Title : In vivo characterisation of microamperometric sensors in the brain extracellular fluid of immunocompromised mice
Abstract:
This presentation details the in vivo characterisation of microamperometric sensors for the real-time monitoring of nitric oxide (NO), oxygen (O2) and hydrogen peroxide (H2O2) in the brain extracellular fluid of immunocompromised NOD SCID mice. Highly selective and sensitive NO, O2 and H2O2 sensors were implanted into NOD SCID mice having been previously characterised in vitro and in freely moving rats. The performance of the sensors was confirmed by systemic administration of characterisation compounds to the animal which lead to perturbation of the respective amperometric currents. In summary, control saline administrations caused transient changes in amperometric current for all sensors that were not significantly different than baseline levels. Systemic administration of the nitric oxide synthase inhibitor, L-NAME, and the pre-cursor for NO synthesis, L-arginine, caused a significant decrease and increase respectively, in NO current. Similarly, administration of L-NAME, the carbonic anhydrase inhibitor, Diamox, and the non-volatile anaesthetic, chloral hydrate, resulted in a significant decrease and increase respectively in O2 current. Furthermore, the H2O2 biosensor responded to increasing concentrations in vivo following local administrations of exogenous H2O2 and anti-oxidant inhibitors. In vivo interference investigations, performed using systemic administrations of sodium ascorbate indicated only slight deviations in H2O2 current over a two-hour period. The latter indicates the ability of the H2O2 sensor to retain its selectivity once implanted. In addition, 24-hour recordings were investigated for all sensors to identify any diurnal variations in the recorded current. It was concluded that diurnal variations were present in the recorded signal of all three sensor types. Moreover, the stability of the sensors was examined to allow for long term recordings. The stability of the current recorded of each of the sensors was observed to remain stable for a period of at least 5 days. These findings corroborate the reliability of the amperometric sensors to perform continuous, long-term recordings in NOD SCID mice.
Audience take away:
- How to characterise a microamperometric sensor in the in vivo environment.
- How to measure neurochemical events in real-time by perturbation of the brain microenvironment
- The use of amperometry for its application in the study of brain disorders.
- The identification of diurnal and nocturnal variations in the rodent brain
- The ability to record neurochemical events over a number of days due to the stability of the amperometric sensors.
Awareness of work being undertaken by the SysMedPD Consortium into developing a neuroprotective compound in the treatment of PD.
