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  • 1.
    Björklund, Martin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Radovanovic, S
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Ljubisavljevic, M
    Windhorst, U
    Johansson, H
    Muscle stretch-induced modulation of noxiously activated dorsal horn neurons of feline spinal cord2004In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 48, no 2, p. 175-184Article in journal (Refereed)
    Abstract [en]

    The present work was designed to check for the possibility of interactions between mechanical innocuous and chemically induced noxious muscle afferent inputs on discharge behavior of nociceptive superficial dorsal horn neurons (SDHNs) of the spinal cord in decerebrated cats. The innocuous and noxious stimuli were applied separately and in combination, so that the effects of the innocuous stimulus on nociceptive processing could be evaluated. The innocuous stimulus consisted of ramp-and-hold stretches of the gastrocnemius muscles, whereas the noxious stimulus consisted of i.a. injections of bradykinin (BK; 0.5-1 ml, 50 microg/ml) into the arterial circulation of same muscles. Only neurons up to approximately 1mm depth and those that responded to noxious pinch of the gastrocnemius muscles were selected for further analysis. The activity of 16 dorsal horn neurons was recorded extracellularly with high-impedance glass microelectrodes, out of which seven responded to stretch, while 12 neurons responded to bradykinin injections. The bradykinin injections induced three types of responses: excitatory, inhibitory and mixed. The majority of the neurons that showed excitatory and mixed responses to bradykinin were also influenced by stretches applied directly after the bradykinin injection. In these neurons, the stretch usually counteracted the bradykinin-induced response, i.e. shortening and reducing bradykinin-induced excitation and re-exciting the cells after bradykinin-induced inhibition. The mechanism of the stretch modulation is proposed to reside in a segmental spinal control of the nociceptive transmission.

  • 2.
    Brohlin, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Mahay, Daljeet
    Novikov, Lev N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Terenghi, Giorgio
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Shawcross, Susan G
    Novikova, Liudmila N
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy.
    Characterisation of human mesenchymal stem cells following differentiation into Schwann cell-like cells2009In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 64, no 1, p. 41-49Article in journal (Refereed)
    Abstract [en]

    Cell-based therapies provide a clinically applicable and available alternative to nerve autografts. Our previous studies have characterised rat-derived mesenchymal stem cells (MSC) and here we have investigated the phenotypic, molecular and functional characteristics of human-derived MSC (hMSC) differentiated along a Schwann cell lineage. The hMSC were isolated from healthy human donors and the identity of the undifferentiated hMSC was confirmed by the detection of MSC specific cells surface markers. The hMSC were differentiated along a glial cell lineage using an established cocktail of growth factors including glial growth factor-2. Following differentiation, the hMSC expressed the key Schwann cell (SC) markers at both the transcriptional and translational level. More importantly, we show the functional effect of hMSC on neurite outgrowth using an in vitro co-culture model system with rat-derived primary sensory neurons. The number of DRG sprouting neurites was significantly enhanced in the presence of differentiated hMSC; neurite length and density (branching) were also increased. These results provide evidence that hMSC can undergo molecular, morphological and functional changes to adopt a SC-like behaviour and, therefore, could be suitable as SC substitutes for nerve repair in clinical applications.

  • 3.
    Forsman, Lea J
    et al.
    Neuropediatric Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet and Stockholm Brain Institute, SE-171 76, Sweden.
    de Manzano, Örjan
    Neuropediatric Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet and Stockholm Brain Institute, SE-171 76, Sweden.
    Karabanov, Anke
    Neuropediatric Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet and Stockholm Brain Institute, SE-171 76, Sweden.
    Madison, Guy
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Ullén, Fredrik
    Neuropediatric Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet and Stockholm Brain Institute, SE-171 76, Sweden.
    Differences in regional brain volume related to the extraversion–introversion dimension: a voxel based morphometry study2012In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 72, no 1, p. 59-67Article in journal (Refereed)
    Abstract [en]

    Extraverted individuals are sociable, behaviorally active, and happy. We report data from a voxel based morphometry study investigating, for the first time, if regional volume in gray and white matter brain regions is related to extraversion. For both gray and white matter, all correlations between extraversion and regional brain volume were negative, i.e. the regions were larger in introverts. Gray matter correlations were found in regions that included the right prefrontal cortex and the cortex around the right temporo–parietal junction – regions that are known to be involved in behavioral inhibition, introspection, and social-emotional processing, e.g. evaluation of social stimuli and reasoning about the mental states of others. White matter correlations extended from the brainstem to widespread cortical regions, and were largely due to global effects, i.e. a larger total white matter volume in introverts. We speculate that these white matter findings may reflect differences in ascending modulatory projections affecting cortical regions involved in behavioral regulation.

  • 4.
    Reid, Adam J
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Shawcross, Susan G
    Hamilton, Alex E
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Wiberg, Mikael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Anatomy. Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Hand Surgery.
    Terenghi, Giorgio
    N-acetylcysteine alters apoptotic gene expression in axotomised primary sensory afferent subpopulations.2009In: Neuroscience research, ISSN 0168-0102, E-ISSN 1872-8111, Vol. 65, no 2, p. 148-155Article in journal (Refereed)
    Abstract [en]

    Novel approaches are required in peripheral nerve injury management because current surgical techniques, which do not address axotomy-induced neuronal death, lead to deficient sensory recovery. Sensory neuronal death has functional preference with cutaneous neurons dying in great numbers whilst muscle afferents survive axotomy. This offers the potential of comparing similar cell types that suffer distinct fates upon nerve injury. Here, a novel approach, combining in vivo rat nerve injury model with laser microdissection and quantitative real-time polymerase chain reaction, identifies crucial disparities in apoptotic gene expression attributable to subpopulations of differing sensory modalities and examines the response to N-acetylcysteine (NAC) therapy. We show that axotomised muscle afferent neurons survive injury due to a neuroprotective response which markedly downregulates Bax and caspase-3 mRNA. In contrast, axotomised cutaneous sensory neurons significantly upregulate caspase-3 and alter both Bcl-2 and Bax expression such that pro-apoptotic Bax predominates. N-Acetylcysteine (NAC) intervention promotes neuroprotection of cutaneous sensory neurons through considerable upregulation of Bcl-2 and downregulation of both Bax and caspase-3 mRNA. The data presented identifies differential activation of apoptotic genes in axotomised neuronal subpopulations. Furthermore, NAC therapy instigates apoptotic gene expression changes in axotomised neurons, thereby offering pharmacotherapeutic potential in the clinical treatment of nerve injury.

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