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Hildebrand, Claes
Publications (10 of 28) Show all publications
Hildebrand, C. & Mohseni, S. (2005). The structure of myelinated axons in the CNS (1ed.). In: Stephen Waxman (Ed.), Multiple Sclerosis As A Neuronal Disease: (pp. 1-28). New York: Elsevier Academic Press
Open this publication in new window or tab >>The structure of myelinated axons in the CNS
2005 (English)In: Multiple Sclerosis As A Neuronal Disease / [ed] Stephen Waxman, New York: Elsevier Academic Press , 2005, 1, p. 1-28Chapter in book (Other academic)
Abstract [en]

This book examines the role of neurons in multiple sclerosis (MS) and the changes that occur in neurons as a result of MS. It places MS in a new and important perspective that not only explains the basis for symptom production, remission, and progress in MS, but also promises to open up new therapeutic possibilities. * Brings together the latest information from clinical, pathological, imaging, molecular, and pharmacological realms to explore the neurobiology of Multiple Sclerosis* Places MS in a new and important perspective that promises to open up new therapeutic avenues* Superbly illustrated and referenced

Place, publisher, year, edition, pages
New York: Elsevier Academic Press, 2005 Edition: 1
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-57236 (URN)0-12-738761-7 (ISBN)978-0-1273-8761-1 (ISBN)
Available from: 2010-06-14 Created: 2010-06-14 Last updated: 2016-02-29Bibliographically approved
Edoff, K. & Hildebrand, C. (2003). Neuropeptide effects on rat chondrocytes and perichondrial cells in vitro. Neuropeptides, 37(5), 316-318
Open this publication in new window or tab >>Neuropeptide effects on rat chondrocytes and perichondrial cells in vitro
2003 (English)In: Neuropeptides, ISSN 0143-4179, E-ISSN 1532-2785, Vol. 37, no 5, p. 316-318Article in journal (Refereed) Published
Abstract [en]

This study examines if cultured chondrocytes and perichondrial cells change the level of cAMP and/or cGMP in response to application of the neuropeptide calcitonin gene-related peptide (CGRP). Cells collected from the knee region of 4–8 days old rat pups were cultured in vitro. Cultures were exposed to 10−10–10−6 M CGRP during 10 minutes. The levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) in the cultures and in controls were determined by radioimmunoassay. The results show that application of CGRP causes a distinctly increased level of cAMP, that was absent when CGRP was applied together with the CGRP1 receptor antagonist. The level of cGMP was not obviously altered. Hence, it is possible that terminals of primary sensory neurones present in developing cartilage influence chondrocytes and perichondrial cells via local release of CGRP.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24997 (URN)10.1016/j.npep.2003.09.001 (DOI)9417 (Local ID)9417 (Archive number)9417 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Lillesaar, C., Arenas, E., Hildebrand, C. & Fried, K. (2003). Responses of rat trigeminal neurones to dental pulp cells or fibroblasts overexpressing neurotrophic factors in vitro. Neuroscience, 119(2), 443-451
Open this publication in new window or tab >>Responses of rat trigeminal neurones to dental pulp cells or fibroblasts overexpressing neurotrophic factors in vitro
2003 (English)In: Neuroscience, ISSN 0306-4522, E-ISSN 1873-7544, Vol. 119, no 2, p. 443-451Article in journal (Refereed) Published
Abstract [en]

