A fully implantable telemetry system for the chronic monitoring of brain tissue oxygen in freely moving rats

The ability to monitor tissue oxygen concentration in a specific region of the brain in a freely moving animal could provide a new paradigm in neuroscience research. We have developed a fully implantable telemetry system for the continuous and chronic recording of brain tissue oxygen (PO(2,BR)) in conscious animals. A telemetry system with a sampling rate of 2kHz was combined with a miniaturized potentiostat to amperiometrically detect oxygen concentration with carbon paste electrodes. Wireless power was employed to recharge the telemeter battery transcutaneously for potential lifetime monitoring. Rats were implanted with the telemeter in the peritoneal cavity and electrodes stereotaxically implanted into the brain (striatum or medulla oblongata). While the animals were living in their home cages the sensitivity to changes in oxygen was validated by repeatedly altering the inspired oxygen (10%, 100%, respectively) or a pharmacological stimulus (carbonic anhydrase inhibitor: acetazolamide 50mg/kg IP). Basal level of PO(2,BR) was monitored for 3weeks and showed good overall stability and good correlation to movement such as grooming. During hypoxia, PO(2,BR) decreased significantly by -51%±2% from baseline, whereas it increased by 34%±3% during hyperoxia. Following the systemic administration of acetazolamide, PO(2,BR) increased by 38%±4%. We propose this new technology provides a robust method to measure changes in oxygen concentration in specific areas of the brain, in conscious freely moving rats. The ability to track long term changes with disease progression or drug treatment may be enabled.

[1]  M. Fillenz,et al.  Characterization of carbon paste electrodes in vitro for simultaneous amperometric measurement of changes in oxygen and ascorbic acid concentrations in vivo. , 1996, The Analyst.

[2]  R. Wightman,et al.  Evoked Neuronal Activity Accompanied by Transmitter Release Increases Oxygen Concentration in Rat Striatum in vivo but Not in vitro , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[3]  Aiguo Patrick Hu,et al.  Novel technology for the provision of power to implantable physiological devices. , 2007, Journal of applied physiology.

[4]  M. Raichle Behind the scenes of functional brain imaging: a historical and physiological perspective. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Jeff F Dunn,et al.  Modeling of the response of ptO2 in rat brain to changes in physiological parameters. , 2005, Advances in experimental medicine and biology.

[6]  Martyn G Boutelle,et al.  Measurement of brain tissue oxygen at a carbon paste electrode can serve as an index of increases in regional cerebral blood flow , 1997, Journal of Neuroscience Methods.

[7]  Charles Nicholson,et al.  Diffusion and Ion Shifts in the Brain Extracellular Microenvironment and Their Relevance for Voltammetric Measurements , 1995 .

[8]  John P. Lowry,et al.  Brain Tissue Oxygen: In Vivo Monitoring with Carbon Paste Electrodes , 2005, Sensors (Basel, Switzerland).

[9]  M. D. Rooij,et al.  Electrochemical Methods: Fundamentals and Applications , 2003 .

[10]  Y. Hoshi Functional near-infrared spectroscopy: potential and limitations in neuroimaging studies. , 2005, International review of neurobiology.

[11]  M. Fillenz,et al.  Evidence for uncoupling of oxygen and glucose utilization during neuronal activation in rat striatum. , 1997, The Journal of physiology.

[12]  Studies of a glassy carbon electrode for brain polarography with observations on the effect of carbonic anhydrase inhibition. , 1965, The Alabama journal of medical sciences.

[13]  Kazuto Masamoto,et al.  Apparent diffusion time of oxygen from blood to tissue in rat cerebral cortex: implication for tissue oxygen dynamics during brain functions. , 2007, Journal of applied physiology.

[14]  G L Shulman,et al.  INAUGURAL ARTICLE by a Recently Elected Academy Member:A default mode of brain function , 2001 .

[15]  J. Paton,et al.  Elevated vertebrobasilar artery resistance in neonatal spontaneously hypertensive rats. , 2011, Journal of applied physiology.

[16]  D. Heistad,et al.  Characteristics of reactive hyperemia in the cerebral circulation. , 1984, The American journal of physiology.

[17]  Fiachra B. Bolger,et al.  An in vitro characterisation comparing carbon paste and Pt microelectrodes for real-time detection of brain tissue oxygen. , 2011, The Analyst.

[18]  I A Silver,et al.  Tissue oxygen tension and brain sensitivity to hypoxia. , 2001, Respiration physiology.

[19]  Fiachra B. Bolger,et al.  Characterisation of carbon paste electrodes for real-time amperometric monitoring of brain tissue oxygen , 2011, Journal of Neuroscience Methods.

[20]  G. Lembo,et al.  'Alzheimer-like' pathology in a murine model of arterial hypertension. , 2011, Biochemical Society transactions.

[21]  L. C. Clark,et al.  Chronically implanted polarographic electrodes. , 1958, Journal of applied physiology.

[22]  John P. Lowry,et al.  Real-time electrochemical monitoring of brain tissue oxygen: A surrogate for functional magnetic resonance imaging in rodents , 2010, NeuroImage.

[23]  Giammario Calia,et al.  Real-time monitoring of brain tissue oxygen using a miniaturized biotelemetric device implanted in freely moving rats. , 2009, Analytical chemistry.

[24]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[25]  N. Lassen,et al.  Cerebral blood flow and end-tidal PCO2 during prolonged acetazolamide treatment in humans. , 1990, The American journal of physiology.