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  • 1.
    Hillman, Jan
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Åneman, Oscar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Persson, Mikael
    Anderson, Chris
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Division of dermatology and venereology. Östergötlands Läns Landsting, Centre for Medicine, Department of Dermatology and Venerology in Östergötland.
    Dabrosin, Charlotta
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Biomedicine and Surgery, Oncology. Östergötlands Läns Landsting, Centre of Surgery and Oncology, Department of Oncology UHL.
    Mellergård, Pekka
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Variations in the response of interleukins in neurosurgical intensive care patients monitored using intracerebral microdialysis2007In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 106, no 5, p. 820-825Article in journal (Refereed)
    Abstract [en]

    Object. The aim of this study was to make a preliminary evaluation of whether microdialysis monitoring of cytokines and other proteins in severely diseased neurosurgical patients has the potential of adding significant information to optimize care, thus broadening the understanding of the function of these molecules in brain injury. Methods. Paired intracerebral microdialysis catheters with high-cutoff membranes were inserted in 14 comatose patients who had been treated in a neurosurgical intensive care unit following subarachnoidal hemorrhage or traumatic brain injury. Samples were collected every 6 hours (for up to 7 days) and were analyzed at bedside for routine metabolites and later in the laboratory for interleukin (IL)-1 and IL-6, in two patients, vascular endothelial growth factor and cathepsin-D were also checked. Aggregated microprobe data gave rough estimations of profound focal cytokine responses related to morphological tissue injury and to anaerobic metabolism that were not evident from the concomitantly collected cerebrospinal fluid data. Data regarding tissue with no macroscopic evidence of injury demonstrated that IL release not only is elicited in severely compromised tissue but also may be a general phenomenon in brains subjected to stress. Macroscopic tissue injury was strongly linked to IL-6 but not IL-1b activation. Furthermore, IL release seems to be stimulated by local ischemia. The basal tissue concentration level of IL-1b was estimated in the range of 10 to 150 pg/ml, for IL-6, the corresponding figure was 1000 to 20,000 pg/ml. Conclusions. Data in the present study indicate that catheters with high-cutoff membranes have the potential of expanding microdialysis to the study of protein chemistry as a routine bedside method in neurointensive care.

  • 2.
    Mellergård, Pekka
    et al.
    Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Åneman, Oscar
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Sjögren, Florence
    Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Säberg, Carina
    Östergötlands Läns Landsting, Sinnescentrum, Department of Neurosurgery UHL.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Differences in Cerebral Extracellular Response of Interleukin-1 beta, Interleukin-6, and Interleukin-10 After Subarachnoid Hemorrhage or Severe Head Trauma in Humans2011In: NEUROSURGERY, ISSN 0148-396X, Vol. 68, no 1, p. 12-19Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Microdialysis has become a routine method for biochemical surveillance of patients in neurosurgical intensive care units. OBJECTIVE: To analyze the intracerebral extracellular levels of 3 interleukins (ILs) during the 7 days after major subarachnoid hemorrhage or traumatic brain injury). METHODS: Microdialysate from 145 severely injured neurosurgical intensive care unit patients (88 with subarachnoid hemorrhage, 57 with traumatic brain injury) was collected every 6 hours for 7 days. The concentrations of IL-1 beta and IL-6 were determined by fluorescence multiplex bead technology, and IL-10 was determined by enzyme-linked immunosorbent assay. RESULTS: Presented are the response patterns of 3 ILs during the first week after 2 different types of major brain injury. These patterns are different for each IL and also differ with respect to the kind of pathological impact. For both IL-1 beta and IL-6, the initial peaks (mean values for all patients at day 2 being 26.9 +/- 4.5 and 4399 +/- 848 pg/mL, respectively) were followed by a gradual decline, with IL-6 values remaining 100-fold higher compared with IL-1 beta. Female patients showed a stronger and more sustained response. The response of IL-10 was different, with mean values less than 23 pg/mL and with no significant variation between any of the postimpact days. For all 3 ILs, the responses were stronger in subarachnoid hemorrhage patients. The study also indicates that under normal conditions, IL-1 beta, IL-6, and IL-10 are present only at very low concentrations or not at all in the extracellular space of the human brain. CONCLUSION: This is the first report presenting in some detail the human cerebral response of IL-1 beta, IL-6, and IL-10 after subarachnoid hemorrhage and traumatic brain injury. The 3 ILs have different reaction patterns, with the response of IL-1 beta and IL-6 being related to the type of cerebral damage sustained, whereas the IL-10 response was less varied.

