| 11. |
- Brohlin, Maria, et al.
(författare)
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Aging effect on neurotrophic activity of human mesenchymal stem cells
- 2012
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Ingår i: PLOS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:9, s. e45052-
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Tidskriftsartikel (refereegranskat)abstract
- Clinical efficacy of stem cells for nerve repair is likely to be influenced by issues including donor age and in vitro expansion time. We isolated human mesenchymal stem cells (MSC) from bone marrow of young (16–18 years) and old (67–75 years) donors and analyzed their capacity to differentiate and promote neurite outgrowth from dorsal root ganglia (DRG) neurons. Treatment of MSC with growth factors (forskolin, basic fibroblast growth factor, platelet derived growth factor-AA and glial growth factor-2) induced protein expression of the glial cell marker S100 in cultures from young but not old donors. MSC expressed various neurotrophic factor mRNA transcripts. Growth factor treatment enhanced the levels of BDNF and VEGF transcripts with corresponding increases in protein release in both donor cell groups. MSC in co-culture with DRG neurons significantly enhanced total neurite length which, in the case of young but not old donors, was further potentiated by treatment of the MSC with the growth factors. Stem cells from young donors maintained their proliferation rate over a time course of 9 weeks whereas those from the old donors showed increased population doubling times. MSC from young donors, differentiated with growth factors after long-term culture, maintained their ability to enhance neurite outgrowth of DRG. Therefore, MSC isolated from young donors are likely to be a favourable cell source for nerve repair.
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| 12. |
- Brohlin, Maria
(författare)
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Mesenchymal stem cells for repair of the peripheral and central nervous system
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bone marrow-derived mesenchymal stem cells (MSC) have been shown to provide neuroprotection after transplantation into the injured nervous system. The present thesis investigates whether adult human and rat MSC differentiated along a Schwann cell lineage could increase their expression of neurotrophic factors and promote regeneration after transplantation into the injured peripheral nerve and spinal cord. Human and rat mesenchymal stem cells (hMSC and rMSC) expressed characteristic stem cell surface markers, mRNA transcripts for different neurotrophic factors and demonstrated multi-lineage differentiation potential. Following treatment with a cocktail of growth factors, the hMSC and rMSC expressed typical Schwann cells markers at both the transcriptional and translational level and significantly increased production of brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF). Age and time in culture are of relevance for clinical settings and growth-promoting effects of hMSC from young donors (16-18 years) and old donors (67-75 years) were compared. Undifferentiated hMSC from both young and old donors increased total neurite length of cultured dorsal root ganglion (DRG) neurons. Differentiation of hMSC from the young donors, but not the eldery donors, further enhanced the neurite outgrowth. Undifferentiated hMSC were cultured for eleven weeks in order to examine the effect of in vitro expansion time on neurite outgrowth. hMSC from the young donors maintained their proliferation rate and their ability to enhance neurite outgrowth from DRG neurons. Using a sciatic nerve injury model, a 10mm gap was bridged with either an empty tubular fibrin glue conduit, or conduits containing hMSC, with and without cyclosporine treatment. Cells were labeled with PKH26 prior to transplantation. At 3 weeks after injury the conduits with cells and immunosuppression increased regeneration compared with an empty conduit. PKH26 labeled human cells survived in the rat model and the inflammatory reaction could be suppressed by cyclosporine. After cervical C4 hemisection, BrdU/GFP-labeled rMSC were injected into the lateral funiculus rostral and caudal to the spinal cord lesion site. Spinal cords were analyzed 2-8 weeks after transplantation. Transplanted MSC remained at the injection sites and in the trauma zone for several weeks and were often associated with numerous neurofilament-positive axons. Transplanted rMSC induced up-regulation of vascular endothelial growth factor in spinal cord tissue rostral to the injury site, but did not affect expression of brain-derived neurotrophic factor. Although rMSC provided neuroprotection for rubrospinal neurons and significantly attenuated astroglial and microglial reaction, cell transplantation caused aberrant sprouting of calcitonin gene-related peptide immunostained sensory axons in the dorsal horn. In summary these results demonstrate that both rat and human MSC can be differentiated towards the glial cell lineage, and show functional characteristics similar to Schwann cells. hMSC from the young donors represent a more favorable source for neurotransplantation since they maintain proliferation rate and preserve their growth-promoting effects in long-term cultures. The data also suggest that differentiated MSC increase expression of neurotrophic factors and support regeneration after peripheral nerve and spinal cord injury.
