Brains also have supply chain problems: blood flows where it can, and neurons have to make do with what they’re given

Neuroscientists have long assumed that neurons are greedy, hungry units that demand more energy when they become more active, and the circulatory system complies by supplying as much blood as they need to fuel their activity. As neuronal activity increases in response to a task, blood flow to that part of the brain increases even more than energy expenditure, leading to an excess. This elevation is the basis of common functional imaging technology that generates colored maps of brain activity.

Scientists have always interpreted this apparent discrepancy in blood flow and energy demand as evidence that there is no shortage of blood flow to the brain. The idea of ​​an unlimited supply was based on the observation that only about 40% of the oxygen delivered to each part of the brain is used – and this percentage actually drops as parts of the brain become more active. It seemed evolutionarily logical: the brain would have developed this faster-than-necessary increase in blood flow as a safety feature that ensures an adequate oxygen supply at all times.

But does blood distribution in the brain actually support a demand-driven system? Neuroscientist himself, I had previously explored some other assumptions about the most basic facts about brains and found them wrong. To name a few: human brains don’t have 100 billion neuronsalthough they do have the most cortical neurons of any kind; the degree of folding of the cerebral cortex does not indicate how many neurons are present; and it’s not the bigger animals that live longer, but those with more neurons in their cortex.

I believe it is essential to find out what determines blood flow to the brain in order to understand how the brain works in health and disease. It’s like cities have to figure out whether the current power grid will be enough to support future population growth. Brains, like cities, only work when they have enough energy.

Resources such as highways or rivers

But how could I test whether the blood supply to the brain is really demand-driven? My freezers were filled with preserved, dead brains. How do you study energy consumption in a brain that no longer uses energy?

Fortunately, the brain leaves evidence of its energy use through the pattern of the vessels that distribute blood through it. I thought I could look at the density of capillaries – the thin, single-celled vessels that transfer gases, glucose, and metabolites between the brain and blood. These capillary networks would be preserved in the brain in my freezers.

A demand-driven brain should be comparable to a road network. If arteries and veins are the main highways that carry goods to the city from specific parts of the brain, then capillaries are akin to the neighborhood streets that actually deliver goods to their end users: individual neurons and the cells that work with them. Streets and highways are built on demand, and a road map shows what a demand-driven system looks like: Roads are often concentrated in parts of the country where there are more people – the energy-consuming units of society.

A brain with a limited supply, on the other hand, should look like the riverbeds of a country that doesn’t care where people are. Water will flow where it can, and cities just have to adapt and settle for what they can get. Cities are likely to form near major thoroughfares, but without major, purposeful renovations, their growth and activity will be limited by the amount of water available.

Would I notice that capillaries are concentrated in parts of the brain that have more neurons and supposedly require more energy, such as streets and highways built on demand? Or would I find them more like creeks and streams permeating the land where they can, unaware of where most people are, in a supply-driven fashion?

What I found was clear evidence for the latter. For both mice and rats, capillary density makes up a measly 2% to 4% of brain volume, regardless of how many neurons or synapses are present. Blood flows in the brain like water through rivers: where it can, not where it is necessary.

If blood flows regardless of need, it means the brain is actually using blood as it is supplied. We found that the small variations in capillary density in different parts of dead rat brains perfectly matched blood flow and energy expenditure in the same parts of other live rat brains that researchers had measured 15 years earlier.

Resolving blood flow and energy needs

Could the specific density of capillaries in each part of the brain be so limiting that it determines how much energy that part uses? And would that apply to the brain as a whole?

I started working with my colleague Doug Rothman to answer these questions. Together we discovered that not only do the brains of both humans and rats do what they can with the blood they are given and usually operate at about 85% capacity, but that overall brain activity is indeed determined by capillary densitywhile all else being equal.

The reason why only 40% of the oxygen supplied to the brain is actually used is because this is the maximum amount that can be exchanged as the blood rushes past – like workers trying too quickly to retrieve items from a running band. Local arteries can supply more blood to neurons if they start using a little more oxygen, but at the cost of diverting blood away from other parts of the brain. Since the gas exchange was almost at full capacity in the beginning, the oxygen extraction fraction even seems to decrease with a slight increase in the supply.

From a distance, energy use in the brain may look demand-driven, but it’s really supply-constrained.

The blood supply affects brain activity

So why does this matter?

Our findings offer a possible explanation for why the brain can’t really multitask – it just quickly alternates between points of interest. Because blood flow to the entire brain is tightly regulated and remains essentially constant throughout the day as you alternate activities, our research suggests that any part of the brain that experiences an increase in activity – because you start doing math or playing a song, for example for example – can only get a little more blood flow at the cost of redirecting blood flow from other parts of the brain. So the inability to do two things at once may have its origin in the fact that the blood supply to the brain is limited in supply and not based on demand.

Our findings also provide insight into ageing. If neurons have to make do with the energy they can get from a largely constant blood supply, then the parts of the brain with the highest density of neurons will be the first to be affected when there is a shortage – just as the largest cities feel the pain of a drought for smaller ones.

In the cortex, the parts with the highest neuron densities are the hippocampus and the entorhinal cortex. These areas are involved in short-term memory and the suffer from aging first. More research is needed to test whether the parts of the brain most vulnerable to aging and disease are those with the greatest number of packed neurons competing for limited blood supply.

If it is true that capillaries, like neurons, last a lifetime in humans as in laboratory mice, then they may play a greater role in brain health than expected. To keep your brain neurons healthy in old age, it may be a good bet to take care of the capillaries that supply them with blood. The good news is that there are two proven ways to do this: healthy diet And excercisewho are never too late to start.