Department of Chemistry

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Adrian Michael

Professor

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901 CHVRN
Chevron Science Center, 219 Parkman Avenue

Pittsburgh, PA 15260
412-624-8560

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Research Overview

Electrochemistry/Bioanalytical Chemistry

Monitoring chemical processes in living animals is a challenging analytical task. This is especially true in the central nervous system, where information is carried between neurons by very low levels of very short-lived substances, called neurotransmitters. Monitoring neurotransmitters in living animals has been so difficult that most neurochemical studies are performed on dissected brain tissue, which makes it difficult to know what the results tell us about the living brain. The development of new analytical tools will enable a better understanding of the central nervous system and, in turn, facilitate improvements in human neurological health. This lab is focussed on the development of minute analytical devices, either sensors or sampling devices, that can be used to monitor selected neurochemicals in brain extracellular fluid. Much of our work uses electroanalytical techniques in conjunction with microelectrodes, which have dimensions of just a few micrometers. These tiny electrodes are well suited to brain research because they cause very little damage to the delicate tissue. Some of our electrodes are even smaller than the cells of the brain. Please visit our group homepage to view some pictures of our electrodes taken with an electron microscope.

With these microelectrodes we are able to monitor the neurotransmitters called catecholamines. Catecholamines are important in movement control, stress, drug abuse, and Parkinson's disease. By immobilizing enzymes onto the electrode, we can develop microsensors for the enzyme substrate. Recently, we have demonstrated that this strategy can be used to monitor choline in brain tissue and we are now working towards a microsensor for acetylcholine, the transmitter that seems to go wrong in Alzheimer's disease.

While the microelectrodes have many advantages, many compounds important in brain function, such as peptides and proteins, are not amenable to electrochemical techniques. So, we are also devising techniques for collecting and analyzing nanoliter-sized samples of extracellular fluid. The goal here is to construct devices just as small as the microelectrodes in order to keep tissue damage at the smallest possible level. In vivo experiments with these devices are just now getting underway.

Publications

“Dexamethasone-Enhanced Continuous Online Microdialysis for Neuromonitoring of O2 after Brain Injury,” Robbins EM, Jaquins-Gerstl AS, Okonkwo DO, Boutelle MG, Michael AC* ACS Chem. Neurosci. 2023, 14, 2476-2486
“Validation of Dexamethasone-Enhanced Continuous-Online Microdialysis for Monitoring Glucose for 10 Days after Brain Injury,” Gifford EK, Robbins EM, Jaquins-Gerstl A, Rerick MT, Nwashuku EL, Weber SG, Boutelle MG, Okonkwo DO, Puccio AM, Michael AC* ACS Chem. Neurosci. 2021, 12, 3588-3597
“Miniaturized probe on polymer SU-8 with array of individually addressable microelectrodes for electrochemical analysis in neural and other biological tissues,” Marchoubeh ML, Cobb SJ, Tello MA, Hu M, Jaquins-Gerstl A, Robbins EM, Macpherson JV, Michael AC, Fritsch I Anal Bioanal Chem 2021, 413, 6777-6791
“Dexamethasone-Enhanced Microdialysis and Penetration Injury,” Jaquins-Gerstl A*, Michael AC Front. Bioeng. Biotechnol. 2020, 8, 602266
“Real-Time Fast Scan Cyclic Voltammetry Detection and Quantification of Exogenously Administered Melatonin in Mice Brain,” Castagnola E, Robbins EM, Woeppel KM, McGuier M, Golabchi A, Taylor IM, Michael AC, Cui XT* Front. Bioeng. Biotechnol. 2020, 8, 602216
“Regional variation in striatal dopamine spillover and release plasticity,” Walters SH, Shu Z, Michael AC, Levitan ES ACS Chem. Neurosci. 2020, 11, 888-899
“ Real-time monitoring by dexamethasone-enhanced microdialysis in the injured rat cortex,” Robbins EM, Jaquins-Gerstl A, Fine DF, Leong CL, Dixon CE, Wagner AK, Boutelle MG, and Michael AC ACS Chem. Neurosci. 2019, 10, 3521-3531
“Enhancing continuous online microdialysis using dexamethasone: measurement of dynamic neurometabolic changes during spreading depolarization,” Varner EL, Leong CL, Jaquins-Gerstl A, Nesbitt KM, Boutelle MG, and Michael AC ACS Chem. Neurosci. 2017, 8, 1779-1788
“Dexamethasone retrodialysis attenuates microglial response to implanted probes in vivo,” Kozai TDY, Jaquins-Gerstl A, Vazquez AL, Michael AC, and Cui XT Biomaterials 2016, 87, 157-169
“Enhanced intracranial microdialysis by reduction of traumatic penetration injury at the probe track,” Varner EL, Jaquins-Gerstl A, and Michael AC ACS Chem. Neurosci 2016, 7, 728-736
“In Vivo Monitoring of Serotonin in the Striatum of Freely Moving Rats with One Minute Temporal Resolution by Online Microdialysis-Capillary High-Performance Liquid Chromatography at Elevated Temperature and Pressure,” Zhang J, Jaquins-Gerstl A, Nesbitt KM, Rutan SC, Michael AC, and Weber SG Anal. Chem 2013, 85, 9889-9897
“The kinetic diversity of striatal dopamine: evidence from a novel protocol for voltammetry,” Walters SH, Robbins EM, and Michael AC  ACS Chem. Neurosci. 2016, 7, 662-667
“Pharmacological mitigation of tissue damage during brain microdialysis,” Nesbitt KM, Jaquins-Gerstl A, Skoda E, Wipf P, Michael AC Anal. Chem 2013, 85, 8173-8179
“The dopamine patchwork of the rat nucleus accumbens core,” Shu Z, Taylor IM, Michael AC Eur. J. Neurosci 2013, 38, 3221-3229
“Restricted diffusion of dopamine in the rat dorsal striatum,” Taylor IM, Illitchev A, Michael AC ACS Chem. Neurosci 2013, 4, 870-878
“A method for the intracranial delivery of reagents to voltammetric recording sites,” Moquin KF, Jaquins-Gerstl A, and Michael AC J. Neurosci. Methods 2012, 208, 101-107
“Domain-dependent effects of DAT inhibition in the rat dorsal striatum,” Taylor IM, Jaquins-Gerstl, Sesack SR, and Michael AC J. Neurochem 2012, 122, 283-294
“Microdialysis probes alter presynaptic regulation of dopamine terminals in rat striatum,” Wang Y and Michael J. Neurosci. Methods 2012, 208, 34-39