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| 13. |
- Carelli, Maria Grazia, 1959-, et al.
(författare)
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Time out of mind : temporal perspective in adults with ADHD
- 2012
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Ingår i: Journal of Attention Disorders. - : SAGE. - 1087-0547 .- 1557-1246. ; 16:6, s. 460-466
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Tidskriftsartikel (refereegranskat)abstract
- Objective: ADHD is often associated with difficulties in planning and time management. In this study, the authors examined the hypothesis that these functional problems in ADHD reflect systematic biases in temporal orientation.Method: To test this hypothesis, adults with ADHD (n = 30) and healthy controls (n = 60) completed the Swedish version of the Zimbardo Time Perspective Inventory (S-ZTPI).Results: Although a majority of the ADHD participants were tested under stimulant medication, they showed significant differences in all the six subscales of the S-ZTPI. Logistic regression analysis, with age, education, depression, and response inhibition as covariates, showed that the Future Positive Scale was the primary predictor of ADHD status.Conclusion: These findings suggest that ADHD is associated with systematic biases in habitual time orientation and that these differences may contribute to functional problems in ADHD.
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| 14. |
- Ek, Lena, 1961-, et al.
(författare)
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Early cognitive impairment in a subset of patients with presumed low-grade glioma
- 2010
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Ingår i: Neurocase. - : Informa UK Limited. - 1355-4794 .- 1465-3656. ; 16:6, s. 503-511
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Tidskriftsartikel (refereegranskat)abstract
- We investigated the presence of cognitive impairment, in adults with presumed low-grade glioma at early stage of disease prior to major treatments, in relation to neurological symptoms and radiological characteristics of the tumour. Sixteen patients were evaluated. A subset of patients was identified with clearly impaired cognition. Patients with cognitive impairment often had large tumours in the left frontal lobe, were relatively young, and most of them were males. We conclude that cognitive dysfunction may be present already at early stage of disease, and that early identification of patients at risk is warranted.
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| 15. |
- Fahnehjelm, Kristina Teär, et al.
(författare)
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Visual function, ocular motility and ocular characteristics in patients with mitochondrial complex I deficiency
- 2012
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Ingår i: Acta ophthalmologica. - : Wiley. - 1755-3768 .- 1755-375X. ; 90:1, s. 32-43
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Purpose: The aims of the present study were to investigate visual function, ocular motility and ocular characteristics in children and young adults with complex I deficiency. Material and Methods: In a prospective study with longitudinal follow-up, the visual and ocular outcome in 13 patients with deficiency in complex I [nicotine-amide adenine dinucleotide (NADH) dehydrogenase] in the mitochondrial respiratory chain is presented. The patients were diagnosed during 1995-2007 and assessed during 1997-2009 at a median age of 12.8 years (range 3.1-23.4). Results: Twelve of 13 patients had visual impairment and/or ocular pathology. Four of 10 patients who co-operated in visual assessment had a best corrected decimal visual acuity of A mutation in mitochondrial DNA. Only one patient had normal visual acuity and ocular outcome including refraction and visual fields. Follow-up time was median 3.0 years (range 0-11). Conclusion: Visual impairment, ocular motility problems and OA are common in children and young adults with complex I deficiency and should prompt the paediatric ophthalmologist to consider mitochondrial disorders.
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| 16. |
- Hellberg, Matthias, et al.
(författare)
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Small Distal Muscles and Balance Predict Survival in End-Stage Renal Disease.
