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Sensors for brain mapping
Journal of Neuroscience Methods 109 (2001) 1 – 2 www.elsevier.com/locate/jneumeth
Foreword
Sensors for brain mapping
Fig. 1. The participants of the symposium ‘Sensors for Brain Mapping’, in front of the Trolleholm castle.
The papers in this special issue of the Journal of Neuroscience Methods have been submitted by invited speakers at the symposium ‘Sensors for Brain Mapping’, held in Lund, Sweden, June 6 – 8, 2000 (Fig. 1). These original contributions summarise many of the new topics discussed at the meeting. The meeting was organised by the University of Lund, Wallenberg Neuroscience Centre in Lund and the Karolinska Institutet in Stockholm. The purpose of this inter-disciplinary meeting was to create a forum, which would (1) summarise the state-of-the-art in applications of minimal invasive sensor technologies in the experimental and clinical neurosciences, and at the same time, (2) pointout a growing importance of nanotechnology, micromechanics, microfluidics and nano-structured materials for the design of novel in vivo monitoring devices. The first area was well represented by the techniques such as in vivo microdialysis and in vivo voltammetry, and in fact, most of the presentations at the meeting were focused on various aspects of microdialysis sampling or electrochemical sensing devices, as Pete Kissinger stressed in his opening lecture.
Today, most of the pharmaceutical companies active in the CNS therapeutic area utilise microdialysis as a research tool to obtain neurochemical correlates to various behavioural tests or pharmacological treatments. There is an increasing frequency of microdialysis data in the patent literature on new drugs and therapies or in the respective IND and NDA files. However, the question still remains — how good and reliable are the microdialysis data and to what extent do they influence the final decision to ‘go’ or ‘not go’ to the Phase I trials? This issue was addressed in two sessions focused on neurodegenerative and mental diseases. The benefits of microdialysis in the process of drug discovery were discussed by Ezio Giacobini (cholinesterase inhibitors, Alzheimer’s disease) Adrian Carter (Huntington’s disease, stroke), Hans Rollema (depression, schizophrenia) and Jørn Arnt (schizophrenia, relevance to behavioural models). In subsequent presentations, Giancarlo Pepeu described animal models of brain inflammation for testing the efficacy of anti-inflammatory drugs in the treatment of Alzheimer’s disease. Greg Gerhardt used in vivo
0165-0270/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII: S0165-0270(01)00394-6
2
Editorial
chronoamperometry and Pekka Ma¨ nnisto¨ applied microdialysis in animal models of Parkinson’s disease, for studies of new therapeutic strategies based on GDNF or COMT inhibitors, respectively. The in vivo imaging of neural tissue transplants in Parkinson’s disease and in animal models was presented by Ha˚ kan Widner and the use of intraspinal microdialysis to monitor grafted monoaminergic neurons was presented by Giampiero Leanza. The use of brain microdialysis in a kindling model of epilepsy was presented by Merab Kokaia. The topic of neuroprotection in animal models was discussed by Adrian Carter in his lecture on malonate-induced cytotoxic lesions and by Yvette Michotte who used the endothelin-1 model of focal ischemia. In addition, in a separate session on clinical microdialysis, Urban Ungerstedt and Lars Hillered summarised the recent status of intracerebral microdialysis in humans following stroke or traumatic brain injuries. Microdialysis, in a combination of two probes or one probe and one infusion cannula, has been shown to serve as an excellent tool for in vivo studies of functional neuroanatomy, neuronal circuits and interactions between neurotransmitter systems. Ben Westerink, William O’Connor and Jan Kehr discussed these features of the technique and the applications in basic research. Ben gave a general overview on the use of dual-probe microdialysis with a recent focus on evaluation of diffusion kinetics of drugs infused via the first probe, inducing release of dopamine at the distal probe. Billy O’Connor presented his data on GABA with dual-probe microdialysis in the mesocortico-limbic circuit. Jan Kehr discussed the effects of intraventricularly injected peptide galanin on release of acetylcholine, serotonin and noradrenaline with special focus on the use of microdialysis in awake transgenic mice. The session on progress in sensor technologies and monitoring cellular microenvironment was initiated by Mark Wightman who presented a summary on his work with carbon-fibre microelectrodes and fast scan voltammetry. Francesco Crespi discussed the possibilities of using voltammetry for detection of NO or nitrites and Adrian Michael brought-up the topic of biosensors, exemplified by a sensor for glutamate based on electropolymerisation and immobilisation of glutamate oxidase on a carbon fibre microelectrode. In a special lecture, Alexander Netrusov described the properties of newly purified glutamate oxidase. Carbon fibers offer a number of exciting applications such as scanning electrochemical microscopy, as stressed-out by Albert Schulte in his lecture, with nano-technologies developed for shaping of carbon fibres, which could be of interest for in vivo applications. Jonas Bergquist gave a ‘Swedish smo¨ rga˚ sbord-type’ lecture presenting the applications of mass spectrometry for construction of protein maps, e.g. of brain tissue, and a combination .
