Thomas Carlstedt - Academia.edu (original) (raw)
Papers by Thomas Carlstedt
![Research paper thumbnail of Corrigendum to “Discovery and lead optimisation of a potent, selective and orally bioavailable RARβ agonist for the potential treatment of nerve injury” [Bioorg. Med. Chem. Lett. 29(8) (2019) 995–1000]](https://attachments.academia-assets.com/112339134/thumbnails/1.jpg)
](Bioorganic & Medicinal Chemistry Letters, Aug 1, 2019
Orthopaedic Proceedings, Sep 1, 2005
Introduction: To determine the aetiology of peripheral nerve injuries presenting to a specialist ... more Introduction: To determine the aetiology of peripheral nerve injuries presenting to a specialist centre, identify the management strategies employed and discuss the functional outcome achieved. Methods: Retrospective review of all children referred to this hospital between 1996–2003 with an acquired nerve injury. Obstetrical brachial plexus palsy was excluded. Results : 100 nerve injuries (94 patients) were identified. The mean age was 9.9yrs (0.5–16yrs). 81 injuries involved the upper limb, 19 the lower limb. Most were due to low energy trauma and associated with fractures or their surgical management. 16% presented with autonomic sympathetic dysfunction, 10% with neuropathic pain. 43 patients underwent at least one surgical procedure. The operation was classified diagnostic in 5 (no surgically remediable lesion identified), therapeutic in 33 (surgical procedure could be expected to aid recovery) and reconstructive in 5 (no improvement in nerve function could be achieved; functional improvement achieved by other means). Excellent functional outcome only occurred in conservatively treated cases and in some treated by neurolysis. Nerve grafts and direct repairs were associated with good outcomes. Delayed surgery was associated with fair outcomes. Discussion: Peripheral nerve injuries in children as in adults require careful, prompt attention to obtain the best outcome. Iatropathic injuries must be acknowledged.
Acta Physiologica Scandinavica, 1977
The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopi... more The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopically. A one shaped protrusion of CNS tissue was found to extend distally into each rootlet for a distance of 100-1000 micrometer. That free segment of a rootlet which when cross sectioned revealed both CNS and PNS constituents was denoted the transitional region (TR). The TR was subdivided into an axial CNS compartment and a surrounding PNS compartment. The CNS compartment consisted of a core zone that showed the organisation of a CNS fiber tract, and of an outer astrocytic mantle zone which corresponded to the external glial limiting membrane of the brain and the spinal cord. The outer aspect of the mantle zone constituted the PNS-CNS borderline. The mantle zone was rich in astrocytes and projected a large number of thin processes--the glial fringe--distally into the endoneural space of the PNS compartment. There were large fenestration defects in the basement membrane that demarcated the endoneural space from the glial space. The mantle zone contained many large myelinoid bodies and some encapsulated small dark unclassified cells. Similar cells, some covered by a basement membrane, were at hand in the adjacent endoneural space. The myelinated nerve fibres were equipped with a node of Ranvier at their borderline passage.
PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO. eBooks, Jun 1, 2007
PubMed, 1977
A preparatory method, considered to preserve the ultrastructure of the transitional region of lum... more A preparatory method, considered to preserve the ultrastructure of the transitional region of lumbosacral dorsal roots in a "useful" way has been tested out. The method consists of vascular perfusion with 5% glutaraldehyde dissolyed in a 300 mOsm Millonig buffer containing 200 mOsm sucrose and 2.7% low molecular dextran, a postfixation in the same medium, a rinse overnight in a normoton phosphate buffer containing 200 mOsm sucrose, an asmication in 2% OsO4 dissolved in a phosphate buffer, an extensive stepwise dehydration starting in 10% acetone and, finally, embedding in Vestopal W.
PubMed, 1977
Unmyelinated (d.r.C) fibres have been investigated electronmicroscopically at their passage from ... more Unmyelinated (d.r.C) fibres have been investigated electronmicroscopically at their passage from the peripheral to the central nervous system in feline S1 dorsal rootlets. The earlier demonstrated rearrangement of C-fibres during their passage along the transitional region (TR) was confirmed by the observation of extensive fibre divergence. The transitional region Schwann cells was calculated to be 10-20 times as high in the TR as in the more distal parts of the rootlets. Analysis of consecutive ultra-thin sections showed that PNS unmyelinated axons 0.8 micrometer or more acquired a myelin sheath as they entered the CNS. Fibres 0.6-0.8 micrometer in diameter appeared to be segmentally myelinated in the CNS. Fibres less than 0.6 micrometer remained unmyelinated at their CNS entrance. A few fibres showed degenerative signs and terminated in the transitional region.