- 2014
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Ingår i: Nephron Clinical Practice. - : S. Karger AG. - 1660-2110. ; 126:3, s. 116-123
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Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Survival for patients on renal replacement therapy (RRT) has been shown to correlate to the level of physical activity and exercise capacity. We examined whether composite measures of functional status at the start of RRT predict survival. Methods: In this retrospective study, the same physiotherapist, using a standardized battery of tests for functional status, tested 134 patients at the start of RRT. Results: At the end of the observation period, 112 patients (84%) were still alive. Age (p < 0.0001), co-morbidity (p = 0.028), hand grip strength (right: p = 0.0065; left: p = 0.0039), standing heel rise (right: p = 0.011; left: p = 0.004) and functional reach (p = 0.015) were significant predictors of survival. After adjustment for sex, age and co-morbidity, hand grip strength left (p = 0.023) was a significant predictor of survival. Conclusion: Hand grip strength, standing heel rise and functional reach at the start of RRT seem to affect survival. A 50% reduction in hand grip strength left was associated with an almost 3-fold increase in mortality. Deterioration of function in small distal muscles and balance may be early signs of uraemic myopathy. A relatively simple and clinically feasible battery of tests can help detect patients at risk. © 2014 S. Karger AG, Basel.
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| 17. |
- Howner, Katarina, et al.
(författare)
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Thinner cortex in the frontal lobes in mentally disordered offenders
- 2012
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Ingår i: Psychiatry Research. - : Elsevier BV. - 0165-1781 .- 1872-7123 .- 0925-4927. ; 203:2-3, s. 126-131
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Tidskriftsartikel (refereegranskat)abstract
- Antisocial and violent behaviour have been associated with both structural and functional brain abnormalities in the frontal and the temporal lobes. The aim of the present study was to assess cortical thickness in offenders undergoing forensic psychiatric assessments, one group with psychopathy (PSY, n = 7) and one group with autism spectrum disorder (ASD, n = 7) compared to each other as well as to a reference group consisting of healthy non-criminal subjects (RG, n = 12). A second aim was to assess correlation between scores on a psychopathy checklist (PCL-SV) and cortical thickness. Magnetic resonance imaging (MRI) and surface-based cortical segmentation were used to calculate cortical thickness. Analyses used both regions of interest and statistical maps. When the two groups of offenders were compared, there were no differences in cortical thickness, but the PSY group had thinner cortex in the temporal lobes and in the whole right hemisphere compared to RG. There were no differences in cortical thickness between the ASD group and RG. Across subjects there was a negative correlation between PCL-SV scores and cortical thickness in the temporal lobes and the whole right hemisphere. The findings indicate that thinner cortex in the temporal lobes is present in psychopathic offenders and that these regions are important for the expression of psychopathy. However, whether thinner temporal cortex is a cause or a consequence of the antisocial behaviour is still unknown.
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| 18. |
- Jonsson, Maria, 1966-, et al.
(författare)
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Assessment of pain in women randomly allocated to speculum or digital insertion of the Foley catheter for induction of labor
- 2011
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 90:9, s. 997-1004
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveThe primary aim was to assess pain subjectively and objectively in women during insertion of a Foley catheter for induction of labor. A secondary aim was to assess pain during cervical ripening and to evaluate maternal satisfaction.DesignRandomized controlled trial. Setting. University hospital, Sweden. Population. Forty-two women undergoing induction of labor and cervical ripening with a Foley catheter.MethodsWomen were randomly allocated to digital (n=21) or to speculum (n=21) placement of a Foley catheter. A visual analogue scale (VAS) was used for subjective assessment of pain and, for objective measurements, a skin conductance algesimeter was used and the area under the curve (AUC) was calculated (mu Ss). Maternal satisfaction was evaluated in a questionnaire. Main outcome measures. Pain sensation during placement of the Foley catheter.ResultsThere was a significant difference between groups in pain measurements during insertion of the Foley catheter. The speculum group had higher median pain scores than the digital group, VAS=5 vs. = 3 (p=0.03) and greater median AUC measurements: 1840 vs. 823 mu Ss (p=0.04). There was no difference in pain assessments during cervical ripening. Overall satisfaction scores were high and comparable between groups.ConclusionDigital placement of the Foley catheter is subjectively and objectively less painful compared to the use of a speculum. Digital placement should therefore be considered as an alternative in the management of these patients. Ripening of the cervix with the Foley catheter is well tolerated and the overall satisfaction rate among patients induced with this method is high.
