Abstract
We describe a computational model to simulate measurements from near-infrared spectroscopy (NIRS) and magnetic resonance spectroscopy (MRS) in the piglet brain. Piglets are often subjected to anoxic, hypoxic and ischaemic insults, as experimental models for human neonates. The model aims to help interpret measurements and increase understanding of physiological processes occurring during such insults. It is an extension of a previous model of circulation and mitochondrial metabolism. This was developed to predict NIRS measurements in the brains of healthy adults i.e. concentration changes of oxyhaemoglobin and deoxyhaemoglobin and redox state changes of cytochrome c oxidase (CCO). We altered and enhanced the model to apply to the anaesthetized piglet brain. It now includes metabolites measured by 31P-MRS, namely phosphocreatine, inorganic phosphate and adenosine triphosphate (ATP). It also includes simple descriptions of glycolysis, lactate dynamics and the tricarboxylic acid (TCA) cycle. The model is described, and its simulations compared with existing measurements from piglets during anoxia. The NIRS and MRS measurements are predicted well, although this requires a reduction in blood pressure autoregulation. Predictions of the cerebral metabolic rate of oxygen consumption (CMRO2) and lactate concentration, which were not measured, are given. Finally, the model is used to investigate hypotheses regarding changes in CCO redox state during anoxia.
Highlights
In preclinical neonatology research, piglets are often used as experimental models for human neonates
The results showed a decrease in DHbO2 and increase in DHHb during anoxia
After anoxia there was an increase in total haemoglobin concentration indicating an increase in cerebral blood volume
Summary
Piglets are often used as experimental models for human neonates. At birth, their brains have a similar level of maturity to that of human brains [1]. Many studies have used piglets to help understand the effects of oxygen deprivation on cerebral blood flow and metabolism [2,3]. Piglets have been used to investigate encephalopathy following hypoxia–ischaemia (HI), a major cause of perinatal brain injury [4]. One review found 23 per cent of 292 animal studies of perinatal hypoxic ischaemic encephalopathy had used piglets [5]. We have adopted a systems biology approach, and developed
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