Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System

Abstract

Summary:This review analyzes, in some depth, results of studies on the effect of lowered temperatures on cerebral energy metabolism in animals under normal conditions and in some selected pathologic situations. In sedated and paralyzed mammals, acute uncomplicated 0.5-to 3-h hypothermia decreases the global cerebral metabolic rate for glucose (CMR glc ) and oxygen (CMRO 2 ) but maintains a slightly better energy level, which indicates that ATP breakdown is reduced more than its synthesis. Intracellular alkalinization stimulates glycolysis and independently enhances energy generation. Lowering of temperature during hypoxia-ischemia slows the rate of glucose, phosphocreatine, and ATP breakdown and lactate and inorganic phosphate formation, and improves recovery of energetic parameters during reperfusion. Mild hypothermia of 12 to 24-h duration after normothermic hypoxic-ischemic insults seems to prevent or ameliorate secondary failures in energy parameters. The authors conclude that lowered head temperatures help to protect and maintain normal CNS function by preserving brain ATP supply and level. Hypothermia may thus prove a promising avenue in the treatment of stroke and trauma and, in particular, of perinatal brain injury.

The Brain is Hypothermic in Patients with Mitochondrial Diseases

“…Hypothermia reduces cerebral glucose and oxygen metabolism, but maintains a slightly better energy level, which indicates that ATP breakdown is reduced more than ATP synthesis. 35 Neurons are among the most metabolically active cells, and most of the ATP generated is used for impulse generation and transmission. An estimated 40% to 50% of the energy goes to maintain membrane potential by driving the membrane sodiumpotassium ATPase pump, 4 while the remaining energy is consumed for synaptic transmission, calcium homeostasis, and other cellular processes including axonal transport.…”

Hypothermic neuroprotection

“…Broadly, it is now well established that cooling sup- presses many of the pathways leading to delayed cell death. As well as reducing cellular metabolic demands, 98,99 hypothermia reduces excessive accumulation of cytotoxins such as glutamate and oxygen free radicals, suppresses the post-ischemic inflammatory reaction and inhibits the intracellular pathways leading to programmed (i.e., apoptosis-like) cell death. Suppression of excitotoxins and free radicals.…”

Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

“…HT after perinatal asphyxia is also recommended by the recent 2010 International Resuscitation Guidelines (International Liaison Committee on Resuscitation) (10). HT suppresses many of the pathways that lead to delayed energy failure and cell death after hypoxia (11,12), including generation of reactive oxygen species (13), excitotoxicity (14), and the inflammatory response (15).Supplemental oxygen was previously recommended for resuscitation of the asphyxiated newborn infant, but after the changes in the 2010 International Liaison Committee on Resuscitation guidelines, it is now recommended that resuscitation of the term infant is best started with air, rather than pure oxygen (10). Evidence from animal studies shows that supplemental oxygen during resuscitation causes significant hyperoxia in the newborn brain (16,17), with increased generation of reactive oxygen species (18), oxidative stress (19), inflammation (20), and cerebral injury (19,21,22).…”