This thesis investigates methods of studying brain energy metabolism with a specific focus on the substrates oxygen and glucose. It details the in vitro development and in vivo characterisation of microelectrochemical sensors for the detection of brain tissue oxygen, and the in vivo characterisation of oxygen and glucose electrodes in the hippocampus utilising the technique of long-term in vivo electrochemistry (LIVE).
Chapter 1 introduces the brain, energy metabolism and neurochemical analysis focusing on oxygen and glucose monitoring in the brain. Chapter 2 discusses the theory relevant to the studies performed in this work, whilst Chapter 3 is a detailed description of sensor construction and techniques used for the in vivo and in vitro characterisation of the sensors utilised in this thesis.
The results are divided into five sections. The first of these, Chapter 4, details the in vitro characterisation of carbon paste electrodes (CPEs) and a Pt-based electrode modified with a membrane, methyl methacrylate (Pt-MMA) and makes comparisons between these two types of electrodes for use in vivo. Following on from the in vitro characterisation chapter, Pt-MMA electrodes were fully characterised in vivo and comparisons were made with previously published CPE data detailed in Chapter 5.
The development and standardisation of a metal-free electrode for use in conjunction with fMRI studies for the detection of brain tissue oxygen is presented in Chapter 6. The complete in vivo characterisation of the fully characterised fMRI compatible O2 electrode developed in the previous chapter is detailed in Chapter 7.
Chapter 8 demonstrates and characterises the simultaneous recording of oxygen and glucose using CPEs and a Pt-based glucose biosensor (Pt/PPD/GOx) in the hippocampus of freely-moving animals, and utilises these sensors to monitor brain energy metabolism in conjunction with a behavioural task. Finally, overall conclusions in relation to the work presented in this thesis are discussed in Chapter 9
