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Ventilation and Brain Metabolism

Bo K. Siesjö, Martin Ingvar

10.1002/cphy.cp030205

Source: Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing

Originally published: 1986

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Brain Metabolism: A Brief Overview
1.1 Metabolic Rate and Blood Flow
1.2 Neurotransmitters and Cerebral Metabolic Rate
1.3 Cellular Function: Dependence on ATP and Oxygen
2 Influence of Hypoxia on Brain Metabolism
3 Carbon Dioxide and Brain Energy Metabolism
3.1 Hypocapnia
3.2 Hypercapnia
3.3 Regulation of Intracellular pH
3.4 Regulation of Cerebral Blood Flow
3.5 Neurotransmitters
4 Possible Coupling Mediators in Brain
4.1 Barbiturate Anesthesia: A Hypometabolic State
4.2 Epileptic Seizures: A Hypermetabolic State
4.3 Cerebral Metabolism and Physiological Control Mechanisms
Figure 1. Figure 1.

Correlation between local cerebral blood flow and local glucose utilization in unanesthetized rat. Points, mean blood flow obtained withiodoantipyrine technique of Sakurada et al. 181 and mean glucose utilization obtained with [14C]deoxyglucose technique of Sokoloff et al. 198 in numerous brain structures.

Adapted from Sokoloff 197
Figure 2. Figure 2.

Relationship between arterial partial pressure of O2 (arterial ) and cerebrovenous (superior sagittal sinus) in artificially ventilated rats during progressive reduction in inspired O2 concentration.

From MacMillan and Siesjö 127
Figure 3. Figure 3.

Brain tissue concentrations of lactate, phosphocreatine (PCr), ATP, ADP, and AMP during progressive lowering of arterial . At each level of hypoxia, was held constant for 15–30 min before tissue was analyzed. Filled circles, animals in which mean arterial blood pressure was maintained at 120 mmHg or higher. Open circles, animals in which pressure fell to 80–100 mmHg.

From Siesjö et al. 191
Figure 4. Figure 4.

Changes in pyruvate and citric acid cycle intermediates in rat cerebral cortex after 1‐, 2‐, 15‐, and 30‐min exposure to hypoxic gas mixture. Oxygen content of insufflated gas mixture was lowered to yield arterial of ∼25 mmHg. Values are means ±SE in percent of control. Filled symbols, values significantly different from control (P < 0.05). Pyr, pyruvate; Citr, citrate; Iso‐Citr, isocitrate; α‐Kg, α‐ketoglutarate; Succ, succinate; Fum, fumarate; mal, malate; OAA, oxaloacetate.

From Norberg and Siesjö 150
Figure 5. Figure 5.

Hydroxylation of tyrosine and tryptophan in rat brain in vivo as function of inspired O2 concentration (and arterial O2 saturation). Hydroxylation was measured as amount of dihydroxyphenylalanine (DOPA) and 5‐hydroxytryptophan (5‐HTP) accumulated after inhibition of aromatic amino acid decarboxylase.

From Davis and Carlsson 46
Figure 6. Figure 6.

Cerebral blood flow as function of arterial partial pressure of CO2 () in rats.

From Sage et al. 179
Figure 7. Figure 7.

Influence of arterial hypocapnia on calculated intracellular pH and on cerebral cortical concentrations of lactate and pyruvate in anesthetized rat. Intracellular pH was calculated on assumption of 10% or 20% extracellular fluid volume. Curves joining open circles in upper panels denote expected pH changes in system in which pH is not influenced by acid production. Tissue CO2 tensions derived from corresponding arterial values. ECS, extracellular space.

From MacMillan and Siesjö 128
Figure 8. Figure 8.

Influence of arterial on lactate/pyruvate ratio, phosphocreatine (PCr) and creatine concentrations, and adenylate energy charge (ATP + 0.5 ADP/ATP + ADP + AMP) of rat cerebral cortex.

From Siesjö 186
Figure 9. Figure 9.

Influence of hypercapnia (administration of 5% or 45% CO2 to ventilated rats) on cerebral cortical concentrations of pyruvate and citric acid cycle intermediates. Values are means ± SE in percent of control. Filled symbols, values significantly different from control (P < 0.05). See Fig. 4 for abbreviations.

From Folbergrová et al. 65
Figure 10. Figure 10.

Cerebral cortical concentrations of glutamate, glutamine, and aspartate during exposure of ventilated rats to ∼10% CO2. Values are means ± SE. Filled circles, values significantly different from control (P < 0.05).

From Folbergrová et al. 65
Figure 11. Figure 11.

Influence of hypercapnia and hypocapnia on rate of tyrosine and tryptophan hydroxylation (cf. Fig. 5). Open circles, changes during hypocapnia (low venous ) and hypercapnia (high venous ) in normoxic animals. Filled circles, hypercapnic animals made moderately hypoxic to normalize venous ; tryptophan hydroxylation but not tyrosine hydroxylation is normalized.

From Carlsson et al. 29
Figure 12. Figure 12.

