Disentangling astroglial physiology with a realistic cell model in silico

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we systematically incorporate multi-scale, tri-dimensional astroglial architecture into a realistic multi-compartmental cell model, which we constrain by empirical tests and integrate into the NEURON computational biophysical environment. This approach is implemented as a flexible astrocyte-model builder ASTRO. As a proof-of-concept, we explore an in silico astrocyte to evaluate basic cell physiology features inaccessible experimentally. Our simulations suggest that currents generated by glutamate transporters or K+ channels have negligible distant effects on membrane voltage and that individual astrocytes can successfully handle extracellular K+ hotspots. We show how intracellular Ca2+ buffers affect Ca2+ waves and why the classical Ca2+ sparks-and-puffs mechanism is theoretically compatible with common readouts of astroglial Ca2+ imaging

Observer-Based State Feedback for Enhanced Insulin Control of Type ‘I’ Diabetic Patients

During the past few decades, biomedical modeling techniques have been applied to improve performance of a wide variety of medical systems that require monitoring and control. Diabetes is one of the most important medical problems. This paper focuses on designing a state feedback controller with observer to improve the performance of the insulin control for type ‘I’ diabetic patients. The dynamic model of glucose levels in diabetic patients is a nonlinear model. The system is a typical fourth-order single-input-single-output state space model. Using a linear time invariant controller based on an operating condition is a common method to simplify control design. On the other hand, adaptive control can potentially improve system performance. But it increases control complexity and may create further stability issues. This paper investigates patient models and presents a simplified control scheme using observer-based feedback controllers. By comparing different control schemes, it shows that a properly designed state feedback controller with observer can eliminate the adaptation strategy that the Proportional-Integral-Derivative (PID) controllers need to improve the control performance. Control strategies are simulated and their performance is evaluated in MATLAB and Simulink

A therapy parameter-based model for predicting blood glucose concentrations in patients with type 1 diabetes

In this paper, the problem of predicting blood glucose concentrations (BG) for the treatment of patients with type 1 diabetes, is addressed. Predicting BG is of very high importance as most treatments, which consist in exogenous insulin injections, rely on the availability of BG predictions. Many models that can be used for predicting BG are available in the literature. However, it is widely admitted that it is almost impossible to perfectly model blood glucose dynamics while still being able to identify model parameters using only blood glucose measurements. The main contribution of this work is to propose a simple and identiable linear dynamical model, which is based on the static prediction model of standard therapy. It is shown that the model parameters are intrinsically correlated with physician-set therapy parameters and that the reduction of the number of model parameters to identify leads to inferior data fits but to equivalent or slightly improved prediction capabilities compared to state-of-the-art models: a sign of an appropriate model structure and superior reliability. The validation of the proposed dynamic model is performed using data from the UVa simulator and real clinical data, and potential uses of the proposed model for state estimation and BG control are discussed