Cerebral metabolic adaptations

Cerebral metabolic adaptation Increased cerebral energy reserve (ATP/ADP) Unclear how this leads to anticonvulsant effect... 

Kennedy, C. Sokoloff, L. (1957). An adaptation of the nitrous oxide method to the study of the cerebral circulation in children normal values for cerebral blood flow and cerebral metabolic rate during childhood. J. Clin. Invest. 36, 1130-7. 

Fig. 4.4. Bar graph of viability thresholds of cerebral blood flow for a variety of functions and metabolites. Note that selective neuronal loss occurs at consistently higher flow values than overt infarction. CMRG, cerebral metabolic rate of glucose PCr, phosphocreatine ATP, adenosine triphosphate. [Adapted and reproduced with permission from Hossmann (1994)]...

Metabolic regulators of cerebral tissue PtO are complex and involve both vascular and metabolic adaptations. For the brain, the pattern of adaptation includes sequential responses that raise brain PtO (Xu and LaManna, 2006). The initial response is to increase blood flow, followed by an increase in hematocrit and then microvessel density as a result of angiogenesis (vascular adaptations) (Brown et al., 1985 Beck and Krieglstein, 1987 LaManna et al., 1992 LaManna and Harik, 1997 Dunn et al., 2000 LaManna et al., 2004)... 

Severe, acute reduetion in oxygenation, for example by complete arrest of uterine flow or complete umbiheal cord occlusion, is not associated with a decrease in eerebrovascular resistance, as is seen in more mild insults. This suggests that the ability of the fetus to adapt to hypoxia has been overwhelmed. The rate at which the fetal arterial O2 content falls may be a determinant of the response elicited whether it be a rapid onset of ECoG isoelectricity (32,120), reduced regional cerebral blood flows (17), a failure of cardiovascular adaptive responses (139), an increase in eerebral lactate production (140), or a 50% reduction in cerebral metabolic rate... 

While currently novel, the idea that cerebral as well as peripheral metabolism can be actively altered during hypoxia-ischemia appears to be well founded. The mechanisms by which reductions in metabolism are achieved are presently unknown but at least two vasoactive compounds important in the hemodynamic response to hypoxia (namely nitric oxide and adenosine) are also able to elicit metabolic alterations and are thus prime candidates for mediation of metabolic adaptations. 

If we may extrapolate from these results to the clinical situation, we conclude that maintenance of optimal intracellular T3 concentrations in the central nervous system requires T4 as a substrate and a series of adaptations in the metabolism of this prohormone and T3, which then compensates for the plasma hypothyroxinemia. To the extent that the compensatory changes described in the cerebral cortex of the hypothyroid rat do not occur in the human, a reduction of serum T4 in iodine deficient persons could present a significant threat to the thyroid status of the cerebral cortex, even if serum T3 remained at normal concentrations. There are no data with respect to the presence of a local T4 to T3 conversion system in the human central nervous system. However, the similarity of the responses of the pituitary-thyroid axis to hypothyroidism and iodine deficiency in the rat and man suggests that the Type 11 deiodinase is common to both species (28,43). Presumably then, the concepts regarding intracerebral thyroid hormone metabolism derived from those experiments in the rat are also relevant to man. 

Figure 4 Development of ovine cerebral oxygen consumption. Brain metabolism increases with gestation, reaching a peak after birth before falling to adult levels. (Adapted from...

Metabolic data from fetal brain studies indicate that moderate hypoxia or asphyxia can be adapted to by increases in cerebral blood flow and/or fractional oxygen extraction (15,111,135-138). Acutely, reductions in cerebral oxygen consumption are small eompared to the reduction in arterial oxygen content (34) however, during severe or prolonged asphyxia, reductions in cerebral oxygen consumption become apparent. 

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