PRIMASENSE

Cerebral energy metabolism underlies the brain's ability to maintain neuronal activity or repair tissue damage. It is important to monitor metabolism in severely brain-injured patients who do not respond to clinical examination, in order to detect possible complications. However, there is no satisfactory method of monitoring metabolism. Brain imaging offers only instantaneous, poorly repeatable measurements, fluorescence microscopy is limited to the tissue surface, and microdialysis induces tissue damage. Chemical microsensors such as those used for glucose monitoring in diabetics are a promising alternative. They are used in rodents to monitor the brain, but no human development has yet been attempted. The aim of this project is to develop implantable chemical microsensors based on enzymatic microelectrodes capable of monitoring interstitial concentrations of oxygen, glucose, lactate, glutamate and glutamine in the brain of non-human primates. This is an essential pre-clinical step towards transferring these devices into the human clinic. These electrodes will need to offer excellent mechanical resistance to pierce the dura mater, as well as excellent stability and selectivity. We will first develop microelectrodes less than 100 µm in diameter, consisting of a carbon fiber inserted into a glass capillary, or carbon/ platinum microelectrodes etched onto a flexible polymer coupled to a rigid guide for in vivo implantation. These electrodes have already been validated in rodents for oxygen detection, and partially in anesthetized primates. Secondly, we will immobilize oxidoreductase enzymes on these microelectrodes with electrochemical mediators offering high stability and selectivity. We will test a Prussian blue polymer electrodeposited on the electrode, as well as four chemical mediators: methylene blue, thionine, toluidine blue and chloro-naphthoquinone. Finally, these devices will be tested in primates, first under terminal anesthesia before scheduled euthanasia, then in awake animals engaged in an attentional task. These new devices will make it possible to monitor brain metabolism in primates on a second-by-second basis and correlate it with cognitive functions that are impossible to study in rodents. We will compare our new oxygen sensors with commercial devices (Sophysa) to demonstrate the advantages of their small size in obtaining more reliable tissue oxygen pressure values that are closer to brain reality. These results will enable clinical applications for metabolic monitoring in brain injured patients following head trauma or subarachnoid haemorrhage. They will enable clinicians to better diagnose neurological complications in these patients, in particular secondary ischemia, to initiate care more rapidly, with greater therapeutic efficacy.