PubMed, 1977
The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopi... more The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopically. A one shaped protrusion of CNS tissue was found to extend distally into each rootlet for a distance of 100-1000 micrometer. That free segment of a rootlet which when cross sectioned revealed both CNS and PNS constituents was denoted the transitional region (TR). The TR was subdivided into an axial CNS compartment and a surrounding PNS compartment. The CNS compartment consisted of a core zone that showed the organisation of a CNS fiber tract, and of an outer astrocytic mantle zone which corresponded to the external glial limiting membrane of the brain and the spinal cord. The outer aspect of the mantle zone constituted the PNS-CNS borderline. The mantle zone was rich in astrocytes and projected a large number of thin processes--the glial fringe--distally into the endoneural space of the PNS compartment. There were large fenestration defects in the basement membrane that demarcated the endoneural space from the glial space. The mantle zone contained many large myelinoid bodies and some encapsulated small dark unclassified cells. Similar cells, some covered by a basement membrane, were at hand in the adjacent endoneural space. The myelinated nerve fibres were equipped with a node of Ranvier at their borderline passage.
Bioorganic & Medicinal Chemistry Letters, Apr 1, 2019
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
The journal of bone and joint surgery, Jun 1, 2006
We investigated the effect of delay before nerve repair on neuropathic pain after injury to the b... more We investigated the effect of delay before nerve repair on neuropathic pain after injury to the brachial plexus. We studied 148 patients, 85 prospectively and 63 retrospectively. The mean number of avulsed spinal nerves was 3.2 (1 to 5). Pain was measured by a linear visual analogue scale and by the peripheral nerve injury scale. Early repair was more effective than delayed repair in the relief from pain and there was a strong correlation between functional recovery and relief from pain.
Experimental Neurology, Oct 1, 2004
Following avulsion of a spinal ventral root, motoneurons that project through the avulsed root ar... more Following avulsion of a spinal ventral root, motoneurons that project through the avulsed root are axotomized. Avulsion between, for example, L2 and L6 leads to denervation of hind limb muscles. Reimplantation of an avulsed root directed to the motoneuron pool resulted in re-ingrowth of some motor axons. However, most motoneurons display retrograde atrophy and subsequently die. Two neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), promote the survival of motoneurons after injury. The long-term delivery of these neurotrophic factors to the motoneurons in the ventral horn of the spinal cord is problematic. One strategy to improve the outcome of the neurosurgical reinsertion of the ventral root following avulsion would involve gene transfer with adeno-associated viral (AAV) vectors encoding these neurotrophic factors near the denervated motoneuron pool. Here, we show that AAVmediated overexpression of GDNF and BDNF in the spinal cord persisted for at least 16 weeks. At both 1 and 4 months post-lesion AAV-BDNF-and-GDNF-treated animals showed an increased survival of motoneurons, the effect being more prominent at 1 month. AAV vectormediated overexpression of neurotrophins also promoted the formation of a network of motoneuron fibers in the ventral horn at the avulsed side, but motoneurons failed to extent axons into the reinserted L4 root towards the sciatic nerve nor to improve functional recovery of the hind limbs. This suggests that high levels of neurotrophic factors in the ventral horn promote sprouting, but prevent directional growth of axons of a higher number of surviving motoneurons into the implanted root.
