Cerebral Oxygen Delivery and Consumption in Brain-Injured Patients

Abstract

Organism survival depends on oxygen delivery and utilization to maintain the balance of energy and toxic oxidants production. This regulation is crucial to the brain, especially after acute injuries. Secondary insults after brain damage may include impaired cerebral metabolism, ischemia, intracranial hypertension and oxygen concentration disturbances such as hypoxia or hyperoxia. Recent data highlight the important role of clinical protocols in improving oxygen delivery and resulting in lower mortality in brain-injured patients. Clinical protocols guide the rules for oxygen supplementation based on physiological processes such as elevation of oxygen supply (by mean arterial pressure (MAP) and intracranial pressure (ICP) modulation, cerebral vasoreactivity, oxygen capacity) and reduction of oxygen demand (by pharmacological sedation and coma or hypothermia). The aim of this review is to discuss oxygen metabolism in the brain under different conditions.

Keywords: TBI; brain; consumption; delivery; oxygen.

Figure 1

“Mitochondrial respiration” benefits when reducing nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH₂) components are created by the tricarboxylic acid (TCA) cycle. In the inner mitochondrial membrane, electrons generated from NADH and FADH2 are oxidized to NAD+ and FAD+ by complexes I and II. Afterward, these electrons are transferred successively to complex III, cytochrome c and complex IV. Cytochrome c oxidase (COX, complex IV) transmits electrons to molecular oxygen. This is an important enzyme in the mitochondrial electron transport chain (ETC) connecting oxygen with oxidative phosphorylation [37]. The transmission of electrons through the ETC is connected with proton transfer from the mitochondrial matrix, across the inner membrane to the intermitochondrial membrane space. This translocation develops an electrochemical gradient of protons (pH gradient and membrane potential). These molecules may drift through the F1Fo-ATP synthase (complex V) or back to the mitochondrial matrix [38]. Importantly, complex V connect protons transfer to the production of ATP from adenosine diphosphate (ADP) and phosphate. Under normal oxygen levels, pyruvate, as a product of glycolysis, is transported into the mitochondria, and is transformed into acetyl-CoA by the pyruvate dehydrogenase (PDH) complex [39]. Afterward, acetyl-CoA connects with oxaloacetate and creates citrate—the first step in the tricarboxylic acid cycle. Reducing equivalents in this cycle impacts ETC to production of ATP and reactive oxygen species (ROS) for signaling, and the intermediates of TCA are used for biosynthetic processes such as lipid synthesis [40].

Figure 2

Hyperthermia is associated with poor neurological outcomes because it predisposes to greater secondary damage. Temperature changes lead to elevation of cytokine release, higher neutrophil activity and elevated metabolic expenditure. Hyperthermia also increases ROS generation and apoptosis.