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Aldskogius, Håkan
Alternative names
Publications (10 of 41) Show all publications
Hoeber, J., König, N., Trolle, C., Lekholm, E., Zhou, C., Pankratova, S., . . . Kozlova, E. (2017). A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord. Stem Cells and Development, 26(14), 1065-1077
Open this publication in new window or tab >>A Combinatorial Approach to Induce Sensory Axon Regeneration into the Dorsal Root Avulsed Spinal Cord
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2017 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 26, no 14, p. 1065-1077Article in journal (Refereed) Published
Abstract [en]

Spinal root injuries result in newly formed glial scar formation, which prevents regeneration of sensory axons causing permanent sensory loss. Previous studies showed that delivery of trophic factors or implantation of human neural progenitor cells supports sensory axon regeneration and partly restores sensory functions. In this study, we elucidate mechanisms underlying stem cell-mediated ingrowth of sensory axons after dorsal root avulsion (DRA). We show that human spinal cord neural stem/progenitor cells (hscNSPC), and also, mesoporous silica particles loaded with growth factor mimetics (MesoMIM), supported sensory axon regeneration. However, when hscNSPC and MesoMIM were combined, sensory axon regeneration failed. Morphological and tracing analysis showed that sensory axons grow through the newly established glial scar along "bridges" formed by migrating stem cells. Coimplantation of MesoMIM prevented stem cell migration, "bridges" were not formed, and sensory axons failed to enter the spinal cord. MesoMIM applied alone supported sensory axons ingrowth, but without affecting glial scar formation. In vitro, the presence of MesoMIM significantly impaired migration of hscNSPC without affecting their level of differentiation. Our data show that (1) the ability of stem cells to migrate into the spinal cord and organize cellular "bridges" in the newly formed interface is crucial for successful sensory axon regeneration, (2) trophic factor mimetics delivered by mesoporous silica may be a convenient alternative way to induce sensory axon regeneration, and (3) a combinatorial approach of individually beneficial components is not necessarily additive, but can be counterproductive for axonal growth.

Keywords
biomimetics, neural stem cells, spinal cord regeneration, stem cell transplantation
National Category
Neurosciences Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Hematology
Identifiers
urn:nbn:se:uu:diva-328587 (URN)10.1089/scd.2017.0019 (DOI)000405071200005 ()28562227 (PubMedID)
Funder
Stiftelsen Olle Engkvist ByggmästareSwedish Research Council, 20716
Note

De två första författarna delar förstaförfattarskapet.

Available from: 2017-08-28 Created: 2017-08-28 Last updated: 2018-01-13Bibliographically approved
König, N., Trolle, C., Kapuralin, K., Adameyko, I., Mitrecic, D., Aldskogius, H., . . . Kozlova, E. (2017). Murine neural crest stem cells and embryonic stem cell derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion. Journal of Tissue Engineering and Regenerative Medicine, 11(1), 129-137
Open this publication in new window or tab >>Murine neural crest stem cells and embryonic stem cell derived neuron precursors survive and differentiate after transplantation in a model of dorsal root avulsion
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2017 (English)In: Journal of Tissue Engineering and Regenerative Medicine, ISSN 1932-6254, E-ISSN 1932-7005, Vol. 11, no 1, p. 129-137Article in journal (Refereed) Published
Abstract [en]

Spinal root avulsion results in paralysis and sensory loss, and is commonly associated with chronic pain. In addition to the failure of avulsed dorsal root axons to regenerate into the spinal cord, avulsion injury leads to extensive neuroinflammation and degeneration of second order neurons in the dorsal horn. The ultimate objective with the treatment of this condition is to counteract degeneration of spinal cord neurons and to achieve functionally useful regeneration/reconnection of sensory neurons with spinal cord neurons. Here we explore if stem cells transplanted on the surface of avulsed spinal cord can survive, differentiate and migrate into the damaged spinal cord during the first few weeks after this intervention. Murine boundary cap neural crest stem cells (bNCSCs) or embryonic stem cell (ESC)-derived, pre-differentiated neuron precursors were implanted acutely at the junction between avulsed dorsal roots L3-L6 and the spinal cord. Both types of cells survived transplantation, but showed distinctly different modes of differentiation. Thus, bNCSCs migrated into the spinal cord, expressed glial markers, and formed elongated tubes in the peripheral nervous system (PNS) compartment of the avulsed dorsal root transitional zone(DRTZ) area. In contrast, the ESC-transplants remained at the site of implantation and differentiated to motor neurons and interneurons. These data show that both stem cell types successfully survive implantation to the acutely injured spinal cord and maintained their differentiation and migration potential. These data suggest that depending on the source of neural stem cells, they can play different beneficial roles for recovery after dorsal root avulsion.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
sensory neuron, spinal cord, dorsal root transitional zone, regeneration, migration, glial cells, Schwann cells, motor neurons
National Category
Neurosciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-218684 (URN)10.1002/term.1893 (DOI)000394173600012 ()24753366 (PubMedID)
Funder
Swedish Research Council, 20716
Available from: 2014-02-14 Created: 2014-02-14 Last updated: 2018-01-11Bibliographically approved
Latini, F., Mårtensson, J., Larsson, E.-M., Fredriksson, M., Åhs, F., Hjortberg, M., . . . Ryttlefors, M. (2017). Segmentation of the inferior longitudinal fasciculus in the human brain: A white matter dissection and diffusion tensor tractography study.. Brain Research (1675), 102-115, Article ID S0006-8993(17)30386-4.
Open this publication in new window or tab >>Segmentation of the inferior longitudinal fasciculus in the human brain: A white matter dissection and diffusion tensor tractography study.
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2017 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, no 1675, p. 102-115, article id S0006-8993(17)30386-4Article in journal (Refereed) Published
Abstract [en]