Springer eBooks, Oct 21, 2013
PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO. eBooks, Jun 1, 2007
Experimental Neurology, Nov 1, 1999
Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This i... more Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Although transplantation of peripheral nerve tissue bridges is perhaps the most successful approach to promoting regeneration in the CNS, ingrowth of CNS nerve fibers with such transplants is limited. Genetic modification of peripheral nerve bridges to overexpress outgrowth-promoting proteins should, in principle, improve the permissive properties of peripheral nerve transplants. The present study shows that pieces of peripheral intercostal nerve, subjected to ex vivo adenoviral vector-mediated gene transfer and implanted as nerve bridges in transected sciatic nerve, avulsed ventral root, hemi-sected spinal cord and intact brain, are capable of expressing a foreign gene. In vitro studies showed expression of the reporter gene LacZ up to 30 days in Schwann cells. After implantation, LacZ expression could be detected at 7 days postimplantation, but had virtually disappeared at 14 days. Schwann cells of the transduced nerve bridges retained the capacity of guiding regenerative peripheral and central nerve fiber ingrowth. Transduction of intercostal nerve pieces prior to implantation should, in principle, enable enhanced local production of neurotrophic factors within the transplant and has the potential to improve the regeneration of injured axons into the graft. 1999 Academic Press
Central Nerve Plexus Injury, 2007
Although a general poor outcome of lesions in mammalian central nervous system there are some int... more Although a general poor outcome of lesions in mammalian central nervous system there are some interesting regional differences in the response to traumatic injury. There are indications that the inflammatory pattern and the duration of traumatic defects in the Blood Brain Barrier are dissimilar in the brain and the spinal cord. In this study we have examined the acute gene expression response in the adult rat after two types of traumatic brain injury (TBI) and two types of lesions affecting the spinal cord. The TBI models were an exposure to blast overpressure (200 kPa), a sagittal acceleration injury and a cortical penetration injury. The spinal injuries were lumbar ventral root avulsion at the border between the CNS and PNS. Ventral root avulsion is not followed by spontaneous regrowth. The second spinal injury was replantation of avulsed spinal ventral roots, enabling significant and useful regrowth of motor axons. In this study we have analyzed the acute response to these 5 types of injury with gene arrays combined with cluster analysis of gene ontology search terms. 3 adult Sprague-Dawley rats for each of the 5 models were used. 24 h after the injury, the animals were anesthetized and the inferior vena cava was cut open. The hippocampus and the cortex were used for analysis of the 3 TBI models and the ipsilateral ventral quadrat of the affected spinal cord segment was used for the spinal injuries. RNA samples were analysed was then hybridized to Affymetrix Rat Gene ST 1.0 array. The data show significant differences between rats subjected to ventral replantation compared to avulsion only. Whereas, the number of genes related to cell death is similar in the two models after 24 hours, we observed a significantly larger number of genes related to neurite growth and development in the rats treated with ventral root replantation. In addition, an acute inflammatory response was observed after avulsion, while effects on genes related to synaptic transmission were much more pronounced after replantation than after avulsion without replantation. Blast overpressure induced limited shifts in gene expression in the hippocampus. The most interesting findings were a down regulation of genes involved in neurogenesis and synaptic transmission. Acceleration and penetration injuries resulted in changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus and the cortex. We, conclude that cluster analysis of gene ontology search terms analysis may facilitate the comparison of the acute response in different types of injury.
Frontiers in Neurology, 2010
PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO. eBooks, Jun 1, 2007
Brain Research Bulletin, 1993
In attempts to correct neural deficits following avulsion trauma, novel experimental strategies w... more In attempts to correct neural deficits following avulsion trauma, novel experimental strategies were developed. In rats, spinal roots were replanted superficially in the dorsal horn following dorsal root avulsion and concomitant denervation by ganglionectomy. Outgrowth from cord neurons in the dorsal horn into the implanted dorsal root was demonstrated by means of retrograde HRP labeling. Double labeling experiments showed that some of these neurons had retained their central projections while extending new processes into the implanted root. After dorsal root avulsion, sensory pathways might be reconstructed by substituting the lost input from damaged primary sensory neurons with induced peripheral outgrowths from secondary neurons. In primates, intraspinal replantation of avulsed ventral nerve roots was investigated as a surgical treatment for motor deficits that develop after severe brachial plexus injury. Two to 3 months after surgery there were EMG signs of reinnervation in previously denervated muscles, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and motor behavior became normalized, although the EMG activity in the reinnervated muscles at maximal contraction was still reduced. The outcome of these experimental studies indicates that reconstructive surgery applied to the brachial plexus might be of value to restore functional deficits induced by traumatic spinal nerve root avulsions also in man.