The adult dental pulp is innervated by sensory trigeminal axons and efferent sympathetic axons. Rat trigeminal ganglia extend neurites when co-cultivated in vitro with pulpal tissue explants, suggesting that pulpal cells secrete soluble molecules that stimulate the growth of trigeminal ganglion axons. In addition, cultured pulpal cells produce mRNAs for neurotrophins and glial cell line-derived neurotrophic factor-family members. These data suggest that neurotrophic factors are involved in the formation of a pulpal innervation. Here, we examine how pulpal cells and 3T3 fibroblasts overexpressing certain neurotrophic factors (nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, glial cell line-derived neurotrophic factor or neurturin) influence survival and growth of single trigeminal ganglion neurones in vitro in quantitative terms. The results show that most of the neurotrophic factor-overexpressing fibroblasts induce similar neuronal soma diameters, but higher survival rates and neurite lengths compared with pulpal cells. With respect to neurite growth pattern, trigeminal ganglion neurones co-cultured with fibroblasts overexpressing nerve growth factor develop a geometry that is most similar to that seen in co-cultures with pulpal cells. We conclude that none of the fibroblasts overexpressing neurotrophic factors can fully mimic the effects of pulpal cells on trigeminal ganglion neurones, and that nerve growth factor promotes a neurite growth pattern most similar to the picture seen in co-cultures with pulpal cells.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25081 (URN)10.1016/S0306-4522(02)00938-7 (DOI)9511 (Local ID)9511 (Archive number)9511 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Jergovic, D., Stål, P., Lidman, D., Lindvall, B. & Hildebrand, C. (2001). Changes in a rat facial muscle after facial nerve injury and repair. Muscle and Nerve, 24(9), 1202-1212
Open this publication in new window or tab >>Changes in a rat facial muscle after facial nerve injury and repair
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2001 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 24, no 9, p. 1202-1212Article in journal (Refereed) Published
Abstract [en]

This study describes changes in a rat facial muscle innervated by the mandibular and buccal facial nerve branches 4 months after nerve injury and repair. The following groups were studied: (A) normal controls; (B) spontaneous reinnervation by collateral or terminal sprouting; (C) reinnervation after surgical repair of the mandibular branch; and (D) chronic denervation. The normal muscle contained 1200 exclusively fast fibers, mainly myosin heavy chain (MyHC) IIB fibers. In group B, fiber number and fiber type proportions were normal. In group C, fiber number was subnormal. Diameters and proportions of MyHC IIA and hybrid fibers were above normal. The proportion of MyHC IIB fibers was subnormal. Immediate and delayed repair gave similar results with respect to the parameters examined. Group D rats underwent severe atrophic and degenerative changes. Hybrid fibers prevailed. These data suggest that spontaneous regeneration of the rat facial nerve is superior to regeneration after surgical repair and that immediacy does not give better results than moderate delay with respect to surgical repair. Long delays are shown to be detrimental.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25077 (URN)10.1002/mus.1133 (DOI)9507 (Local ID)9507 (Archive number)9507 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Jerregård, H., Åkerud, P., Arenas, E. & Hildebrand, C. (2001). Fibroblast-like cells from rat plantar skin and neurotrophin-transfected 3T3 fibroblasts influence neurite growth from rat sensory neurons in vitro. Journal of Neurocytology, 29(9), 653-663
Open this publication in new window or tab >>Fibroblast-like cells from rat plantar skin and neurotrophin-transfected 3T3 fibroblasts influence neurite growth from rat sensory neurons in vitro
2001 (English)In: Journal of Neurocytology, ISSN 0300-4864, E-ISSN 1573-7381, Vol. 29, no 9, p. 653-663Article in journal (Refereed) Published
Abstract [en]

Our previous finding that skin-derived and muscle-derived molecules can be used to sort regenerating rat sciatic nerve axons evoked questions concerning neuron-target interactions at the level of single cells, which prompted the present study. The results show that dorsal root ganglion (DRG) neurons co-cultured with fibroblast-like skin-derived cells emit many neurites. These have a proximal linear segment and a distal network of beaded branches in direct relation to skin-derived cells. Electron microscopic examination of such co-cultures showed bundles of neurites at some distance from the target cells and single profiles closely apposed to subjacent cells. RNase protection assay revealed that cultivated skin-derived cells express nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and neurotrophin-4 (NT-4). In co-cultures of DRG neurons and 3T3 fibroblasts overexpressing either of the neurotrophins produced by skin-derived cells the picture varied. NT-3 transfected 3T3 fibroblasts gave a growth pattern similar to that seen with skin-derived cells. Neurons co-cultured with mock-transfected 3T3 fibroblasts were small and showed weak neurite growth. In co-cultures with a membrane insert between skin-derived cells or 3T3 fibroblasts and DRG neurons few neurons survived and neurite growth was very sparse. We conclude that skin-derived cells stimulate neurite growth from sensory neurons in vitro, that these cells produce NGF, BDNF, NT-3 and NT-4 and that 3T3 fibroblasts producing NT-3 mimic the effect of skin-derived cells on sensory neurons in co-culture. Finally the results suggest that cell surface molecules are important for neuritogenesis.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25082 (URN)10.1023/A:1010883320683 (DOI)9512 (Local ID)9512 (Archive number)9512 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Jerregård, H., Nyberg, T. & Hildebrand, C. (2001). Sorting of Regenerating Rat Sciatic Nerve Fibers with Target-Derived Molecules. Experimental Neurology, 169(2), 298-306
Open this publication in new window or tab >>Sorting of Regenerating Rat Sciatic Nerve Fibers with Target-Derived Molecules
2001 (English)In: Experimental Neurology, ISSN 0014-4886, E-ISSN 1090-2430, Vol. 169, no 2, p. 298-306Article in journal (Refereed) Published
Abstract [en]

