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Article ; Online: Ethics and accountability for clinical trials.

Barretto, Tanya A / Tetzlaff, Wolfram / Illes, Judy

2024 Volume 62, Issue 4, Page(s) 192–194

Abstract: In May 2023, a disclaimer posted on ClinicalTrials.gov dismisses accountability for the accuracy of registered information. For spinal cord injury, inconsistencies in intervention classification, phase designation, and lack of study protocols and results ...

Abstract	In May 2023, a disclaimer posted on ClinicalTrials.gov dismisses accountability for the accuracy of registered information. For spinal cord injury, inconsistencies in intervention classification, phase designation, and lack of study protocols and results threaten the integrity of the database and put users at risk. An investment in what the resource should be rather than what it is not will give it the authority commensurate with the requirements for its regulatory use and informed decision-making for prospective trial participants.
MeSH term(s)	Humans ; Prospective Studies ; Spinal Cord Injuries/therapy ; Social Responsibility
Language	English
Publishing date	2024-03-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1316161-1
ISSN	1476-5624 ; 1362-4393
ISSN (online)	1476-5624
ISSN	1362-4393
DOI	10.1038/s41393-024-00980-z
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Article ; Online: A brainstem bypass for spinal cord injury.

Hilton, Brett J / Tetzlaff, Wolfram

Nature neuroscience

2018 Volume 21, Issue 4, Page(s) 457–458

MeSH term(s)	Brain Stem ; Humans ; Recovery of Function ; Spinal Cord Injuries
Language	English
Publishing date	2018-03-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1420596-8
ISSN	1546-1726 ; 1097-6256
ISSN (online)	1546-1726
ISSN	1097-6256
DOI	10.1038/s41593-018-0099-z
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Zs.A 4891: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 67: Show issues

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Book: Tight Junction und Gap Junction Kontakte in den Nervenfasern des Nervus Ischiadicus des Huehnchens waehrend der Myelogenese, Wallerschen Degeneration und nachfolgenden Regeneration

Tetzlaff, Wolfram

1980

Size	90 BL. : ILL., GRAPH. DARST.
Document type	Book
Note	BOCHUM, UNIV., DISS., 1981
HBZ-ID	HT002604445
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Article ; Online: HDAC inhibition leads to age-dependent opposite regenerative effect upon PTEN deletion in rubrospinal axons after SCI.

Seira, Oscar / Wang, Wenchun / Lee, Sharon / Roskams, Jane / Tetzlaff, Wolfram

Neurobiology of aging

2020 Volume 90, Page(s) 99–109

Abstract: Epigenetic changes associated with aging have been linked to functional and cognitive deficits in the adult CNS. Histone acetylation is involved in the control of the transcription of plasticity and regeneration-associated genes. The intrinsic axon ... ...

Abstract	Epigenetic changes associated with aging have been linked to functional and cognitive deficits in the adult CNS. Histone acetylation is involved in the control of the transcription of plasticity and regeneration-associated genes. The intrinsic axon growth capacity in the CNS is negatively regulated by phosphatase and tensin homolog (Pten). Inhibition of Pten is an effective method to stimulate axon growth following an injury to the optic nerve, corticospinal tract (CST), and rubrospinal tract (RST). Our laboratory has previously demonstrated that the deletion of Pten in aged animals diminishes the regenerative capacity in rubrospinal neurons. We hypothesize that changes in the chromatin structure might contribute to this age-associated decline. Here, we assessed whether Trichostatin A (TSA), a histone deacetylases (HDACs) inhibitor, reverses the decline in regeneration in aged Pten
MeSH term(s)	Aging/genetics ; Aging/physiology ; Animals ; Axons/metabolism ; Axons/physiology ; GAP-43 Protein/genetics ; GAP-43 Protein/metabolism ; Gene Deletion ; Gene Expression/drug effects ; Histone Deacetylase Inhibitors/adverse effects ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/pharmacology ; Histone Deacetylases/physiology ; Hydroxamic Acids/adverse effects ; Hydroxamic Acids/pharmacology ; Mice, Transgenic ; Motor Activity/drug effects ; Nerve Regeneration/drug effects ; Nerve Regeneration/genetics ; PTEN Phosphohydrolase/genetics ; Recovery of Function/drug effects ; Recovery of Function/genetics ; Spinal Cord/metabolism ; Spinal Cord Injuries/genetics ; Spinal Cord Injuries/physiopathology
Chemical Substances	GAP-43 Protein ; Histone Deacetylase Inhibitors ; Hydroxamic Acids ; trichostatin A (3X2S926L3Z) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; Pten protein, mouse (EC 3.1.3.67) ; Histone Deacetylases (EC 3.5.1.98)
Language	English
Publishing date	2020-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	604505-4
ISSN	1558-1497 ; 0197-4580
ISSN (online)	1558-1497
ISSN	0197-4580
DOI	10.1016/j.neurobiolaging.2020.02.006
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Zs.A 1685: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 10: Show issues