Bioorganic & Medicinal Chemistry Letters, Aug 1, 2019
Orthopaedic Proceedings, Sep 1, 2005
Introduction: To determine the aetiology of peripheral nerve injuries presenting to a specialist ... more Introduction: To determine the aetiology of peripheral nerve injuries presenting to a specialist centre, identify the management strategies employed and discuss the functional outcome achieved. Methods: Retrospective review of all children referred to this hospital between 1996–2003 with an acquired nerve injury. Obstetrical brachial plexus palsy was excluded. Results : 100 nerve injuries (94 patients) were identified. The mean age was 9.9yrs (0.5–16yrs). 81 injuries involved the upper limb, 19 the lower limb. Most were due to low energy trauma and associated with fractures or their surgical management. 16% presented with autonomic sympathetic dysfunction, 10% with neuropathic pain. 43 patients underwent at least one surgical procedure. The operation was classified diagnostic in 5 (no surgically remediable lesion identified), therapeutic in 33 (surgical procedure could be expected to aid recovery) and reconstructive in 5 (no improvement in nerve function could be achieved; functional improvement achieved by other means). Excellent functional outcome only occurred in conservatively treated cases and in some treated by neurolysis. Nerve grafts and direct repairs were associated with good outcomes. Delayed surgery was associated with fair outcomes. Discussion: Peripheral nerve injuries in children as in adults require careful, prompt attention to obtain the best outcome. Iatropathic injuries must be acknowledged.
Acta Physiologica Scandinavica, 1977
The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopi... more The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopically. A one shaped protrusion of CNS tissue was found to extend distally into each rootlet for a distance of 100-1000 micrometer. That free segment of a rootlet which when cross sectioned revealed both CNS and PNS constituents was denoted the transitional region (TR). The TR was subdivided into an axial CNS compartment and a surrounding PNS compartment. The CNS compartment consisted of a core zone that showed the organisation of a CNS fiber tract, and of an outer astrocytic mantle zone which corresponded to the external glial limiting membrane of the brain and the spinal cord. The outer aspect of the mantle zone constituted the PNS-CNS borderline. The mantle zone was rich in astrocytes and projected a large number of thin processes--the glial fringe--distally into the endoneural space of the PNS compartment. There were large fenestration defects in the basement membrane that demarcated the endoneural space from the glial space. The mantle zone contained many large myelinoid bodies and some encapsulated small dark unclassified cells. Similar cells, some covered by a basement membrane, were at hand in the adjacent endoneural space. The myelinated nerve fibres were equipped with a node of Ranvier at their borderline passage.
PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO. eBooks, Jun 1, 2007
PubMed, 1977
A preparatory method, considered to preserve the ultrastructure of the transitional region of lum... more A preparatory method, considered to preserve the ultrastructure of the transitional region of lumbosacral dorsal roots in a "useful" way has been tested out. The method consists of vascular perfusion with 5% glutaraldehyde dissolyed in a 300 mOsm Millonig buffer containing 200 mOsm sucrose and 2.7% low molecular dextran, a postfixation in the same medium, a rinse overnight in a normoton phosphate buffer containing 200 mOsm sucrose, an asmication in 2% OsO4 dissolved in a phosphate buffer, an extensive stepwise dehydration starting in 10% acetone and, finally, embedding in Vestopal W.
PubMed, 1977
Unmyelinated (d.r.C) fibres have been investigated electronmicroscopically at their passage from ... more Unmyelinated (d.r.C) fibres have been investigated electronmicroscopically at their passage from the peripheral to the central nervous system in feline S1 dorsal rootlets. The earlier demonstrated rearrangement of C-fibres during their passage along the transitional region (TR) was confirmed by the observation of extensive fibre divergence. The transitional region Schwann cells was calculated to be 10-20 times as high in the TR as in the more distal parts of the rootlets. Analysis of consecutive ultra-thin sections showed that PNS unmyelinated axons 0.8 micrometer or more acquired a myelin sheath as they entered the CNS. Fibres 0.6-0.8 micrometer in diameter appeared to be segmentally myelinated in the CNS. Fibres less than 0.6 micrometer remained unmyelinated at their CNS entrance. A few fibres showed degenerative signs and terminated in the transitional region.
