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Energy reserves and utilization rates in developing brain measured in vivo by 31P and 1H nuclear magnetic resonance
R J Corbett1, A R Laptook, D Garcia
1Ralph Rogers and Mary Nell Magnetic Resonance Center, Department of Radiology, University of Texas Southwestern Medical Center, Dallas 75235-9085.
Insights
Swine brain energy utilization increases with age, with newborns showing higher rates than rodents. Cerebral energy demand decreases during hypoglycemia and prolonged ischemia.
Area of Science:
- Neuroscience
- Biochemistry
- Physiology
Background:
- Cerebral energy metabolism is critical for brain function, especially during development.
- Swine undergo rapid perinatal development, making them a relevant model for studying age-related metabolic changes.
- Understanding cerebral energy utilization is key to comprehending brain vulnerability and resilience.
Purpose of the Study:
- To investigate age-dependent changes in cerebral energy utilization in piglets.
- To quantify the impact of ischemia on brain energy metabolites.
- To compare cerebral energy demands in swine with other species.
Main Methods:
- In vivo 31P and 1H nuclear magnetic resonance spectroscopy (MRS) was used to measure brain metabolites.
- Complete ischemia was induced via cardiac arrest in piglets of different ages (newborn, 10-day-old, 1-month-old).
- Rate constants for metabolite changes and preischemic concentrations were determined to calculate energy utilization flux (approximately P/g/min).
Main Results:
- Cerebral energy utilization increased significantly with age, from 6.5 ± 1.9 μmol approximately P/g/min in newborns to 15.1 ± 3.2 μmol approximately P/g/min in 1-month-old piglets.
- Hypoglycemia decreased cerebral energy utilization rates, while hyperglycemia did not alter them.
- Energy utilization rates declined after the initial minutes of ischemia.
Conclusions:
- Piglet cerebral energy utilization is higher in newborns compared to rodents, consistent with swine's rapid perinatal development.
- Age-related increases in cerebral energy demand are significant during early development.
- Further research is needed to refine estimates of cerebral energy utilization, especially concerning the linearity assumption over time.
Abstract:
Age-related changes in cerebral energy utilization were examined in swine, a species whose maximal rate of development is known to occur in the perinatal period. Interleaved in vivo 31P and 1H nuclear magnetic resonance spectroscopy was used to measure the rates of change in cerebral concentrations of phosphocreatine (PCr), nucleoside triphosphates, and lactate following complete ischemia, induced via cardiac arrest, in a total of 19 newborn, 10-day-old, and 1-month-old piglets. Preischemic concentrations of these three metabolites plus glucose and glycogen were determined in a separate experiment on 12 piglets whose brains were funnel-frozen in situ. The rate constants for the PCr and ATP decline and lactate increase were determined by nonlinear regression fits to the experimental data, assuming first-order kinetics. The rate constants and preischemic metabolite concentrations were used to calculate the initial flux of high-energy phosphate equivalents (approximately P), which was used as an estimate of cerebral energy utilization at the point when ischemia was initiated. Cerebral energy utilization equaled 6.5 +/- 1.9, 9.5 +/- 3.2, and 15.1 +/- 3.2 mumol approximately P/g/min in newborn, 10-day-old, and 1-month-old piglets, respectively. Within each age group the energy utilization rate was not altered by hyperglycemia-induced increases in cerebral energy reserves, but during hypoglycemia cerebral energy utilization rates decrease. The slope of approximately P versus time decreased with the duration of ischemia, indicating that cerebral energy utilization rates decrease after the first few minutes of ischemia. Newborn piglets had higher cerebral energy utilization rates compared with literature values for newborn rats and mice. This is consistent with the concept that newborns from a species with a perinatal stage of maximal growth and development will have higher cerebral energy demands compared with newborns from a species such as rodents, whose maximal growth occurs postnatally. However, this conclusion remains tentative because literature cerebral utilization rates estimated from the initial slope of approximately P-versus-time plots tend to underestimate the true rate, since the assumption of continued linearity may not be valid for the interval chosen.