Microdialysis Studies of Seizure-Induced Oxidative Stress

Summary

Principal Investigator: Craig Lunte
Affiliation: University of Kansas
Country: USA
Abstract: We propose to investigate the role of epileptic seizures in oxidative stress. There is a wealth of research that demonstrates epileptic seizures lead to the formation of reactive oxygen species (ROS), which cause oxidative damage to DNA, lipids, and proteins. We intend to investigate the role of excitotoxic catecholamine release during epileptic seizures and their role in the formation of ROS leading to oxidative stress. We will use microdialysis sampling in discrete brain regions along with simultaneous recording of electrocorticographic (ECoG) activity to probe chemical and electrographic activity changes in the brain associated with seizures. This will allow us to correlate biomarker levels with seizure activity. Microdialysis sampling will be used to continuously monitor several biochemical pathways prior to, during, and after induction of seizures. Microdialysis experiments will provide both temporal and spatial information about oxidative stress caused by seizures and the brains response to them. This dual approach will allow us to resolve questions that have remained unclear using plasma and urine sampling and standard tissue sampling techniques. Methods previously developed in the PI's laboratory will be used to monitor formation of ROS, biomarkers for DNA damage, and the neurotransmitter amino acids and catecholamines. New analytical methods will be developed to monitor aldehydes produced through lipid peroxidation, endogenous thiols and disulfides involved in protection from ROS, and prostanoids resulting from arachidonic acid metabolism. Initially, we will use a chemically-induced seizure model using 3-mercaptopropionic acid (3-MPA). Coupled to the advanced analytical methodology and microdialysis sampling, we will then investigate the neurological events leading from seizures to oxidative stress. In particular, the temporal relationship between oxidative stress (as measured by ROS formation), and neuroexcitation (as measured by the GABA/glutamate ratio and the catecholamines) will be determined and correlated to the duration and intensity of seizure episodes.
Funding Period: ----------------2009 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. pmc A parallel dual-electrode detector for capillary electrophoresis
    Megan K Dorris
    Department of Chemistry, Ralph N Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047, USA
    Electrophoresis 33:2725-32. 2012
  2. pmc Microperfusion of 3-MPA into the brain augments GABA
    Andrew P Mayer
    R N Adams Institute for Bioanalytical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA
    Epilepsy Behav 29:478-84. 2013
  3. pmc Correlation of 3-mercaptopropionic acid induced seizures and changes in striatal neurotransmitters monitored by microdialysis
    Eric W Crick
    R N Adams Institute for Bioanalytical Chemistry, Department of Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, United States
    Eur J Pharm Sci 57:25-33. 2014
  4. pmc Investigation of microdialysis sampling calibration approaches for lipophilic analytes: doxorubicin
    Gillian Whitaker
    Department of Chemistry, University of Kansas, RN Adams Institute for Bioanalytical Chemistry, 2030 Becker Drive, Lawrence, KS 66047, USA
    J Pharm Biomed Anal 53:490-6. 2010
  5. pmc Detection of malondialdehyde in vivo using microdialysis sampling with CE-fluorescence
    Justin Carl Cooley
    Department of Chemistry, University of Kansas, Lawrence, KS 66047, USA
    Electrophoresis 32:2994-9. 2011

Detail Information

Publications5

  1. pmc A parallel dual-electrode detector for capillary electrophoresis
    Megan K Dorris
    Department of Chemistry, Ralph N Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047, USA
    Electrophoresis 33:2725-32. 2012
    ..LODs were determined to be as low as 5.0 nM for dual-electrode configuration. Using the dual-potential mode peak identification of targeted phenolic acids in whiskey samples were confirmed based on both migration time and current ratios...
  2. pmc Microperfusion of 3-MPA into the brain augments GABA
    Andrew P Mayer
    R N Adams Institute for Bioanalytical Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, USA
    Epilepsy Behav 29:478-84. 2013
    ....
  3. pmc Correlation of 3-mercaptopropionic acid induced seizures and changes in striatal neurotransmitters monitored by microdialysis
    Eric W Crick
    R N Adams Institute for Bioanalytical Chemistry, Department of Chemistry, University of Kansas, 2030 Becker Drive, Lawrence, KS 66047, United States
    Eur J Pharm Sci 57:25-33. 2014
    ..In vivo microdialysis was combined with electrophysiological methods in order to provide a complete evaluation of the dynamics of the results obtained...
  4. pmc Investigation of microdialysis sampling calibration approaches for lipophilic analytes: doxorubicin
    Gillian Whitaker
    Department of Chemistry, University of Kansas, RN Adams Institute for Bioanalytical Chemistry, 2030 Becker Drive, Lawrence, KS 66047, USA
    J Pharm Biomed Anal 53:490-6. 2010
    ..However, the only point in which no DOX was present in the perfusate was not on the no-net flux line. In addition, the transport of DOX across the microdialysis membrane was considerably slower than the transport of antipyrine...
  5. pmc Detection of malondialdehyde in vivo using microdialysis sampling with CE-fluorescence
    Justin Carl Cooley
    Department of Chemistry, University of Kansas, Lawrence, KS 66047, USA
    Electrophoresis 32:2994-9. 2011
    ..This method provided a limit of detection of 25 nM (S/N=3) and a linear range of 25-2400 nM (1.8-174 ng/mL). This method was used to quantify MDA in rat heart, muscle, liver, and brain dialysate...