PubMed, 1977
The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopi... more The aproximal segment of feline S1 dorsal rootlets were investigated light and electronmicroscopically. A one shaped protrusion of CNS tissue was found to extend distally into each rootlet for a distance of 100-1000 micrometer. That free segment of a rootlet which when cross sectioned revealed both CNS and PNS constituents was denoted the transitional region (TR). The TR was subdivided into an axial CNS compartment and a surrounding PNS compartment. The CNS compartment consisted of a core zone that showed the organisation of a CNS fiber tract, and of an outer astrocytic mantle zone which corresponded to the external glial limiting membrane of the brain and the spinal cord. The outer aspect of the mantle zone constituted the PNS-CNS borderline. The mantle zone was rich in astrocytes and projected a large number of thin processes--the glial fringe--distally into the endoneural space of the PNS compartment. There were large fenestration defects in the basement membrane that demarcated the endoneural space from the glial space. The mantle zone contained many large myelinoid bodies and some encapsulated small dark unclassified cells. Similar cells, some covered by a basement membrane, were at hand in the adjacent endoneural space. The myelinated nerve fibres were equipped with a node of Ranvier at their borderline passage.
Bioorganic & Medicinal Chemistry Letters, Apr 1, 2019
If citing, it is advised that you check and use the publisher's definitive version for pagination... more If citing, it is advised that you check and use the publisher's definitive version for pagination, volume/issue, and date of publication details. And where the final published version is provided on the Research Portal, if citing you are again advised to check the publisher's website for any subsequent corrections.
The journal of bone and joint surgery, Jun 1, 2006
We investigated the effect of delay before nerve repair on neuropathic pain after injury to the b... more We investigated the effect of delay before nerve repair on neuropathic pain after injury to the brachial plexus. We studied 148 patients, 85 prospectively and 63 retrospectively. The mean number of avulsed spinal nerves was 3.2 (1 to 5). Pain was measured by a linear visual analogue scale and by the peripheral nerve injury scale. Early repair was more effective than delayed repair in the relief from pain and there was a strong correlation between functional recovery and relief from pain.
Experimental Neurology, Oct 1, 2004
Following avulsion of a spinal ventral root, motoneurons that project through the avulsed root ar... more Following avulsion of a spinal ventral root, motoneurons that project through the avulsed root are axotomized. Avulsion between, for example, L2 and L6 leads to denervation of hind limb muscles. Reimplantation of an avulsed root directed to the motoneuron pool resulted in re-ingrowth of some motor axons. However, most motoneurons display retrograde atrophy and subsequently die. Two neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), promote the survival of motoneurons after injury. The long-term delivery of these neurotrophic factors to the motoneurons in the ventral horn of the spinal cord is problematic. One strategy to improve the outcome of the neurosurgical reinsertion of the ventral root following avulsion would involve gene transfer with adeno-associated viral (AAV) vectors encoding these neurotrophic factors near the denervated motoneuron pool. Here, we show that AAVmediated overexpression of GDNF and BDNF in the spinal cord persisted for at least 16 weeks. At both 1 and 4 months post-lesion AAV-BDNF-and-GDNF-treated animals showed an increased survival of motoneurons, the effect being more prominent at 1 month. AAV vectormediated overexpression of neurotrophins also promoted the formation of a network of motoneuron fibers in the ventral horn at the avulsed side, but motoneurons failed to extent axons into the reinserted L4 root towards the sciatic nerve nor to improve functional recovery of the hind limbs. This suggests that high levels of neurotrophic factors in the ventral horn promote sprouting, but prevent directional growth of axons of a higher number of surviving motoneurons into the implanted root.