The functional outcome of microsurgical repair of divided nerves is disappointing since many regenerating axons fail to reach appropriate targets. Sorting of regenerating axons according to target tissue might be used to improve functional regeneration. The aim of the present study is to see if regenerating axons can be sorted into functionally different bundles with target-derived molecules. The proximal stump of the adult rat sciatic nerve was sutured into the inlet of a silicon Y-tube. The two branches of the Y-tube were filled with agarose primed with filtrates prepared from skin and muscle homogenates from the operated rat. The tibial and sural nerves were inserted in the two branches of the Y-tube. Six weeks later the sciatic nerve axons showed vigorous regeneration into both branches. Electron microscopic examination of regenerated nerve segments showed numerous myelinated and unmyelinated axons. The proportion of myelinated axons was significantly larger in the muscle-gel branch than in the skin-gel branch. Retrograde tracing from the nerve regenerates with Fast Blue and Fluoro-Ruby showed that ventral horn neurons at L4–L5 segmental levels were preferentially labeled from the muscle-gel branch. Neurons in corresponding dorsal root ganglia were labeled from both Y-tube branches (no significant numerical difference). A few neurons of both types contained both tracers. Measurements revealed that sensory neurons labeled from the muscle-gel branch were significantly larger (mean perikaryal area 870 μm2) than neurons labeled from the skin-gel branch (mean area 580 μm2). We conclude that regenerating motor and sensory axons can be sorted with target-derived molecules.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25080 (URN)10.1006/exnr.2001.7656 (DOI)9510 (Local ID)9510 (Archive number)9510 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Jerregard, H., Akerud, P., Arenas, E. & Hildebrand, C. (2000). Behaviour of rat dorsal root ganglion neurones cocultured in vitro with foot skin fibroblasts or neurotrophin-transfected 3T3-cells. European Journal of Neuroscience, 12
Open this publication in new window or tab >>Behaviour of rat dorsal root ganglion neurones cocultured in vitro with foot skin fibroblasts or neurotrophin-transfected 3T3-cells
2000 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 12, p. 330-330Conference paper, Published paper (Other academic)
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-49522 (URN)
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-12
Anderson, E. S., Bjartmar, C., Eriksson, C., Westermark, G. & Hildebrand, C. (2000). Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro. Neuroscience Letters, 284(1-2), 21-24
Open this publication in new window or tab >>Developing chicken oligodendrocytes express the type IV oligodendrocyte marker T4-O in situ, but not in vitro
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2000 (English)In: Neuroscience Letters, ISSN 0304-3940, E-ISSN 1872-7972, Vol. 284, no 1-2, p. 21-24Article in journal (Refereed) Published
Abstract [en]

Accumulating data suggest that the oligodendrocyte population includes morphological and biochemical subtypes. We recently reported that a polyclonal antiserum against an unknown antigen, the T4-O molecule, labels a subpopulation of chicken oligodendrocytes, obviously representing the type IV variety of Del Rio Hortega. The present study examines the developmental expression of the T4-O molecule in situ and in vitro. The results show that T4-O immunoreactive cells first appear at E15 in the ventral funiculus. But, oligodendrocytes cultured in vitro with or without neurones do not develop a T4-O immunoreactivity. We conclude that oligodendrocytes in the spinal cord of chicken embryos first express the T4-O molecule some time after onset of myelination, and that the T4-O immunoreactive phenotype does not develop in vitro.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24853 (URN)10.1016/S0304-3940(00)00989-7 (DOI)9253 (Local ID)9253 (Archive number)9253 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Mohseni, S., Lillesaar, C., Theodorsson, E. & Hildebrand, C. (2000). Hypoglycaemic neuropathy: Occurrence of axon terminals in plantar skin and plantar muscle of diabetic BB/Wor rats treated with insulin implants. Acta Neuropathologica, 99(3), 257-262
Open this publication in new window or tab >>Hypoglycaemic neuropathy: Occurrence of axon terminals in plantar skin and plantar muscle of diabetic BB/Wor rats treated with insulin implants
2000 (English)In: Acta Neuropathologica, ISSN 0001-6322, E-ISSN 1432-0533, Vol. 99, no 3, p. 257-262Article in journal (Refereed) Published
Abstract [en]

