title: Simultaneous monitoring of potassium, glucose and lactate during spreading depolarization in the injured human brain - Proof of principle of a novel real-time neurochemical analysis system, continuous online microdialysis.
abstract: Spreading depolarizations occur spontaneously and frequently in injured human brain. They propagate slowly through injured tissue often cycling around a local area of damage. Tissue recovery after an spreading depolarization requires greatly augmented energy utilisation to normalise ionic gradients from a virtually complete loss of membrane potential. In the injured brain, this is difficult because local blood flow is often low and unreactive. In this study, we use a new variant of microdialysis, continuous on-line microdialysis, to observe the effects of spreading depolarizations on brain metabolism. The neurochemical changes are dynamic and take place on the timescale of the passage of an spreading depolarization past the microdialysis probe. Dialysate potassium levels provide an ionic correlate of cellular depolarization and show a clear transient increase. Dialysate glucose levels reflect a balance between local tissue glucose supply and utilisation. These show a clear transient decrease of variable magnitude and duration. Dialysate lactate levels indicate non-oxidative metabolism of glucose and show a transient increase. Preliminary data suggest that the transient changes recover more slowly after the passage of a sequence of multiple spreading depolarizations giving rise to a decrease in basal dialysate glucose and an increase in basal dialysate potassium and lactate levels.
authors: 1 Department of Bioengineering, Imperial College, London, UK.
authors: Michelle L
authors: ML
authors: Rogers
authors: 1 Department of Bioengineering, Imperial College, London, UK.
authors: Chi Leng
authors: CL
authors: Leong
authors: 1 Department of Bioengineering, Imperial College, London, UK.
authors: Sally An
authors: SA
authors: Gowers
authors: 1 Department of Bioengineering, Imperial College, London, UK.
authors: Isabelle C
authors: IC
authors: Samper
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.
authors: Sharon L
authors: SL
authors: Jewell
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.
authors: Asma
authors: A
authors: Khan
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.
authors: Leanne
authors: L
authors: McCarthy
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.|3 King's College Hospital NHS Foundation Trust, London, UK.
authors: Clemens
authors: C
authors: Pahl
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.|3 King's College Hospital NHS Foundation Trust, London, UK.
authors: Christos M
authors: CM
authors: Tolias
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.|3 King's College Hospital NHS Foundation Trust, London, UK.
authors: Daniel C
authors: DC
authors: Walsh
authors: 2 Department of Basic and Clinical Neuroscience, King's College, London, UK.
authors: Anthony J
authors: AJ
authors: Strong
authors: 1 Department of Bioengineering, Imperial College, London, UK.
authors: Martyn G
authors: MG
authors: Boutelle
mesh_terms: D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D003128:Coma / Q000378:metabolism / Q000503:physiopathology; D013181:Cortical Spreading Depression / Q000502:physiology*; D000069280:Electrocorticography; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism*; D017551:Microdialysis; D064926:Neurophysiological Monitoring / Q000379:methods*; D009862:Online Systems; D011188:Potassium / Q000378:metabolism*
chemical_list: D019344:Lactic Acid; D005947:Glucose; D011188:Potassium
keywords: On-line microdialysis; ischaemic brain injury; microfluidics; neurometabolic coupling; spreading depolarization