Does body mass and size influence the time before irreversible brain damage?

Elisa Araldi
PhD student
New York University School of Medicine

Howard, Great Britain

Does body mass and size influence the time before irreversible brain damage?

Elisa Araldi
HHMI predoctoral fellow,
PhD student,
Sackler School of Biomedical Sciences,
New York University School of Medicine
The size of an average human brain is 1,349 g (2.98 lb). Although genetics is the main factor responsible for brain size, the difference between populations with the biggest brain and the smallest is only 120 grams. Furthermore, the difference in brain size between males and females (i.e., sexual dimorphism) is about 150 grams. Brain mass is about 2% of the average human body mass, but its metabolic needs are very high. In fact, the brain consumes about 20% of the total oxygen supply and glucose and uses them almost exclusively through aerobic glycolysis, providing a very fast and efficient source of energy.

The 100 billion neurons that populate our brain are the avid consumers of oxygen and glucose. The neurons are the cells that create our thoughts and emotions; store memories; and generate any other brain function such as speech, movement, and control of vital functions. Even though neurons are 10- to 50-fold less abundant than glial cells—the cells that support and protect neurons—they use most of the brain metabolic energy to generate the electrical signals to perform their functions.

Unfortunately, despite its high oxygen and glucose demand, the brain is not capable of storing metabolic products; therefore, it is very susceptible to ischemia. Even though the brain has stem cells, neurons cannot regenerate like other cells (such as epithelial cells in the skin or intestine or hepatocytes in the liver). Furthermore, because neurons are very special cells that store information and so specialized that each subset is responsible for a cognitive or motor function, once they are lost, their function is also lost. Fortunately, the brain has great plasticity and if only a subset of neurons dies (during a stroke, for example), neurons in other parts of the brain can replace the lost functions—however, they can’t replace the lost memories.

Blood circulation is responsible for bringing oxygen and glucose to every cell of the body and to remove waste metabolites. Although atmospheric oxygen pressure is about 21%, or 160 mmHg, partial oxygen pressure in the tissues is about 5%, or 40 mmHg. Cells use very precise regulatory mechanisms to sense nutrients and oxygen and to keep them at equilibrium. For instance, oxygen sensing is regulated by hypoxia-inducible factors that are responsible for the de novo angiogenesis in tissues, as well as for switching to anaerobic metabolism, which allows the cell to produce energy with less oxygen consumption. This is a very efficient mechanism that permits the survival of cells at moderate hypoxia levels (about 1% oxygen pressure in the tissue). Hypoxia also triggers an adaptation to survival in cells that should not survive. For example, tumors often grow faster than their blood supply and undergo hypoxia, which helps them create new vessels to increase their supply of nutrients.

No matter how big or small, tall or short, a person is, every cell in the body has an almost constant supply of nutrients and oxygen thanks to uniform distribution of capillaries. Because the brain is such an expensive organ in terms of metabolic consumption, not only for humans but also for other mammals, the amount of capillary length and blood flow per cortical neuron is conserved across mammals. When the heart stops, the cells in the body are deprived of oxygenated blood. Because of the brain's high metabolic demand, loss of blood supply can result in irreversible brain damage in as little as 3 minutes, and neurons are the most affected cells.

The uniform distribution of capillaries and the ubiquitous availability of oxygen are the factors that explain why the time it takes to produce irreversible brain damage is the same in every human being. In fact, studies on patients that have been hospitalized with stroke show that body mass index does not predict the amount of damage that ischemia produces, even though it significantly affects the time of recovery because of metabolic, circulatory, and inflammatory complications in bigger patients. Note that although obesity does not affect the amount of damage caused by ischemia, it has been associated with increased stroke and myocardial infarction risk because of the proinflammatory, prothrombotic state of the patient. However, an unsuspected factor does accelerate or slow down the process. It has been shown that atmospheric temperature greatly affects the time it takes to produce irreversible brain damage. For example, as the temperature decreases, metabolic activity slows down and oxygen consumption is reduced; therefore, neurons die more slowly.