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Some human tissue can survive without oxygen a couple of minutes, even hours.

Why are the neurons are so "weak" and depends so much on oxygen and other nutrients and cannot live without them for more than a few seconds or 1 or 2 minutes?

Are they missing some parts of their cells which can store nutrients for worse times in favor of their function or what is the case?

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Maybe because as soon as the hardware stops, the "software" is no more? (half-joking answer) –  Tobia Mar 17 '13 at 15:09
This has been addressed on quora:… –  dd3 Mar 18 '13 at 0:40
So, it is not the lack of stored stuff(oxygen, nutrients) in neurons? Does that mean that they could in fact survive if they want to, but actually the way how they respond to the lack of oxygen makes them die so quicky? So, ste structure/organelas in them could in fact support them for a longer time, but the "dead" signals they are receiving (chemically) turn them off and they die? –  Derfder Mar 18 '13 at 10:02
Well, it's not really a "dead" signal - excitation is part of normal neuronal activity. Excitotoxicity is when there is too much excitation and it kills the neuron: –  dd3 Mar 18 '13 at 16:47

3 Answers 3

up vote 4 down vote accepted

Neurons use lot of energy to maintain their polarized state, this is not required to other cells [1,2].

When O2 or blood flow (which is carrying the nutrients) is reduced, the neuronal ATP levels breaks down very fast, with 90% ATP depleted in less than 5 minutes. Without ATP, the neuron can not maintain the correct ion flux, so depolarization occurs causing glutamate excitotoxicity, cell swelling and finally cell death.



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There are many factors contributing to neurons dying much faster than other cell types.

This website does not provide original references (for this question, it does for the rest of the article) but sounds trustworthy:

Some factors extracted from here are:

  • Aside from small amounts in astrocytes, there is no glycogen storage in the brain.
  • Fatty acids cannot cross the blood-brain barrier.
  • Lack of a backup energy sources such as creatine phosphate in muscle cells.

Which leave the brain crucially dependent on oxydative phosphorylation, i.e. glucose and oxygen. Additionally of course, neurons are metabolically highly active and use up the small amounts of stored nutrients available at a faster rate than most cells. This is because they need to maintain strong ion gradients across their entire membrane, which spans a larger area than most other cell types due to extensive axonic and dendritic trees; not to mention constantly exocytosing neurotransmitters from the axon's numerous terminals.

Coupled with excitotoxicity as the actual mechanism inducing cell death as explained in the Quora answer linked above (, this seems to be a sufficient explanation.

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The short answer is: neurons do NOT always die quickly when deprived of nutrients. The longer answer is the following:

I am a professional researcher in brain ischemia (ischemia = no blood flow), which is the topic of the question. Armatus' answer was correct insofar as neurons have very limited energy reserves and therefore loose ATP very quickly. Gianpaolo R gave the correct time course for ATP loss. However, Gianpaolo R's explanation of cell death applies only if the ischemia lasts for about 20-30 minutes. In this case, the cells swell and lyse by a process called necrosis.

However, if the duration without blood flow (which is the duration with no oxygen and nutrients) is less than 20 - 30 minutes, then the cells do not die by necrosis. It is less well-known to lay people, but well-known to neurologists that the neurons will die days or weeks after the ischemia in a process called "delayed neuronal death".

What is also less known to lay people is that if the duration of ischemia is less than about 7 minutes (this depends on the species, e.g. human, rat mouse, etc), no neurons die, and in fact, they are protected for a short while from a similar insult. This is a phenomenon known as "ischemic preconditioning".

The explanation of necrosis is uncontroversial. However, no one knows what causes delayed neuronal death or preconditioning responses. The excitotoxicity mentioned by Armatus is a popular theory in the field, that has been largely discredited for a variety of reasons I will not go into here. It is also popular to believe the delayed neuronal death is due to a process called apoptosis, but this also has fallen out of favor in recent years.

Hence, right now, there are many competing ideas as to why the neurons die in a delayed fashion, and the simple fact is, no one knows for sure why they die in this way.

As you may imagine, being a worker in this field, I have a theory that I think is the most feasible of all. But it is a mathematical theory that applies to any injured cell, not just neurons deprived of blood flow. The theory is very simple conceptually. It says that when a cell is injured it gets damaged (call it D), but also activates genetic responses to protect itself (call this S). If the genetic protective responses are greater than the damage, that is, if S > D, then the cell recovers and lives. If the damage is greater than the stress responses (D > S), the cell dies. The rate at which the cell recovers or dies is inversely proportional to |D - S| after D and S have run their course interacting with each other.

This last statement precisely answers your questions. Neurons will die quickly when |D-S| is a large number. They will die slowly when |D-S| is a small number.

Now, this is just a qualitative description. The theory actually consists of mathematical equations that predict many things. You will note it is a true theory and does not rely on the biological specifics of the system under study. I am currently measuring the theory in my lab. I am confident it will be a very useful theory not only for explaining brain ischemia, but many other forms of cell injury.

The original article detailing this theory can be obtained at this link.

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