Interpretation of NMR spectroscopy human brain data with a multi-compartment computational model of cerebral metabolism

Abstract

One of the main difficulties in studying human brain metabolism at rest and during neuronal stimulation is that direct quantitative information of metabolite and intermediate concentrations in real time from in vivo and in situ brain cells is extremely difficult to obtain. We present a new six compartment dynamic computational model of the astrocyte-glutamatergic neuron cellular complex, previously used and validated for steady state investigations [1],which utilizes Michaelis-Menten type kinetic expressions for the reaction fluxes and transport rates. The model is employed to interpret experimental data (total tissue concentrations of glucose, lactate, aspartate, and glutamate) collected via NMR spectroscopy [2] in terms of compartmentalized metabolism. By integrating numerical methods with Bayesian statistics, we obtain an ensemble of models in statistical agreement with the data. Moreover, our preliminary results seem to suggest that NMR spectroscopy detects the time profile of the concentrations of glucose, lactate and aspartate in glutamatergic neuron. © 2011 Springer Science+Business Media, LLC.