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Article: Diversity of Reactive Astrogliosis in CNS Pathology: Heterogeneity or Plasticity?

Moulson, Aaron J / Squair, Jordan W / Franklin, Robin J M / Tetzlaff, Wolfram / Assinck, Peggy

Frontiers in cellular neuroscience

2021 Volume 15, Page(s) 703810

Abstract: Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as "reactive astrogliosis." Diversity ... ...

Abstract	Astrocytes are essential for the development and homeostatic maintenance of the central nervous system (CNS). They are also critical players in the CNS injury response during which they undergo a process referred to as "reactive astrogliosis." Diversity in astrocyte morphology and gene expression, as revealed by transcriptional analysis, is well-recognized and has been reported in several CNS pathologies, including ischemic stroke, CNS demyelination, and traumatic injury. This diversity appears unique to the specific pathology, with significant variance across temporal, topographical, age, and sex-specific variables. Despite this, there is limited functional data corroborating this diversity. Furthermore, as reactive astrocytes display significant environmental-dependent plasticity and fate-mapping data on astrocyte subsets in the adult CNS is limited, it remains unclear whether this diversity represents heterogeneity or plasticity. As astrocytes are important for neuronal survival and CNS function post-injury, establishing to what extent this diversity reflects distinct established heterogeneous astrocyte subpopulations vs. environmentally dependent plasticity within established astrocyte subsets will be critical for guiding therapeutic development. To that end, we review the current state of knowledge on astrocyte diversity in the context of three representative CNS pathologies: ischemic stroke, demyelination, and traumatic injury, with the goal of identifying key limitations in our current knowledge and suggesting future areas of research needed to address them. We suggest that the majority of identified astrocyte diversity in CNS pathologies to date represents plasticity in response to dynamically changing post-injury environments as opposed to heterogeneity, an important consideration for the understanding of disease pathogenesis and the development of therapeutic interventions.
Language	English
Publishing date	2021-07-26
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2021.703810
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Article ; Online: Temporal Progression of Acute Spinal Cord Injury Mechanisms in a Rat Model: Contusion, Dislocation, and Distraction.

Mattucci, Stephen / Speidel, Jason / Liu, Jie / Tetzlaff, Wolfram / Oxland, Thomas R

Journal of neurotrauma

2021 Volume 38, Issue 15, Page(s) 2103–2121

Abstract: Traumatic spinal cord injuries (SCIs) occur due to different spinal column injury patterns, including burst fracture, dislocation, and flexion-distraction. Pre-clinical studies modeling different SCI mechanisms have shown distinct histological ... ...

