| 1. |
- Trolle, Carl, 1985-
(författare)
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Stem Cell Transplantation in Dorsal Root Injury
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- After traumatic injuries to the brachial plexus there is a risk that one or more of the spinal roots are torn from the spinal cord, known as avulsion injury. This often leads to paralysis and chronic pain, notoriously difficult to treat with current pharmacotherapy. Surgical treatment may improve motor function but sensory recovery is usually poor as sensory axons fail to establish functional connections inside the spinal cord. The aims of this thesis were to develop a model for dorsal root avulsion in rodents in order to investigate the potentials of stem cell therapy for enhancing sensory regeneration after spinal root avulsion. Two different types of stem cells, embryonic and neural crest stem cells, have been transplanted to the avulsion model and analysed using immunohistochemical methods. The results indicate that stem cells survive after transplantation to the avulsed dorsal root and associate with regenerating axons. Furthermore, the different stem cells display different phenotypes after transplantation where embryonic stem cells give rise to neurons located outside the spinal cord that could serve as projection neurons whereas the neural crest stem cells form elongated tubes outlining the avulsed dorsal root and are associated with regenerating neuronal fibers. We have also discovered that the neural crest stem cells migrate into the damaged spinal cord as single cells. The neural crest stem cells also display a diversity in generating both neuronal and glial cells that may have different beneficial effects in neural repair following dorsal root avulsion. To improve the survival of stem cell transplants, the potentials of co-transplanting embryonic stem cells together with nanoparticle delivered growth factor mimetics has been investigated. The results indicate that nanoparticle delivered growth factors improve both transplant survival and maturation in comparison to untreated controls and may be a promising strategy in stem cell transplantation.
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| 2. |
- Ekmark Lewén, Sara, 1978-
(författare)
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Cellular Reactions and Behavioral Changes in Focal and Diffuse Traumatic Brain Injury : A Study in the Rat and Mouse
- 2013
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Traumatic brain injury (TBI) is a severe condition and a major cause of death and disability. There is no pharmacological treatment available in clinical practice today and knowledge of brain injury mechanisms is of importance for development of neuroprotective drugs. The aims of the thesis were to get a better understanding of astrocyte reactions and immune responses, as well as behavioral changes after focal unilateral cortical contusion injury and diffuse bilateral central fluid percussion injury in rats and mice.In the focal injury models, the astrocyte reactions were generally restricted to the ipsilateral hemisphere. After diffuse TBI, vimentin and glial fibrillary acidic protein (GFAP) positive reactive astrocytes were bilaterally expressed in brain regions even distant from the injury site, including regions where axonal injury was seen. Early after diffuse TBI, there was a robust immune response, including activation of macrophages/microglia (Mac-2+) and infiltration of neutrophils (GR-1+) and T-cells (CD3+).In order to measure functional outcome, the recently established Multivariate Concentric Square Field™ (MCSF) test for complex behaviors, including risk taking and explorative strategies was used. The Morris water maze (MWM) was applied for testing learning and memory. The MCSF test revealed alterations in risk taking, risk assessment and exploratory behavior, in the mice subjected to focal injury whereas mice subjected to the diffuse injury showed a deviant stereotyped behavior. After focal injury mice showed a decreased ability to adapt to the arena in the second trial, when tested repeatedly in the MCSF test. Mice subjected to diffuse injury had an impaired memory but not learning, in the MWM test. Post-injury treatment with the anti-inflammatory anti-interleukin-1β (IgG2 a/k) antibody showed a positive effect on functional outcome in the diffuse injury model. Altogether, the results demonstrate that focal and diffuse TBI models produce differences in cellular reactions and behavioral outcome and that the immune response plays a key role in the pathology after brain injury.
