The dynamic availability and strictly regulated delivery of primary energy substrates, predominantly glucose and, secondarily, ketone bodies, across the blood-brain barrier to sustain the extraordinarily high metabolic demands of neuronal and glial cells. A consistent and balanced fuel supply is absolutely essential for maintaining optimal cognitive function, ensuring mood stability, and preventing central fatigue. Disruptions in this supply can rapidly lead to significant neurological and cognitive impairment.
Origin
This concept is derived from neurophysiology and metabolic biochemistry, which established the brain’s unique and non-negotiable reliance on specific energy sources for continuous function. The term ‘Fuel Supply’ highlights the continuous and critical logistics of energy transport and utilization in the central nervous system. Clinical research in this area focuses on conditions like hypoglycemia, cerebral ischemia, and metabolic encephalopathy.
Mechanism
Glucose is transported into the brain via specialized GLUT transporters, where it is metabolized through glycolysis and oxidative phosphorylation to generate the vast majority of the required ATP. Under conditions of fasting or a ketogenic state, the liver produces ketone bodies, which are shuttled across the blood-brain barrier and serve as an alternative, highly efficient fuel source for neurons. Hormones like insulin and glucocorticoids indirectly regulate this supply by controlling systemic glucose homeostasis and influencing the expression of brain energy transporters.
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