The inferior longitudinal fascicle (ILF) is one of the major occipital-temporal association pathways. Several studies have mapped its hierarchical segmentation to specific functions. There is, however, no consensus regarding a detailed description of ILF fibre organisation. The aim of this study was to establish whether the ILF has a constant number of subcomponents. A secondary aim was to determine the quantitative diffusion proprieties of each subcomponent and assess their anatomical trajectories and connectivity patterns. A white matter dissection of 14 post-mortem normal human hemispheres was conducted to define the course of the ILF and its subcomponents. These anatomical results were then investigated in 24 right-handed, healthy volunteers using in vivo diffusion tensor imaging (DTI) and streamline tractography. Fractional anisotropy (FA), volume, fibre length and the symmetry coefficient of each fibre group were analysed. In order to show the connectivity pattern of the ILF, we also conducted an analysis of the cortical terminations of each segment. We confirmed that the main structure of the ILF is composed of three constant components reflecting the occipital terminations: the fusiform, the lingual and the dorsolateral-occipital. ILF volume was significantly lateralised to the right. The examined indices of ILF subcomponents did not show any significant difference in lateralisation. The connectivity pattern and the quantitative distribution of ILF subcomponents suggest a pivotal role for this bundle in integrating information from highly specialised modular visual areas with activity in anterior temporal territory, which has been previously shown to be important for memory and emotions.

Keywords
DTT, ILF, Occipital-temporal connectivity, Social cognition, Visual memory, White matter
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-329751 (URN)10.1016/j.brainres.2017.09.005 (DOI)000413608600011 ()28899757 (PubMedID)
Available from: 2017-09-20 Created: 2017-09-20 Last updated: 2018-02-02Bibliographically approved
Hoeber, J., Trolle, C., König, N., Du, Z., Gallo, A., Hermans, E., . . . Kozlova, E. N. (2015). Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury. Scientific Reports, 5, Article ID 10666.
Open this publication in new window or tab >>Human Embryonic Stem Cell-Derived Progenitors Assist Functional Sensory Axon Regeneration after Dorsal Root Avulsion Injury
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 10666Article in journal (Refereed) Published
Abstract [en]

Dorsal root avulsion results in permanent impairment of sensory functions due to disconnection between the peripheral and central nervous system. Improved strategies are therefore needed to reconnect injured sensory neurons with their spinal cord targets in order to achieve functional repair after brachial and lumbosacral plexus avulsion injuries. Here, we show that sensory functions can be restored in the adult mouse if avulsed sensory fibers are bridged with the spinal cord by human neural progenitor (hNP) transplants. Responses to peripheral mechanical sensory stimulation were significantly improved in transplanted animals. Transganglionic tracing showed host sensory axons only in the spinal cord dorsal horn of treated animals. Immunohistochemical analysis confirmed that sensory fibers had grown through the bridge and showed robust survival and differentiation of the transplants. Section of the repaired dorsal roots distal to the transplant completely abolished the behavioral improvement. This demonstrates that hNP transplants promote recovery of sensorimotor functions after dorsal root avulsion, and that these effects are mediated by spinal ingrowth of host sensory axons. These results provide a rationale for the development of novel stem cell-based strategies for functionally useful bridging of the peripheral and central nervous system.