  • 3.
    Mellergård, Pekke
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Åneman, Oscar
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Neuroscience and Locomotion.
    Sjögren, Florence
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Dermatology and Venerology .
    Pettersson, P.
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery . Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Changes in Extracellular Concentrations of Some Cytokines, Chemokines, and Neurotrophic Factors After Insertion of Intracerebral Microdialysis Catheters in Neurosurgical Patients2008In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 62, no 1, p. 151-157Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: The extracellular levels of eight different inflammatory agents were analyzed during the initial 36 hours after insertion of microdialysis catheters in patients. METHODS: Cerebral extracellular fluid from 38 patients who were treated in a neurosurgical intensive care unit for severe brain injury was collected every 6 hours for 36 hours. The concentration of interleukin (IL)-1ß, IL-6, IL-8, macrophage inflammatory protein-1ß, regulated on activation, normal T-cell expressed and secreted (RANTES), fibroblast growth factor-2, and vascular endothelial growth factor was determined by a multiplex assay, and IL-10 was determined by enzyme-linked immunosorbent assay. RESULTS: This is the first report regarding the presence of IL-10, IL-8, macrophage inflammatory protein-1ß, regulated on activation, T-cell expressed and secreted, vascular endothelial growth factor, and fibroblast growth factor-2 in the tissue level proper of the living human brain. The study also provides new information regarding the response of IL-1ß and IL-6 after insertion of a microdialysis catheter. The study confirms that the intriguing patterns of interplay between different components of the inflammatory response studied in laboratory settings are present in the human brain. This was most clearly observed in the variations in response between the three different chemokines investigated, as well as in the rapid and transient response of fibroblast growth factor-2. CONCLUSION: The data presented illustrate the opportunity to monitor biochemical events of possible importance in the human brain and indicate the potential of such monitoring in neurosurgical intensive care. The study also underlines that any analysis of events in the brain involving mechanical invasiveness needs to take into account biochemical changes that are directly related to the manipulation of brain tissue.

  • 4.
    Rejmstad, Peter
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Åkesson, Gustav
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Åneman, Oscar
    Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    A laser Doppler system for monitoring of cerebral microcirculation: implementation and evaluation during neurosurgery2016In: Medical and Biological Engineering and Computing, ISSN 0140-0118, E-ISSN 1741-0444, ISSN 0140-0118, Vol. 54, no 1, p. 123-131Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to adapt and evaluate laser Doppler perfusion monitoring (LDPM) together with custom designed brain probes and software for continuous recording of cerebral microcirculation in patients undergoing neurosurgery. The LDPM system was used to record perfusion and backscattered light (TLI). These parameters were displayed together with the extracted heart rate (HR), pulsatility index (PI) and signal trends from adjustable time intervals. Technical evaluation was done on skin during thermal provocation. Clinical measurements were performed on ten patients undergoing brain tumour surgery. Data from 76 tissue sites were captured with a length varying between 10 s to 15 min. Statistical comparisons were done using Mann-Whitney tests. Grey and tumour tissue could be separated from white matter using the TLI-signal (p < 0.05). The perfusion was significantly higher in grey and tumour tissue compared to white matter (p < 0.005). LDPM was successfully used as an intraoperative tool for monitoring local blood flow and additional parameters linked to cerebral microcirculation (perfusion, TLI, heart rate and PI) during tumour resection. The systems stability opens up for studies in the postoperative care of patients with e.g. traumatic brain injury or subarachnoid haemorrhage.

  • 5.
    Wårdell, Karin
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Rejmstad, Peter
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Åneman, Oscar
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Combined laser Doppler and reflectance spectroscopy measurements during brain surgery2013Conference paper (Other academic)
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