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| 19. |
- Liberg, Benny, et al.
(författare)
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Motor imagery in bipolar depression with slowed movement.
- 2013
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Ingår i: The Journal of nervous and mental disease. - 1539-736X. ; 201:10, s. 885-93
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that motor retardation in bipolar depression is mediated by disruption of the pre-executive stages of motor production. We used functional magnetic resonance imaging to investigate neural activity during motor imagery and motor execution to elucidate whether brain regions that mediate planning, preparation, and control of movement are activated differently in subjects with bipolar depression (n = 9) compared with healthy controls (n = 12). We found significant between-group differences. During motor imagery, the patients activated the posterior medial parietal cortex, the posterior cingulate cortex, the premotor cortex, the prefrontal cortex, and the frontal poles more than the controls did. Activation in the brain areas involved in motor selection, planning, and preparation was altered. In addition, limbic and prefrontal regions associated with self-reference and the default mode network were altered during motor imagery in bipolar depression with motor retardation.
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| 20. |
- Mantovani, Maria Cristina, 1974-
(författare)
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Schwann cells and mesenchymal stem cells as promoter of peripheral nerve regeneration
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The transplantation of primary Schwann cells (SC) has been shown to improve nerve regeneration. However, to monitor the survival of transplanted cells within the host, a stable labelling method is required. The in vitro characteristics of green fluorescent protein labelled SC (GFP SC) and their effects in an in vivo peripheral nerve injury model were investigated. The GFP-SC were readily visualised ex vivo and stimulated significantly better axonal regeneration compared to controls. Clinical use of autologous SC for the treatment of nerve injuries is of limited use due to difficulty in obtaining clinically useful numbers. However, bone marrow mesenchymal stem cells (MSC) can trans-differentiate into SC like cells (dMSC). The in vitro and in vivo differentiation of MSC was explored, and the study extended to include the easily-accessible adipose stem cells (ASC). In vitro, glial growth factor stimulated MSC express S100, a SC marker, and its expression is maintained following in vivo transplantation. Similarly, untreated MSC transplanted in vivo also expressed S100, which indicates glial differentiation in response to local cytokines and growth factors. Using an in vitro model, comprising dMSC or dASC co-cultured with adult dorsal root ganglia (DRG) neurons, the capacity of the dMSC and SC like differentiated ASC (dASC) to promote axon myelination was verified: both cell types expressed transcripts for protein zero, peripheral myelin protein-22 and myelin basic protein.The potential of stem cells in nerve repair may be limited by innate cellular senescence or donor age affecting cell functionality thus it was essential to determine the effects of donor age on morphology and functionality of stem cells. The proliferation rates, expression of senescence markers (p38 and p53) and the stimulation of neurite outgrowth from DRG neurons by stem cells isolated from neonatal, young or old rats were very similar. However, the distribution and ultrastructure of mitochondria in dMSC and dASC from young and old rats were quite different, and seem to indicate physiological senescence of the aged cells. Given the wide-ranging influence of Notch signalling in cell differentiation, including the neural crest to a glial cell type switch, and self-renewal in mammals, its role in the differentiation of stem cells to SC was investigated. The mRNA for notch-1 and -2 receptors were expressed in the dASC, blockage of notch signaling did not affect the neurotrophic and myelination potential of dASC. In conclusion, these findings show that GFP labelling has no deleterious effect on SC survival and function. MSC and ASC differentiated into glial-type cells acquire SC morphology, and express characteristic SC markers, and the differentiation process was independent of the Notch signaling pathway. Also, following transplantation into a nerve gap injury dMSC improve regeneration. This study established that following co-culture with DRG neurons, dMSC and dASC were able to express peripheral myelin proteins. Also, the functional bioactivity of these cells is independent of the donor animal age. Finally, although the glial lineage differentiated aged cells characterized in this study expressed markers typical of senescence they retained the potential to support axon regeneration.
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