National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-251488 (URN)10.1038/srep10666 (DOI)000356063500001 ()26053681 (PubMedID)
Funder
Swedish Research Council, 5420, 20716
Available from: 2015-04-20 Created: 2015-04-20 Last updated: 2018-01-11Bibliographically approved
Latini, F., Hjortberg, M., Aldskogius, H. & Ryttlefors, M. (2015). The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection. Behavioural Neurology, Article ID 872645.
Open this publication in new window or tab >>The Classical Pathways of Occipital Lobe Epileptic Propagation Revised in the Light of White Matter Dissection
2015 (English)In: Behavioural Neurology, ISSN 0953-4180, E-ISSN 1875-8584, article id 872645Article in journal (Refereed) Published
Abstract [en]

The clinical evidences of variable epileptic propagation in occipital lobe epilepsy (OLE) have been demonstrated by several studies. However the exact localization of the epileptic focus sometimes represents a problem because of the rapid propagation to frontal, parietal, or temporal regions. Each white matter pathway close to the supposed initial focus can lead the propagation towards a specific direction, explaining the variable semiology of these rare epilepsy syndromes. Some new insights in occipital white matter anatomy are herein described by means of white matter dissection and compared to the classical epileptic patterns, mostly based on the central position of the primary visual cortex. The dissections showed a complex white matter architecture composed by vertical and longitudinal bundles, which are closely interconnected and segregated and are able to support specific high order functions with parallel bidirectional propagation of the electric signal. The same sublobar lesions may hyperactivate different white matter bundles reemphasizing the importance of the ictal semiology as a specific clinical demonstration of the subcortical networks recruited. Merging semiology, white matter anatomy, and electrophysiology may lead us to a better understanding of these complex syndromes and tailored therapeutic options based on individual white matter connectivity.

National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-255314 (URN)10.1155/2015/872645 (DOI)000354304900001 ()
Available from: 2015-06-16 Created: 2015-06-15 Last updated: 2017-12-04Bibliographically approved
Latini, F., Hjortberg, M., Aldskogius, H. & Ryttlefors, M. (2015). The use of a cerebral perfusion and immersion-fixation process for subsequent white matter dissection. Journal of Neuroscience Methods, 253, 161-169
Open this publication in new window or tab >>The use of a cerebral perfusion and immersion-fixation process for subsequent white matter dissection
2015 (English)In: Journal of Neuroscience Methods, ISSN 0165-0270, E-ISSN 1872-678X, Vol. 253, p. 161-169Article in journal (Refereed) Published
Abstract [en]

Background: The Klingler's method for white matter dissection revolutionized the study of deep cerebral anatomy. Although this technique made white matter dissection more feasible and widely used, it still presents some intrinsic limitations. New method: We evaluated the quality of different methods for specimen preparation based on an intra-carotidal formalin perfusion fixation process. Ten post-mortem human hemispheres were prepared with this method and dissected in a stepwise manner. Results: The homogeneous and rapid fixation of the brain allowed documentation of several fine additional anatomical details. Intra-cortical white matter terminations were described during the first stage of dissection on each specimen. No limitations were encountered during dissection of the major associative bundles. On the contrary, the quality of the fixation of the specimens made it possible to isolate them en bloc. One of the most complex and deep bundles (accumbo-frontal fasciculus) was dissected without technical limitations. Deep vascular structures were very well preserved and dissected within the white matter until their sub-millimetric terminations. Comparison with existing method: Short time for preparation, a more homogeneous fixation, no technical limitation for a detailed description of superficial and deep white matter anatomy, the possibility to dissect with a single technique the fibre organization and the white matter vascular architecture are the advantages reported with the perfusion fixation. Conclusion: These results provide encouraging data about the possibility to use a perfusion fixation process, which may help in improving the quality of white matter dissection for research, didactic purposes and surgical training.

Keywords
Fibre dissection, White matter, Klingler, Fixation, Perfusion, Deep vascular anatomy, Accumbo-frontal fasciculus
National Category
Neurosciences
Identifiers
urn:nbn:se:uu:diva-263428 (URN)10.1016/j.jneumeth.2015.06.019 (DOI)000360867400017 ()26149289 (PubMedID)
Available from: 2015-10-12 Created: 2015-09-30 Last updated: 2018-01-11
Garcia-Bennett, A. E., Kozhevnikova, M., König, N., Zhou, C., Leao, R., Knöpfel, T., . . . Kozlova, E. N. (2013). Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells. Stem Cells Translational Medicine, 2(11), 906-915
Open this publication in new window or tab >>Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells
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2013 (English)In: Stem Cells Translational Medicine, ISSN 2157-6564, E-ISSN 2157-6580, Vol. 2, no 11, p. 906-915Article in journal (Refereed) Published
Abstract [en]

Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation.