of MS with microseparation techniques such as 2-dimensional gel electrophoresis, CE or HPLC. Susan Lunte described the advantages of combing in vivo microdialysis with electrochemical detection and laserinduced detection for investigations of the activity of peptidases, in this case formation of fragments from infused substance P. The unique features of micro-machined devices were further analysed in the session on nanotechnology in the biosciences. Albert van der Berg presented the concept of the mTAS (micro total analysis system) and the latest development in microfluidics devices, whereas Thomas Laurell described his research both with the (glucose) sensor and lately, the construction of piezoelectric dispensing unit using silicon microstructures, which allowed dispensing of volumes down to 60 pl for analysis by MALDI MS. Besides the lectures, about a dozen posters were presented, dealing with various aspects of biosensor construction, characterisation and applications. On the last day, the participants had a chance to visit the laboratories of Wallenberg Neuroscience Center, particularly the groups headed by Professors Anders Bjo¨ rklund and Olle Lindvall. The meetings top social moment was a dinner in the historical Trolleholm castle at the countryside nearby Lund. Besides the information value of all the scientific contributions, several interesting new contacts were established, and from this point of view, it was generally agreed, the meeting was successful and fulfilled its mission. We hope that this special issue is helpful to many scientists who were unable to participate in this unique meeting.
Acknowledgements The organisers Elisabeth Csoregi, Tautgirdas Ruzgas (Lund University), Merab and Zaal Kokaia (Wallenberg Neuroscience Center) and Jan Kehr (Karolinska Institutet) would like to thank the following for providing financial support: Swedish Medical Research Council (MFR), Swedish Natural Science Research Council (NFR), Swedish Council for Engineering Sciences (TFR), Swedish National Board for Industrial and Technical Development (NUTEK), CMA/Microdialysis AB, Sweden, Pfizer Inc., USA, Boehringer Ingelheim KG, Germany. A special thanks to Tamara Landia for making a web-site and other printed materials for the conference and Professor Christopher Brett for the photography. Jan Kehr Department of Neuroscience, Karolinska Institutet, Doktorsringen 12, plan 6, 171 77 Stockholm, Sweden E-mail: [email protected]
Foreword
Sensors for brain mapping
Fig. 1. The participants of the symposium ‘Sensors for Brain Mapping’, in front of the Trolleholm castle.
The papers in this special issue of the Journal of Neuroscience Methods have been submitted by invited speakers at the symposium ‘Sensors for Brain Mapping’, held in Lund, Sweden, June 6 – 8, 2000 (Fig. 1). These original contributions summarise many of the new topics discussed at the meeting. The meeting was organised by the University of Lund, Wallenberg Neuroscience Centre in Lund and the Karolinska Institutet in Stockholm. The purpose of this inter-disciplinary meeting was to create a forum, which would (1) summarise the state-of-the-art in applications of minimal invasive sensor technologies in the experimental and clinical neurosciences, and at the same time, (2) pointout a growing importance of nanotechnology, micromechanics, microfluidics and nano-structured materials for the design of novel in vivo monitoring devices. The first area was well represented by the techniques such as in vivo microdialysis and in vivo voltammetry, and in fact, most of the presentations at the meeting were focused on various aspects of microdialysis sampling or electrochemical sensing devices, as Pete Kissinger stressed in his opening lecture.
