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caseload of many Centers was low, because more than 75% of the centers perform less than three aortic arch
[8]
procedures per year .
The ideal cerebral protection during CA is still widely debated. Many reports compare different strategies,
namely DHCA without ACP and MHCA with ACP, but in such a comparison, the increasing surgical
experience can be as important as the surgical strategy . It is possible that techniques now considered less
[9]
appealing can actually yield superior results compared to the past. This can be attributed to improved
knowledge, better materials, and enhanced surgical skills.

In this review, we will briefly describe the energetics of the brain, the mechanisms of neurologic
dysfunctions, and the advantages and disadvantages of the strategies of cerebral protection commonly used
during CA for aortic arch surgery.

ENERGETICS OF THE BRAIN
The brain has a high metabolic demand, accounting for 20% of the total glucose and 20% of the total oxygen
consumed by the human body . ATP, generated primarily by glucose metabolism, is the main energy
[10]
source of the brain. Glucose enters the brain from the blood through the blood-brain barrier (BBB) by
means of glucose transporters. Such capillaries are continuous and non-fenestrated vessels. Their
endothelial cells (ECs), being tightly connected to each other, represent a limitation to paracellular transport
across the endothelium . The walls of capillaries are formed as well by mural cells, which include vascular
[11]
smooth muscle cells, astrocytes and pericytes, which are embedded in the basement membrane and cover
[12]
the blood-brain side of the endothelial wall with their processes [Figure 1]. The membranes of ECs are
then divided into two sides, with different membrane composition [13,14] . As molecules must pass two sheaths
of membrane to enter or leave the brain, the role of the transporters located on each side of the cell
membrane is crucial in controlling this movement. Some substances, such as glutamate, a neurotrasmitter
that can be toxic ay high concentrations, can only be removed from the brain.

Glucose is transported to neurons and astrocytes. However, the presence of astrocytes endfeet that encircle
blood vessels limits the capacity of the neurons to take up glucose directly. It is then possible that most of
the glucose enters the brain through astrocytes [15,16] [Figure 2].

Once glucose enters the neurons, it can undergo the tricarboxylic acid (TCA) cycle in the presence of
oxygen to generate ATP. When it enters the astrocytes, it can be metabolized through the TCA cycle or can
undergo aerobic glycolysis, which is the production of lactate from pyruvate in the presence of oxygen,
[17]
[10]
present in all the brain, even if not uniformly distributed , reaching 25% in specific regions . Aerobic
glycolysis and lactate production are typical of astrocytes and oligodendrocytes but are only marginally
expressed in neurons . Lactate obtained from aerobic glycolysis can be shuttled to neurons, where it is
[15]
subsequently converted into pyruvate again, entering the TCA cycle. This shuttle hypothesis suggests that
neurons use lactate, produced by astrocytes, as an energy substrate. Oligodendrocytes can transport
[18]
lactates , produced by themselves or by astrocytes, to neurons through the myelin, or glucose, if necessary
[Figure 2].

Astrocytes can store glucose as glycogen as well, serving as a metabolic reserve when glucose uptake is
reduced or in stress conditions. Neurons can synthesize glycogen, which is, however, continuously
degraded , as glycogen accumulation in neurons leads to neuronal demise [20,21] . Glycogen is rapidly broken
[19]
down to lactate if neuronal activity is increased or glucose level is low. This mechanism becomes essential to
maintain axon function. Glycogen stores are actively regulated by astrocytes according to glucose levels,
upregulating glycogen stores if glucose level is high and depleting glycogen stores if glucose level is low.