The research in our group concerns the development and applications of techniques for monitoring chemical signals in vivo in the brain, and other organs, by microdialysis, biosensors, and related bioanalytical methods.
The major research interest of our group is the development and applications of techniques, which allow the monitoring of chemical signals in vivo in the brain and other organs. We are particularly interested in minimally invasive techniques, microdialysis, biosensors, and related bioanalytical methods.
The microdialysis technique for the continuous sampling of the interstitial fluid of tissues and organs was developed in our laboratory in the early 1970s and was first published in 1974. Today there are more than 10,000 microdialysis papers published on animal physiology/pharmacology and over 1,000 microdialysis papers on human brain and peripheral organs especially in the fields of intensive care, diabetes, and tissue metabolism.
We are continuing our research on clinical microdialysis with three specific aims:
- To discover and characterize chemical markers of ischemia and cell degradation in microdialysis samples from human tissues and organs.
- To determine the clinical relevance of these markers for the diagnosis and treatment of patients in intensive care.
- To develop clinical routines for the efficient use of microdialysis in the intensive care setting.
Microdialysis provides the very close and reliable chemical correlates to behavioural measures of physiology and pathology of the living body. This fact has made microdialysis especially attractive for use in experimental neuropharmacology, as well as in the clinics.
We have developed several ultra-sensitive HPLC techniques for the determination of trace levels of monoamines and other classical neurotransmitters (acetylcholine, serotonin, noradrenaline, dopamine, histamine, Asp, Glu, Gly, GABA) in the brain microdialysates.
Development of nanoscale bioassay technologies
In continuation of this effort we are carrying out a multi-disciplinary project with the aim to develop nanoscale bioassay technologies based on electrogenerated chemiluminescence, which will allow ultra-sensitive, non-isotopic detection of biomolecules at concentrations bellow 10-12 M and in 100-200 nl sample volumes.
Reagents utilizing electrochemically generated luminescence of novel tris(2,2´-bipyridyl)ruthenium(II) molecular labels have been synthesized and are used as labels for monoamines and neuropeptides.
Biological diagnostic tools using microsystems and supersensitive magnetic detection
In parallel to our research on neurochemical monitoring techniques, we have initiated a series of studies on the applications of functionalized superparamagnetic nanoparticles as specific contrast enhancers in magnetic resonance imaging (MRI).
Initially, we have focused on nanoparticle-based labelling and tracking of stem cells transplanted into the brain or spinal cord. Current research objectives are:
- To examine the possibilities of using functionalized nanoparticles for labelling amyloid plaques in animal models of Alzheimer's disease
- To develop and evaluate long-circulating blood pool agents, which will allow enhanced sensitivity for measurements of drug effects in pharmacological MRI
- Initiate studies on controlled drug release from specially-designed nanoparticles aiming for brain targeting.
All the projects require a multidisciplinary effort and imply active interaction and collaboration with clinicians, organic chemists, materials chemistry scientists, physicists and engineers, experimental MRI scientists, as well as with industrial partners.
Jan Kehr – Senior researcher
Takashi Yoshitake – Senior researcher
Shimako Yoshitake – Senior researcher
- Microdialysis monitoring of ischemia in brain and peripheral organs during intensive care.
- Development of nanoscale bioassay technologies based on electrogenerated chemiluminescence.
- Biological diagnostic tools using microsystems and supersensitive magnetic detection.
The Ginkgo biloba extract EGb 761(R) and its main constituent flavonoids and ginkgolides increase extracellular dopamine levels in the rat prefrontal cortex.
Yoshitake T, Yoshitake S, Kehr J
Br. J. Pharmacol. 2010 Feb;159(3):659-68
Determination of Histamine in Rat Plasma and Tissue Extracts by Intramolecular Excimer-Forming Derivatization and LC with Fluorescence Detection.
Ichinose F, et al.
Chromatographia 70: 575-580, 2009
Intra- and intermolecular interaction ECL study of novel ruthenium tris-bipyridyl complexes with different amine reductants.
Sun S, Yang Y, Liu F, Fan J, Peng X, Kehr J, et al
Dalton Trans 2009 Oct;(38):7969-74
The role of 5-HT(1A) receptors in learning and memory.
Ogren SO, Eriksson TM, Elvander-Tottie E, D'Addario C, Ekström JC, Svenningsson P, et al
Behav. Brain Res. 2008 Dec;195(1):54-77
From the Golgi-Cajal mapping to the transmitter-based characterization of the neuronal networks leading to two modes of brain communication: wiring and volume transmission.
Fuxe K, Dahlström A, Höistad M, Marcellino D, Jansson A, Rivera A, et al
Brain Res Rev 2007 Aug;55(1):17-54
Effects of the 5-HT1B receptor antagonist NAS-181 on extracellular levels of acetylcholine, glutamate and GABA in the frontal cortex and ventral hippocampus of awake rats: a microdialysis study.
Hu XJ, Wang FH, Stenfors C, Ogren SO, Kehr J
Eur Neuropsychopharmacol 2007 Sep;17(9):580-6
Continuous delivery of rotigotine decreases extracellular dopamine suggesting continuous receptor stimulation.
Kehr J, Hu XJ, Goiny M, Scheller DK
J Neural Transm (Vienna) 2007 ;114(8):1027-31
Determination of the dopamine agonist rotigotine in microdialysates from the rat brain by microbore column liquid chromatography with electrochemical detection.
Kehr J, Hu XJ, Yoshitake T, Scheller D
J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2007 Jan;845(1):109-13
The neuropeptide galanin as an in vivo modulator of brain 5-HT1A receptors: possible relevance for affective disorders.
Ogren SO, Razani H, Elvander-Tottie E, Kehr J
Physiol. Behav. 2007 Sep;92(1-2):172-9
Reciprocal effects of combined administration of serotonin, noradrenaline and dopamine reuptake inhibitors on serotonin and dopamine levels in the rat prefrontal cortex: the role of 5-HT1A receptors.
Weikop P, Kehr J, Scheel-Krüger J
J. Psychopharmacol. (Oxford) 2007 Nov;21(8):795-804
Differential effects of adjunctive methylphenidate and citalopram on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain.
Weikop P, Yoshitake T, Kehr J
Eur Neuropsychopharmacol 2007 Oct;17(10):658-71