Today, most of the pharmaceutical companies active in the CNS therapeutic area utilise microdialysis as a research tool to obtain neurochemical correlates to various behavioural tests or pharmacological treatments. There is an increasing frequency of microdialysis data in the patent literature on new drugs and therapies or in the respective IND and NDA files. However, the question still remains — how good and reliable are the microdialysis data and to what extent do they influence the final decision to ‘go’ or ‘not go’ to the Phase I trials? This issue was addressed in two sessions focused on neurodegenerative and mental diseases. The benefits of microdialysis in the process of drug discovery were discussed by Ezio Giacobini (cholinesterase inhibitors, Alzheimer’s disease) Adrian Carter (Huntington’s disease, stroke), Hans Rollema (depression, schizophrenia) and Jørn Arnt (schizophrenia, relevance to behavioural models). In subsequent presentations, Giancarlo Pepeu described animal models of brain inflammation for testing the efficacy of anti-inflammatory drugs in the treatment of Alzheimer’s disease. Greg Gerhardt used in vivo
0165-0270/01/$ - see front matter © 2001 Elsevier Science B.V. All rights reserved. PII: S0165-0270(01)00394-6
2
Editorial
chronoamperometry and Pekka Ma¨ nnisto¨ applied microdialysis in animal models of Parkinson’s disease, for studies of new therapeutic strategies based on GDNF or COMT inhibitors, respectively. The in vivo imaging of neural tissue transplants in Parkinson’s disease and in animal models was presented by Ha˚ kan Widner and the use of intraspinal microdialysis to monitor grafted monoaminergic neurons was presented by Giampiero Leanza. The use of brain microdialysis in a kindling model of epilepsy was presented by Merab Kokaia. The topic of neuroprotection in animal models was discussed by Adrian Carter in his lecture on malonate-induced cytotoxic lesions and by Yvette Michotte who used the endothelin-1 model of focal ischemia. In addition, in a separate session on clinical microdialysis, Urban Ungerstedt and Lars Hillered summarised the recent status of intracerebral microdialysis in humans following stroke or traumatic brain injuries. Microdialysis, in a combination of two probes or one probe and one infusion cannula, has been shown to serve as an excellent tool for in vivo studies of functional neuroanatomy, neuronal circuits and interactions between neurotransmitter systems. Ben Westerink, William O’Connor and Jan Kehr discussed these features of the technique and the applications in basic research. Ben gave a general overview on the use of dual-probe microdialysis with a recent focus on evaluation of diffusion kinetics of drugs infused via the first probe, inducing release of dopamine at the distal probe. Billy O’Connor presented his data on GABA with dual-probe microdialysis in the mesocortico-limbic circuit. Jan Kehr discussed the effects of intraventricularly injected peptide galanin on release of acetylcholine, serotonin and noradrenaline with special focus on the use of microdialysis in awake transgenic mice. The session on progress in sensor technologies and monitoring cellular microenvironment was initiated by Mark Wightman who presented a summary on his work with carbon-fibre microelectrodes and fast scan voltammetry. Francesco Crespi discussed the possibilities of using voltammetry for detection of NO or nitrites and Adrian Michael brought-up the topic of biosensors, exemplified by a sensor for glutamate based on electropolymerisation and immobilisation of glutamate oxidase on a carbon fibre microelectrode. In a special lecture, Alexander Netrusov described the properties of newly purified glutamate oxidase. Carbon fibers offer a number of exciting applications such as scanning electrochemical microscopy, as stressed-out by Albert Schulte in his lecture, with nano-technologies developed for shaping of carbon fibres, which could be of interest for in vivo applications. Jonas Bergquist gave a ‘Swedish smo¨ rga˚ sbord-type’ lecture presenting the applications of mass spectrometry for construction of protein maps, e.g. of brain tissue, and a combination .
of MS with microseparation techniques such as 2-dimensional gel electrophoresis, CE or HPLC. Susan Lunte described the advantages of combing in vivo microdialysis with electrochemical detection and laserinduced detection for investigations of the activity of peptidases, in this case formation of fragments from infused substance P. The unique features of micro-machined devices were further analysed in the session on nanotechnology in the biosciences. Albert van der Berg presented the concept of the mTAS (micro total analysis system) and the latest development in microfluidics devices, whereas Thomas Laurell described his research both with the (glucose) sensor and lately, the construction of piezoelectric dispensing unit using silicon microstructures, which allowed dispensing of volumes down to 60 pl for analysis by MALDI MS. Besides the lectures, about a dozen posters were presented, dealing with various aspects of biosensor construction, characterisation and applications. On the last day, the participants had a chance to visit the laboratories of Wallenberg Neuroscience Center, particularly the groups headed by Professors Anders Bjo¨ rklund and Olle Lindvall. The meetings top social moment was a dinner in the historical Trolleholm castle at the countryside nearby Lund. Besides the information value of all the scientific contributions, several interesting new contacts were established, and from this point of view, it was generally agreed, the meeting was successful and fulfilled its mission. We hope that this special issue is helpful to many scientists who were unable to participate in this unique meeting.
Acknowledgements The organisers Elisabeth Csoregi, Tautgirdas Ruzgas (Lund University), Merab and Zaal Kokaia (Wallenberg Neuroscience Center) and Jan Kehr (Karolinska Institutet) would like to thank the following for providing financial support: Swedish Medical Research Council (MFR), Swedish Natural Science Research Council (NFR), Swedish Council for Engineering Sciences (TFR), Swedish National Board for Industrial and Technical Development (NUTEK), CMA/Microdialysis AB, Sweden, Pfizer Inc., USA, Boehringer Ingelheim KG, Germany. A special thanks to Tamara Landia for making a web-site and other printed materials for the conference and Professor Christopher Brett for the photography. Jan Kehr Department of Neuroscience, Karolinska Institutet, Doktorsringen 12, plan 6, 171 77 Stockholm, Sweden E-mail: [email protected]