Springer eBooks, Oct 21, 2013
PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO. eBooks, Jun 1, 2007
Experimental Neurology, Nov 1, 1999
Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This i... more Axons of the CNS do normally not regenerate after injury, in contrast to axons of the PNS. This is due to a different microenvironment at the site of the lesion as well as a particular intrinsic program of axonal regrowth. Although transplantation of peripheral nerve tissue bridges is perhaps the most successful approach to promoting regeneration in the CNS, ingrowth of CNS nerve fibers with such transplants is limited. Genetic modification of peripheral nerve bridges to overexpress outgrowth-promoting proteins should, in principle, improve the permissive properties of peripheral nerve transplants. The present study shows that pieces of peripheral intercostal nerve, subjected to ex vivo adenoviral vector-mediated gene transfer and implanted as nerve bridges in transected sciatic nerve, avulsed ventral root, hemi-sected spinal cord and intact brain, are capable of expressing a foreign gene. In vitro studies showed expression of the reporter gene LacZ up to 30 days in Schwann cells. After implantation, LacZ expression could be detected at 7 days postimplantation, but had virtually disappeared at 14 days. Schwann cells of the transduced nerve bridges retained the capacity of guiding regenerative peripheral and central nerve fiber ingrowth. Transduction of intercostal nerve pieces prior to implantation should, in principle, enable enhanced local production of neurotrophic factors within the transplant and has the potential to improve the regeneration of injured axons into the graft. 1999 Academic Press
Central Nerve Plexus Injury, 2007
Although a general poor outcome of lesions in mammalian central nervous system there are some int... more Although a general poor outcome of lesions in mammalian central nervous system there are some interesting regional differences in the response to traumatic injury. There are indications that the inflammatory pattern and the duration of traumatic defects in the Blood Brain Barrier are dissimilar in the brain and the spinal cord. In this study we have examined the acute gene expression response in the adult rat after two types of traumatic brain injury (TBI) and two types of lesions affecting the spinal cord. The TBI models were an exposure to blast overpressure (200 kPa), a sagittal acceleration injury and a cortical penetration injury. The spinal injuries were lumbar ventral root avulsion at the border between the CNS and PNS. Ventral root avulsion is not followed by spontaneous regrowth. The second spinal injury was replantation of avulsed spinal ventral roots, enabling significant and useful regrowth of motor axons. In this study we have analyzed the acute response to these 5 types of injury with gene arrays combined with cluster analysis of gene ontology search terms. 3 adult Sprague-Dawley rats for each of the 5 models were used. 24 h after the injury, the animals were anesthetized and the inferior vena cava was cut open. The hippocampus and the cortex were used for analysis of the 3 TBI models and the ipsilateral ventral quadrat of the affected spinal cord segment was used for the spinal injuries. RNA samples were analysed was then hybridized to Affymetrix Rat Gene ST 1.0 array. The data show significant differences between rats subjected to ventral replantation compared to avulsion only. Whereas, the number of genes related to cell death is similar in the two models after 24 hours, we observed a significantly larger number of genes related to neurite growth and development in the rats treated with ventral root replantation. In addition, an acute inflammatory response was observed after avulsion, while effects on genes related to synaptic transmission were much more pronounced after replantation than after avulsion without replantation. Blast overpressure induced limited shifts in gene expression in the hippocampus. The most interesting findings were a down regulation of genes involved in neurogenesis and synaptic transmission. Acceleration and penetration injuries resulted in changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus and the cortex. We, conclude that cluster analysis of gene ontology search terms analysis may facilitate the comparison of the acute response in different types of injury.
Frontiers in Neurology, 2010
PUBLISHED BY IMPERIAL COLLEGE PRESS AND DISTRIBUTED BY WORLD SCIENTIFIC PUBLISHING CO. eBooks, Jun 1, 2007
Brain Research Bulletin, 1993
In attempts to correct neural deficits following avulsion trauma, novel experimental strategies w... more In attempts to correct neural deficits following avulsion trauma, novel experimental strategies were developed. In rats, spinal roots were replanted superficially in the dorsal horn following dorsal root avulsion and concomitant denervation by ganglionectomy. Outgrowth from cord neurons in the dorsal horn into the implanted dorsal root was demonstrated by means of retrograde HRP labeling. Double labeling experiments showed that some of these neurons had retained their central projections while extending new processes into the implanted root. After dorsal root avulsion, sensory pathways might be reconstructed by substituting the lost input from damaged primary sensory neurons with induced peripheral outgrowths from secondary neurons. In primates, intraspinal replantation of avulsed ventral nerve roots was investigated as a surgical treatment for motor deficits that develop after severe brachial plexus injury. Two to 3 months after surgery there were EMG signs of reinnervation in previously denervated muscles, which were shortly followed by evidence of clinical recovery. A gradual improvement in the function of the affected arm occurred and motor behavior became normalized, although the EMG activity in the reinnervated muscles at maximal contraction was still reduced. The outcome of these experimental studies indicates that reconstructive surgery applied to the brachial plexus might be of value to restore functional deficits induced by traumatic spinal nerve root avulsions also in man.