Cerebral blood flow (CBF) and adenylate energy charge as functions of cerebal metabolic rate for O2 () in ventilated rats. 1) hypothermia, 22°C; 2) barbiturate, 150 mg/kg; 3) N2O/O2, analgesia; 4) hyperthermia, 41.5°‐42°C; 5) immobilization stress; 6) bicuculline‐induced seizures.

Adapted from Nilsson et al. 144 and Siesjö 186


Figure 1.

Correlation between local cerebral blood flow and local glucose utilization in unanesthetized rat. Points, mean blood flow obtained withiodoantipyrine technique of Sakurada et al. 181 and mean glucose utilization obtained with [14C]deoxyglucose technique of Sokoloff et al. 198 in numerous brain structures.

Adapted from Sokoloff 197


Figure 2.

Relationship between arterial partial pressure of O2 (arterial ) and cerebrovenous (superior sagittal sinus) in artificially ventilated rats during progressive reduction in inspired O2 concentration.

From MacMillan and Siesjö 127


Figure 3.

Brain tissue concentrations of lactate, phosphocreatine (PCr), ATP, ADP, and AMP during progressive lowering of arterial . At each level of hypoxia, was held constant for 15–30 min before tissue was analyzed. Filled circles, animals in which mean arterial blood pressure was maintained at 120 mmHg or higher. Open circles, animals in which pressure fell to 80–100 mmHg.

From Siesjö et al. 191


Figure 4.

Changes in pyruvate and citric acid cycle intermediates in rat cerebral cortex after 1‐, 2‐, 15‐, and 30‐min exposure to hypoxic gas mixture. Oxygen content of insufflated gas mixture was lowered to yield arterial of ∼25 mmHg. Values are means ±SE in percent of control. Filled symbols, values significantly different from control (P < 0.05). Pyr, pyruvate; Citr, citrate; Iso‐Citr, isocitrate; α‐Kg, α‐ketoglutarate; Succ, succinate; Fum, fumarate; mal, malate; OAA, oxaloacetate.

From Norberg and Siesjö 150


Figure 5.

Hydroxylation of tyrosine and tryptophan in rat brain in vivo as function of inspired O2 concentration (and arterial O2 saturation). Hydroxylation was measured as amount of dihydroxyphenylalanine (DOPA) and 5‐hydroxytryptophan (5‐HTP) accumulated after inhibition of aromatic amino acid decarboxylase.

From Davis and Carlsson 46


Figure 6.

Cerebral blood flow as function of arterial partial pressure of CO2 () in rats.

From Sage et al. 179


Figure 7.

Influence of arterial hypocapnia on calculated intracellular pH and on cerebral cortical concentrations of lactate and pyruvate in anesthetized rat. Intracellular pH was calculated on assumption of 10% or 20% extracellular fluid volume. Curves joining open circles in upper panels denote expected pH changes in system in which pH is not influenced by acid production. Tissue CO2 tensions derived from corresponding arterial values. ECS, extracellular space.

From MacMillan and Siesjö 128


Figure 8.

Influence of arterial on lactate/pyruvate ratio, phosphocreatine (PCr) and creatine concentrations, and adenylate energy charge (ATP + 0.5 ADP/ATP + ADP + AMP) of rat cerebral cortex.

From Siesjö 186


Figure 9.

Influence of hypercapnia (administration of 5% or 45% CO2 to ventilated rats) on cerebral cortical concentrations of pyruvate and citric acid cycle intermediates. Values are means ± SE in percent of control. Filled symbols, values significantly different from control (P < 0.05). See Fig. 4 for abbreviations.

From Folbergrová et al. 65


Figure 10.

Cerebral cortical concentrations of glutamate, glutamine, and aspartate during exposure of ventilated rats to ∼10% CO2. Values are means ± SE. Filled circles, values significantly different from control (P < 0.05).

From Folbergrová et al. 65


Figure 11.

Influence of hypercapnia and hypocapnia on rate of tyrosine and tryptophan hydroxylation (cf. Fig. 5). Open circles, changes during hypocapnia (low venous ) and hypercapnia (high venous ) in normoxic animals. Filled circles, hypercapnic animals made moderately hypoxic to normalize venous ; tryptophan hydroxylation but not tyrosine hydroxylation is normalized.

From Carlsson et al. 29


Figure 12.

Cerebral blood flow (CBF) and adenylate energy charge as functions of cerebal metabolic rate for O2 () in ventilated rats. 1) hypothermia, 22°C; 2) barbiturate, 150 mg/kg; 3) N2O/O2, analgesia; 4) hyperthermia, 41.5°‐42°C; 5) immobilization stress; 6) bicuculline‐induced seizures.

Adapted from Nilsson et al. 144 and Siesjö 186
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Article Title: Ventilation and Brain Metabolism
 

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Bo K. Siesjö, Martin Ingvar. Ventilation and Brain Metabolism. Compr Physiol 2011, Supplement 11: Handbook of Physiology, The Respiratory System, Control of Breathing: 141-161. First published in print 1986. doi: 10.1002/cphy.cp030205