Biotelemetric Monitoring of Brain Neurochemistry in Conscious Rats Using Microsensors and Biosensors

In this study we present the real-time monitoring of three key brain neurochemical species in conscious rats using implantable amperometric electrodes interfaced to a biotelemetric device. The new system, derived from a previous design, was coupled with carbon-based microsensors and a platinum-based biosensor for the detection of ascorbic acid (AA), O2 and glucose in the striatum of untethered, freely-moving rats. The miniaturized device consisted of a single-supply sensor driver, a current-to-voltage converter, a microcontroller and a miniaturized data transmitter. The redox currents were digitized to digital values by means of an analog-to-digital converter integrated in a peripheral interface controller (PIC), and sent to a personal computer by means of a miniaturized AM transmitter. The electronics were calibrated and tested in vitro under different experimental conditions and exhibited high stability, low power consumption and good linear response in the nanoampere current range. The in-vivo results confirmed previously published observations on striatal AA, oxygen and glucose dynamics recorded in tethered rats. This approach, based on simple and inexpensive components, could be used as a rapid and reliable model for studying the effects of different drugs on brain neurochemical systems.

[1]  Pierre J Magistretti,et al.  Brain lactate kinetics: Modeling evidence for neuronal lactate uptake upon activation. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[2]  J. Lowry,et al.  Novel integrated microdialysis-amperometric system for in vitro detection of dopamine secreted from PC12 cells: design, construction, and validation. , 2008, Analytical biochemistry.

[3]  Robert D. O'Neill,et al.  Development of a distributed, fully automated, bidirectional telemetry system for amperometric microsensor and biosensor applications , 2007 .

[4]  R. O'Neill,et al.  Effect of Probe Size on the Concentration of Brain Extracellular Uric Acid Monitored with Carbon Paste Electrodes , 1994, Journal of neurochemistry.

[5]  Toni Bayans.  Handbook of Laboratory Animal Management and Welfare, 2nd ed. , 2000 .

[6]  A. Turner,et al.  Glucose oxidase: an ideal enzyme , 1992 .

[7]  Dean C. Jeutter,et al.  Overview of Biomedical Telemetry Techniques , 1983, Engineering in Medicine and Biology Magazine.

[8]  R G Shulman,et al.  Energy on Demand , 1999, Science.

[9]  M. Fillenz.  The role of lactate in brain metabolism , 2005, Neurochemistry International.

[10]  Robert D. O'Neill,et al.  Design and construction of a low cost single-supply embedded telemetry system for amperometric biosensor applications , 2007 .

[11]  R. Nussbaum,et al.  Ascorbic-acid transporter Slc23a1 is essential for vitamin C transport into the brain and for perinatal survival , 2002, Nature Medicine.

[12]  J. Lowry,et al.  Behaviourally induced changes in extracellular levels of brain glutamate monitored at 1 s resolution with an implanted biosensor , 1998 .

[13]  M. Fillenz,et al.  Real-time monitoring of brain energy metabolism in vivo using microelectrochemical sensors: the effects of anesthesia. , 2001, Bioelectrochemistry.

[14]  Chikara Abe,et al.  Long-term hypergravity induces plastic alterations in vestibulo-cardiovascular reflex in conscious rats , 2007, Neuroscience Letters.

[15]  M. Fillenz,et al.  In vivo determination of extracellular brain ascorbate , 1996, Journal of Neuroscience Methods.

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

[17]  Run-jing Zhou,et al.  [The present status and development of biotelemetry]. , 2002, Zhongguo yi liao qi xie za zhi = Chinese journal of medical instrumentation.

[18]  M. Fillenz,et al.  The role of astrocytes and noradrenaline in neuronal glucose metabolism. , 1999, Acta physiologica Scandinavica.

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

[20]  B. Långström,et al.  Tracing oxygen metabolism by use of positron emitter oxygen-15. , 1997, Biochemical and biophysical research communications.

[21]  Colin L. Masters,et al.  Neurodegenerative diseases and oxidative stress , 2004, Nature Reviews Drug Discovery.

[22]  J. Rawlins,et al.  Voltammetrically monitored brain ascorbate as an index of excitatory amino acid release in the unrestrained rat , 1984, Neuroscience Letters.

[23]  Frieder W. Scheller,et al.  Electrochemical sensors: enzyme electrodes and field effect transistors , 1996 .

[24]  S. Wolfensohn,et al.  Handbook of Laboratory Animal Management and Welfare , 1994 .

[25]  J. Lowry,et al.  Characterization in vitro and in vivo of the oxygen dependence of an enzyme/polymer biosensor for monitoring brain glucose , 2002, Journal of Neuroscience Methods.

[26]  J. Lowry,et al.  Biosensor for neurotransmitter L-glutamic acid designed for efficient use of L-glutamate oxidase and effective rejection of interference. , 1997, The Analyst.

[27]  Lisa R Leon,et al.  Biotelemetry transmitter implantation in rodents: impact on growth and circadian rhythms. , 2004, American journal of physiology. Regulatory, integrative and comparative physiology.

[28]  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.

[29]  J. Andersen,et al.  Oxidative stress in neurodegeneration: cause or consequence? , 2004, Nature Reviews Neuroscience.

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

[31]  P. Enrico,et al.  On the mechanism of d‐amphetamine‐induced changes in glutamate, ascorbic acid and uric acid release in the striatum of freely moving rats , 2000, British journal of pharmacology.

[32]  Huangxian Ju,et al.  Amperometric glucose sensor based on catalytic reduction of dissolved oxygen at soluble carbon nanofiber. , 2007, Biosensors & bioelectronics.

[33]  H. S. Wolff,et al.  iRun: Horizontal and Vertical Shape of a Region-Based Graph Compression , 2022, Sensors.

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

[35]  Martyn G Boutelle,et al.  An amperometric glucose-oxidase/poly(o-phenylenediamine) biosensor for monitoring brain extracellular glucose: in vivo characterisation in the striatum of freely-moving rats , 1998, Journal of Neuroscience Methods.

[36]  M. Rice.  Ascorbate regulation and its neuroprotective role in the brain , 2000, Trends in Neurosciences.

[37]  Pier Andrea Serra,et al.  Development of a Parallel-Computing Embedded Telemetry System for Voltammetric Microsensor and Biosensor Applications , 2009 .

[38]  M. Hediger.  New view at C , 2002, Nature Medicine.

[39]  G. Monaco,et al.  The Neurotoxin 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Induces Apoptosis in Mouse Nigrostriatal Glia , 2002, The Journal of Biological Chemistry.