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Sökning: WFRF:(Spenger Christian) > (2005-2009)

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  • Bereczky-Veress, Biborka, et al. (författare)
  • Host strain-dependent difference in susceptibility in a rat model of herpes simplex type 1 encephalitis.
  • 2008
  • Ingår i: Journal of neurovirology. - 1538-2443. ; 14:2, s. 102-18
  • Tidskriftsartikel (refereegranskat)abstract
    • Herpes simplex encephalitis (HSE) is characterized by severe focal brain inflammation leading to substantial loss of nervous tissue. The authors established a model of Herpes simplex virus type 1 (HSV)-1-induced acute encephalitis in the rat by injecting into the whiskers' area a virus strain isolated from a fatal human HSE case. The model might resemble natural propagation of HSV-1 in humans; spreading from the mouth and lips via the trigeminal nerve to trigeminal ganglia and subsequently entering the central nervous system (CNS). HSV-1 infected Dark Agouti (DA) rats developed a well-synchronized disease and died 5 days after inoculation. HSV-1 detection by quantitative polymerase chain reaction (qPCR), virus isolation and immunohistochemistry, magnetic resonance imaging, and histopathological examination verified dramatic encephalitis mainly in the brainstem, but also in the olfactory bulb and other segments of the brain of diseased rats. In contrast, Piebald Virol Glaxo (PVG) rats were completely resistant to disease, displaying a more rapid clearance of peripheral infection and no evidence of virus entering into neither the trigeminal ganglia nor the CNS. These results suggest a regulation of susceptibility to HSV-1-induced encephalitis at the level of peripheral infection and subsequent neuronal uptake/transport of the virus. This provides a basis for future positioning of genetic polymorphisms regulating HSE and for dissection of important pathogenetic mechanisms of this severe human disease.
  • Hofstetter, Christoph P, et al. (författare)
  • Allodynia limits the usefulness of intraspinal neural stem cell grafts; directed differentiation improves outcome.
  • 2005
  • Ingår i: Nature Neuroscience. - 1097-6256 .- 1546-1726. ; 8:3, s. 346-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Several studies have reported functional improvement after transplantation of neural stem cells into injured spinal cord. We now provide evidence that grafting of adult neural stem cells into a rat thoracic spinal cord weight-drop injury improves motor recovery but also causes aberrant axonal sprouting associated with allodynia-like hypersensitivity of forepaws. Transduction of neural stem cells with neurogenin-2 before transplantation suppressed astrocytic differentiation of engrafted cells and prevented graft-induced sprouting and allodynia. Transduction with neurogenin-2 also improved the positive effects of engrafted stem cells, including increased amounts of myelin in the injured area, recovery of hindlimb locomotor function and hindlimb sensory responses, as determined by functional magnetic resonance imaging. These findings show that stem cell transplantation into injured spinal cord can cause severe side effects and call for caution in the consideration of clinical trials.
  • Oberg, Johanna, et al. (författare)
  • Age related changes in brain metabolites observed by 1H MRS in APP/PS1 mice
  • 2008
  • Ingår i: Neurobiology of Aging. - 0197-4580 .- 1558-1497. ; 29:9, s. 1423-1433
  • Tidskriftsartikel (refereegranskat)abstract
    • Translational biomarkers in Alzheimer's disease based on non-invasive in vivo methods are highly warranted. (1)H magnetic resonance spectroscopy (MRS) is non-invasive and applicable in vivo in both humans and experimental animals. In vivo(1)H MRS and 3D MRI were performed on brains of double transgenic (tg) mice expressing a double mutant human beta-amyloid precursor protein APP(K670N,M671L) and human mutated presenilin gene PS1M146L, and wild-type (wt) littermates at 2.5, 6.5 and 9 months of age using a 9.4T magnet. For quantification, LCModel was used, and the data were analyzed using multivariate data analysis (MVDA). MVDA evidenced a significant separation, which became more pronounced with age, between tg and wt mice at all time points. While myo-inositol and guanidoacetate were important for group separation in young mice, N-acetylaspartate, glutamate and macrolipids were important for separation of aged tg and wt mice. Volume segmentation revealed that brain and hippocampus were readily smaller in tg as compared to wt mice at the age of 2.5 months. Amyloid plaques were seen in 6.5 and 9 months, but not in 2.5 months old animals. In conclusion, differences in brain metabolites could be accurately depicted in tg and wt mice in vivo by combining MRS with MVDA. First differences in metabolite content were readily seen at 2.5 months, when volume defects in tg mice were present, but no amyloid plaques.
  • Thonabulsombat, Charoensri, et al. (författare)
  • Implanted embryonic sensory neurons project axons toward adult auditory brainstem neurons in roller drum and Stoppini co-cultures
  • 2007
  • Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1170, s. 48-58
  • Tidskriftsartikel (refereegranskat)abstract
    • Previously we have shown in vivo the survival, migration and integration of embryonic dorsal root ganglion (DRG) neurons that were grafted into the inner ear and peripheral auditory nervous system. In order to evaluate relevant factors determining integration of sensory neurons further into the central auditory nervous system, complementary in vitro techniques are necessary. The advantages of in vitro systems are that a large number of factors including various grafts and different conditions can be efficiently examined for. Hence, we co-cultured 300 mu m thick postnatal rat brainstem slices containing the cochlear nucleus including the central part of the 8th cranial nerve with mouse embryonic DRG neurons. The organotypic co-cultures were either grown on coverslips using the roller drum method described by Gahwiler or on membranes according to the interface method described by Stoppini. Neurons in the cochlear nucleus were labeled, with DiI. The results demonstrate that (1) brainstem slices survive for up to 5 weeks in culture, and that (2) co-cultures of embryonic sensory neurons and brainstern show a high degree of neuronal survival, and that (3) survival and axonal outgrowth from the implanted embryonic neurons are dependant on the presence of the brainstern slice rather than on exogenous NGF and that (4) implanted embryonic neurons send axons toward neurons in the cochlear nucleus. (c) 2007 Published by Elsevier B.V.
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