds into cardiac arrest, that's the point."

I didn't say it did, Max, I said it stops on average after 20 seconds. The paper above is irrelevant now, the author has admitted that.

I think your getting muddled up with some other paper... Brisson et. al. 2013 shows activity is possible well beyond 20 seconds, a few minutes at least.
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#8
(08-27-2017, 03:51 PM)Max_B Wrote: I think your getting muddled up with some other paper... Brisson et. al. 2013 shows activity is possible well beyond 20 seconds, a few minutes at least.

Please can you show me the paper ?
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#9
(08-27-2017, 04:03 PM)tim Wrote: Please can you show me the paper ?

A Distinct Boundary between the Higher Brain’s Susceptibility to Ischemia and the Lower Brain’s Resistance

Abstract

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na+/K+ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K+]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.
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#10
(08-27-2017, 04:38 PM)Max_B Wrote: A Distinct Boundary between the Higher Brain’s Susceptibility to Ischemia and the Lower Brain’s Resistance

Abstract

Higher brain regions are more susceptible to global ischemia than the brainstem, but is there a gradual increase in vulnerability in the caudal-rostral direction or is there a discrete boundary? We examined the interface between `higher` thalamus and the hypothalamus the using live brain slices where variation in blood flow is not a factor. Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover. Newly acquired neurons could not be patched following AD, confirming significant regional thalamic injury. Coinciding with AD, light transmittance (LT) imaging during whole-cell recording showed an elevated LT front that initiated in midline thalamus and that propagated into adjacent hypothalamus. However, hypothalamic neurons patched in paraventricular nucleus (PVN, n= 8 magnocellular and 12 parvocellular neurons) and suprachiasmatic nucleus (SCN, n= 18) only slowly depolarized as AD passed through these regions. And with return to control aCSF, hypothalamic neurons repolarized and recovered their input resistance and action potential amplitude. Moreover, newly acquired hypothalamic neurons could be readily patched following exposure to OGD, with resting parameters similar to neurons not previously exposed to OGD. Thalamic susceptibility and hypothalamic resilience were also observed following ouabain exposure which blocks the Na+/K+ pump, evoking depolarization similar to OGD in all neuronal types tested. Finally, brief exposure to elevated [K+]o caused spreading depression (SD, a milder, AD-like event) only in thalamic neurons so SD generation is regionally correlated with strong AD. Therefore the thalamus-hypothalamus interface represents a discrete boundary where neuronal vulnerability to ischemia is high in thalamus (like more rostral neocortex, striatum, hippocampus). In contrast hypothalamic neurons are comparatively resistant, generating weaker and recoverable anoxic depolarization similar to brainstem neurons, possibly the result of a Na/K pump that better functions during ischemia.

Thanks, Max. For a start it doesn't say how they got these readings, or from what creature, alive or just dead and it doesn't say whether the creature is in cardiac arrest or not (does it ? apologies if it does)  

"Whole-cell current clamp recording of 18 thalamic neurons in response to 10 min O2/glucose deprivation (OGD) revealed a rapid anoxic depolarization (AD) from which thalamic neurons do not recover."

That statement is perfectly in line with what I've posted previously. What you're getting at here I think is that these authors think they have found that the neurons in the hypothalamus retain their electrical potential slightly better than the neurons in the thalamus. I'm not a neuroscientist but it wouldn't surprise me as it just means that the hypothalamus is deeper inside and possibly the last bunch of neurons to stop and eventually burst.

It's tiny portion of the brain partly responsible for many important functions. Consciousness is not one of them. If you cut off the blood supply to the brain, the brain stem stops functioning. When doctors are able to determine that the brainstem is badly damaged (in coma) that is all they need to know as regards whether or not there is anything meaningful going on. But coma isn't as severe as cardiac arrest.

I don't see how you can make a case for a tiny area of the brain being responsible for lucid cognition with reasoning and memory formation as occurs in NDE, when the reflexes of the brain that should underpin such experience are just not there (apparently according to medical orthodoxy)
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