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| 3. |
- Jerregård, Helena
(författare)
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Factors influencing nerve growth in situ and in vitro
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Bakgranden till denna doktorsavhaodling är den problematik som uppstår efter en perifer nervskada, roreträdesvis i relation till handen eftersom den har så stor betydelse i vårt dagliga liv. En haod utan känsel fungerar dåligt och än sänne fungerar en handprotes. Problemet idag är inte att få nervtrådarna att växa efter en skada utan att få dem att växa rätt. Dagens mikrokirurgiska behandling av nervskador är mycket förfinad. Vi kan inte vänta oss att en fortsatt utveckling av mikrokirurgin på ett dramatiskt sätt skall bidra till en rorbättring av vår rormåga att leda utväxande nervtrådar till deras mål organ. Därror är det viktigt att studera de molekylära faktorer som bidrar till styrning av nervväxt För att studera detta har jag använt mig av två olika modeller. Först gjorde jag en experimentell studie på vuxen råtta. Frågeställningen var om man med lljälp av filtrat gjorda från två olika målorgan (muskel och hud) kan styra utväxaode nervtrådar att växa åt rätt håll. Detta visade sig vara möjligt, och frågan väcktes då hur samspelet mellao nerv och målorgao såg ut på cellnivå. För att besvara den frågan utvecklade jag en in vitro-modell där jag odlade känselnervceller tillsammans med bindvävsceller från huden (känselcellemas målorgan). Jag har använt denna odlingsmodell i tre arbeten ror att undersöka hur vissa kända molekyler påverkar nervväxt. I ett arbete beskriver jag effekter av lösta molekyler (neurotrofiner) på nervväxt I ett annat arbete studeras betydelsen av molekyler som är bundna till cellytor (celladhesionsmolekyler) för nervväxt. En tredje studie rör effekter av ämnen som flisätts vid inflammation (cytokiner) på nervväxt. Sammanfattningsvis har denna avhaodling bidragit till att öka vår kunskap om olika faktorer som är viktiga för nervväxt I en framtid kommer vi förhoppningsvis attkunna sätta ihop all den konskap om nervväxt som just nu ackumul eras på olika håll i världen till en aovändbar helhet och tillämpa den vid behaodlingen av perifera nervskador.
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| 4. |
- Karlsson, Magnus
(författare)
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Ganglionic nerve fibres in ventral roots
- 1995
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- According to the law of Magendie, the ventral roots channel efferent nerve fibres from the spinal cord to the periphery, while the dorsal roots channel afferent axons from the periphery into the spinal cord. However, as sensory C-fibres have been observed in mammalian ventral roots outside the autonomic outflow, this law has been questioned. On the basis of other observations, though, ganglionic axons have been suggested not to enter the spinal cord via ventral roots. This thesis presents data on the occurrence of C-fibres in simian ventral roots and provides some new aspects on the occurrence, configuration and function of putative ganglionic ventral root axons in the rat.Paper I shows that putative ganglionic C-fibres occur in the primate ventral root L7, which is outside the autonomic outflow. Like in the cat, these axons do not seem to enter the spinal cord via this root. The ventral root SI does also contain C-fibres, but it seems that these fibres are preganglionic autonomic axons. Some putative ganglionic fibres are also present in the lumbosacral spinal pia mater. Hence, these results conform with the law of Magendie. Paper II shows that putative afferent axons in the rat ventral roots L4-S 1 take a longitudinal course, make zig-zag deviations, loop, branch, end blindly or shift to the spinal pia mater. No putative afferent axons enter the spinal cord via ventral roots. These results agree with the law of Magendie. The results of Paper III suggest that sensory and sympathetic ganglionic axons grow into the rat ventral roots L4-L5 and corresponding pia mater during postnatal development. The afferent axons course as decribed in Paper II. The postganglionic sympathetic axons sometimes loop, but most of them enter the pia mater where they usually associate with blood vessels. A few putative sympathetic fibres enter the spinal cord via ventral roots. Some extra postganglionic sympathetic fibres may enter ventral roots during aging. Paper IV shows that putative afferent rat ventral root axons arecapsaicin-resistant and that they fail to evoke plasma protein extravasation in the root and pia mater. In this respect, they differ from similar axons at many other peripheral locations. The results of Paper V show that C-fibres invade the rat ventral root L5 after neonatal, but not adult, sciatic nerve crush. The extra axons do not seem to represent afferents. At least some proportion of these axons seem to represent putative postganglionic sympathetic axons.
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