Keywords
Cell transplantation, Differentiation, Embryonic stem cells, Nervous system, Neural differentiation, Neural stem cell, Stem cell culture, Transplantation
National Category
Natural Sciences Engineering and Technology
Research subject
Engineering Science with specialization in Nanotechnology and Functional Materials
Identifiers
urn:nbn:se:uu:diva-211443 (URN)10.5966/sctm.2013-0072 (DOI)000326312000017 ()
Note

De 3 första författarna delar förstaförfattarskapet

Available from: 2013-11-27 Created: 2013-11-25 Last updated: 2017-12-06Bibliographically approved
Aldskogius, H. & Kozlova, E. N. (2013). Microglia and Neuropathic Pain. CNS & Neurological Disorders: Drug Targets, 12(6), 768-772
Open this publication in new window or tab >>Microglia and Neuropathic Pain
2013 (English)In: CNS & Neurological Disorders: Drug Targets, ISSN 1871-5273, E-ISSN 1996-3181, Vol. 12, no 6, p. 768-772Article in journal (Refereed) Published
Abstract [en]

Neuropathic pain is a serious consequence of injury or disease in the nervous system itself. Current treatment options for this condition are often unsatisfactory. From being originally viewed as a diseased caused by neuronal dysfunction, a growing body of evidence implicate activated microglia as a key player in the development of this pain condition. In this review, some of the evidence for this proposal is briefly discussed and placed in a translational context, pointing out the difficulties in translating commonly used animal models of neuropathic pain to the clinical condition, as well as emphasizing the broader role of activated microglia in the injured or diseased nervous system.

Keywords
Nerve injury, spinal cord injury, neuropathy, cytokine, chemokine, purine receptor, plasticity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-214056 (URN)10.1002/glia.20871 (DOI)000327797200009 ()24047529 (PubMedID)
Available from: 2014-01-07 Created: 2014-01-07 Last updated: 2017-12-06Bibliographically approved
Aldskogius, H. (Ed.). (2012). Animal models of spinal cord repair. New York Heidelberg Dordrecht London: Humana Press
Open this publication in new window or tab >>Animal models of spinal cord repair
2012 (English)Collection (editor) (Other academic)
Place, publisher, year, edition, pages
New York Heidelberg Dordrecht London: Humana Press, 2012. p. 335
Series
Springer Protocols Neuromethods, ISSN 0893-2336 ; 76
Keywords
Spinal cord injury, Anatomy, Physiology, Nerve degeneration, Nerve regeneration, Glial cells, Vascular system, Behavior, Pharmacology, Cell therapy, Imaging, Translation
National Category
Neurosciences
Research subject
Neurology
Identifiers
urn:nbn:se:uu:diva-274230 (URN)10.1007/978-1-62703-197-4 (DOI)978-1-62703-196-7 (ISBN)
Available from: 2016-01-20 Created: 2016-01-20 Last updated: 2018-01-10Bibliographically approved
König, N., Åkesson, E., Telorack, M., Vasylovska, S., Ngamjariyawat, A., Sundström, E., . . . Kozlova, E. N. (2011). Forced Runx1 expression in human neural stem/progenitor cells transplanted to the rat dorsal root ganglion cavity results in extensive axonal growth specifically from spinal cord-derived neurospheres. Stem Cells and Development, 20(11), 1847-1857
Open this publication in new window or tab >>Forced Runx1 expression in human neural stem/progenitor cells transplanted to the rat dorsal root ganglion cavity results in extensive axonal growth specifically from spinal cord-derived neurospheres
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2011 (English)In: Stem Cells and Development, ISSN 1547-3287, E-ISSN 1557-8534, Vol. 20, no 11, p. 1847-1857Article in journal (Refereed) Published
Abstract [en]

Cell replacement therapy holds great promise for treating a wide range of human disorders. However, ensuring the predictable differentiation of transplanted stem cells, eliminating their risk of tumor formation, and generating fully functional cells after transplantation remain major challenges in regenerative medicine. Here, we explore the potential of human neural stem/progenitor cells isolated from the embryonic forebrain (hfNSPCs) or the spinal cord (hscNSPCs) to differentiate to projection neurons when transplanted into the dorsal root ganglion cavity of adult recipient rats. To stimulate axonal growth, we transfected hfNSPC- and hscNSPC-derived neurospheres, prior to their transplantation, with a Tet-Off Runx1-overexpressing plasmid to maintain Runx1 expression in vivo after transplantation. Although pronounced cell differentiation was found in the Runx1-expressing transplants from both cell sources, we observed extensive, long-distance growth of axons exclusively from hscNSPC-derived transplants. These axons ultimately reached the dorsal root transitional zone, the boundary separating peripheral and central nervous systems. Our data show that hscNSPCs have the potential to differentiate to projection neurons with long-distance axonal outgrowth and that Runx1 overexpression is a useful approach to induce such outgrowth in specific sources of NSPCs.

National Category
Medical and Health Sciences
Research subject
Neuroscience
Identifiers
urn:nbn:se:uu:diva-161344 (URN)10.1089/scd.2010.0555 (DOI)000296587400003 ()21322790 (PubMedID)
Note

De 2 första författarna delar förstaförfattarskapet.

Available from: 2011-11-11 Created: 2011-11-11 Last updated: 2017-12-08
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