Neuroprotection in hypothermia linked to redistribution of oxygen in brain

Abstract

Hypothermia improves the outcome of acute ischemic stroke, traumatic injury, and inflammation of brain tissue. We tested the hypothesis that hypothermia reduces the energy metabolism of brain tissue to a level that is commensurate with the prevailing blood flow and hence allows adequate distribution of oxygen to the entire tissue. To determine the effect of 32 degrees C hypothermia on brain tissue, we measured the sequential changes of physiological variables by means of PET in pigs. Cerebral blood flow and oxygen consumption (cerebral metabolic rate of oxygen) declined to 50% of the baseline in 3 and 5 h, respectively, thus elevating the oxygen extraction fraction to 140% of the baseline at 3 h. The results are consistent with the claim that cooling of the brain to 32 degrees C couples both energy metabolism and blood flow to a lower rate of work of the entire tissue.

Post Cardiac Arrest Syndrome

“…3,4 The physiological benefits of TH are thought to be multifactorial, including decreases in cerebral oxygen demand and direct cellular effects and a reduction in reactive oxygen species generation. 42 Despite the recommendation that hypothermia should be initiated as soon as possible after cardiac arrest, the method, timing, and duration of hypothermia treatment have yet to be comprehensively studied. Hypothermia can be induced by a variety of different methods, including surface cooling, ice-cold infusions, evaporative transnasal cooling, and endovascular cooling catheters.…”

Post-hypoxic hypothermia is protective in human NT2-N neurons regardless of oxygen concentration during reoxygenation

“…In newborn pigs (papers II and III), therapeutic hypothermia reduced histopathological damage, although statistically significant only in pigs reoxygenated with 100% oxygen and not after reoxygenation with air. It has been suggested that hypothermic neuroprotection is linked to redistribution of oxygen in the brain, as moderate hypothermia in some models reduces cerebral blood flow, decreases metabolic rate and reduces neuronal oxygen uptake 173,[292][293][294] . We did not observe any decrease in striatal microcirculation in the pig model, but found increased striatal oxygen tension in hypothermic compared to normothermic animals.…”

A nitric oxide donor reduces brain injury and enhances recovery of cerebral blood flow after hypoxia-ischemia in the newborn rat

“…To determine whether changes in CBF during HI were linked to cellular metabolism [12,19] independent of NO, we performed HI under conditions of mild hypothermia (Fig. 2).…”