It is generally believed that diabetic neuropathy is due to chronic hyperglycaemia. However, experience from insulinoma patients and experimental studies show that hypoglycaemia may also cause neuropathy. Accordingly, the plantar nerves of diabetic eu-/hypoglycaemic BB/Wor rats treated with insulin implants exhibit a distinct neuropathy. To what extent hypoglycaemic neuropathy affects axon terminals in skin and muscle is unknown. In the present study we examine the occurrence of epidermal axon profiles and the neuropeptide calcitonin gene-related peptide (CGRP) in plantar skin, and of end plate axon terminals in a plantar muscle of diabetic BB/Wor rats subjected to long periods of hypoglycaemia. The number of protein gene product-immunoreactive axon profiles was found to be normal in heel skin biopsy specimens from eu-/hypoglycaemic rats, but many profiles were short and thin. The content of CGRP in the skin biopsy samples was significantly below normal. After staining with antibodies against the vesicular acetylcholine transporter protein, the occurrence of end plate axon terminals was significantly reduced in sections from the flexor hallucis brevis muscle of eu-/hypoglycaemic rats. Moreover, the end plate axon terminals tended to be abnormally small in these rats. We conclude that the hypoglycaemic neuropathy seen in plantar nerve trunks of diabetic BB/Wor rats treated with insulin implants is accompanied by mild alterations in the epidermal innervation of plantar skin and a more obviously abnormal nerve terminal pattern in plantar muscle.

Keywords
Hypoglycaemia, Glabrous skin, Nerve fibre, Plantar muscle, Motor end plate
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25083 (URN)10.1007/PL00007435 (DOI)9513 (Local ID)9513 (Archive number)9513 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
Fried, K., Nosrat, C., Lillesaar, C. & Hildebrand, C. (2000). Molecular signaling and pulpal nerve development. Critical Reviews in Oral Biology and Medicine, 11(3), 318-332
Open this publication in new window or tab >>Molecular signaling and pulpal nerve development
2000 (English)In: Critical Reviews in Oral Biology and Medicine, ISSN 1045-4411, E-ISSN 1544-1113, Vol. 11, no 3, p. 318-332Article in journal (Refereed) Published
Abstract [en]

The purpose of this review is to discuss molecular factors influencing nerve growth to teeth. The establishment of a sensory pulpal innervation occurs concurrently with tooth development. Epithelial/mesenchymal interactions initiate the tooth primordium and change it into a complex organ. The initial events seem to be controlled by the epithelium, and subsequently, the mesenchyme acquires odontogenic properties. As yet, no single initiating epithelial or mesenchymal factor has been identified. Axons reach the jaws before tooth formation and form terminals near odontogenic sites. In some species, local axons have an initiating function in odontogenesis, but it is not known if this is also the case with mammals. In diphyodont mammals, the primary dentition is replaced by a permanent dentition, which involves a profound remodeling of terminal pulpal axons. The molecular signals underlying this remodeling remain unknown. Due to the senescent deterioration of the dentition, the target area of tooth nerves shrinks with age, and these nerves show marked pathological-like changes. Nerve growth factor and possibly also brain-derived neurotrophic factor seem to be important in the formation of a sensory pulpal innervation. Neurotrophin-3 and -4/5 are probably not involved. In addition, glial cell line-derived neurotrophic factor, but not neurturin, seems to be involved in the control of pulpal axon growth. A variety of other growth factors may also influence developing tooth nerves. Many major extracellular matrix molecules, which can influence growing axons, are present in developing teeth. It is likely that these molecules influence the growing pulpal axons.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25076 (URN)10.1177/10454411000110030301 (DOI)9506 (Local ID)9506 (Archive number)9506 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
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