Abstract	Traumatic spinal cord injuries (SCIs) occur due to different spinal column injury patterns, including burst fracture, dislocation, and flexion-distraction. Pre-clinical studies modeling different SCI mechanisms have shown distinct histological differences between these injuries both acutely (3 h and less) and chronically (8 weeks), but there remains a temporal gap. Different rates of injury progression at specific regions of the spinal cord may provide insight into the pathologies that are initiated by specific SCI mechanisms. Therefore, the objective of this study was to evaluate the temporal progression of injury at specific tracts within the white matter, for time-points of 3 h, 24 h, and 7 days, for three distinct SCI mechanisms. In this study, 96 male Sprague Dawley rats underwent one of three SCI mechanisms: contusion, dislocation, or distraction. Animals were sacrificed at one of three times post-injury: 3 h, 24 h, or 7 days. Histological analysis using eriochrome cyanide and immunostaining for MBP, SMI-312, neurofilament-H (NF-H), and β-III tubulin were used to characterize white matter sparing and axon and myelinated axon counts. The regions analyzed were the gracile fasciculus, cuneate fasciculus, dorsal corticospinal tract, and ventrolateral white matter. Contusion, dislocation, and distraction SCIs demonstrated distinct damage patterns that progressed differently over time. Myelinated axon counts were significantly reduced after dislocation and contusion injuries in most locations and time-points analyzed (compared with sham). This indicates early myelin damage often within 3 h. Myelinated axon counts after distraction dropped early and did not demonstrate any significant progression over the next 7 days. Important differences in white matter degeneration were identified between injury types, with distraction injuries showing the least variability across time-points These findings and the observation that white matter injury occurs early, and in many cases, without much dynamic change, highlight the importance of injury type in SCI research-both clinically and pre-clinically.
MeSH term(s)	Animals ; Disease Models, Animal ; Disease Progression ; Male ; Rats ; Rats, Sprague-Dawley ; Spinal Cord Injuries/etiology ; Spinal Cord Injuries/pathology ; Time Factors ; White Matter/pathology
Language	English
Publishing date	2021-06-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645092-1
ISSN	1557-9042 ; 0897-7151
ISSN (online)	1557-9042
ISSN	0897-7151
DOI	10.1089/neu.2020.7255
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Article ; Online: KIF2A characterization after spinal cord injury.

Seira, Oscar / Liu, Jie / Assinck, Peggy / Ramer, Matt / Tetzlaff, Wolfram

Cellular and molecular life sciences : CMLS

2019 Volume 76, Issue 21, Page(s) 4355–4368

Abstract: Axons in the central nervous system (CNS) typically fail to regenerate after injury. This failure is multi-factorial and caused in part by disruption of the axonal cytoskeleton. The cytoskeleton, in particular microtubules (MT), plays a critical role in ... ...

Abstract	Axons in the central nervous system (CNS) typically fail to regenerate after injury. This failure is multi-factorial and caused in part by disruption of the axonal cytoskeleton. The cytoskeleton, in particular microtubules (MT), plays a critical role in axonal transport and axon growth during development. In this regard, members of the kinesin superfamily of proteins (KIFs) regulate the extension of primary axons toward their targets and control the growth of collateral branches. KIF2A negatively regulates axon growth through MT depolymerization. Using three different injury models to induce SCI in adult rats, we examined the temporal and cellular expression of KIF2A in the injured spinal cord. We observed a progressive increase of KIF2A expression with maximal levels at 10 days to 8 weeks post-injury as determined by Western blot analysis. KIF2A immunoreactivity was present in axons, spinal neurons and mature oligodendrocytes adjacent to the injury site. Results from the present study suggest that KIF2A at the injured axonal tips may contribute to neurite outgrowth inhibition after injury, and that its increased expression in inhibitory spinal neurons adjacent to the injury site might contribute to an intrinsic wiring-control mechanism associated with neuropathic pain. Further studies will determine whether KIF2A may be a potential target for the development of regeneration-promoting or pain-preventing therapies.
MeSH term(s)	Animals ; Axons/metabolism ; Axons/pathology ; Disease Models, Animal ; Kinesin/analysis ; Kinesin/genetics ; Kinesin/metabolism ; Male ; Nerve Regeneration/genetics ; Neurons/metabolism ; Neurons/pathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/metabolism ; Spinal Cord/pathology ; Spinal Cord Injuries/genetics ; Spinal Cord Injuries/metabolism ; Spinal Cord Injuries/pathology
Chemical Substances	Kif2a protein, rat ; Kinesin (EC 3.6.4.4)
Language	English
Publishing date	2019-04-30
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1358415-7
ISSN	1420-9071 ; 1420-682X
ISSN (online)	1420-9071
ISSN	1420-682X
DOI	10.1007/s00018-019-03116-2
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Article ; Online: Neuroprotection and secondary damage following spinal cord injury: concepts and methods.

Hilton, Brett J / Moulson, Aaron J / Tetzlaff, Wolfram

Neuroscience letters

2017 Volume 652, Page(s) 3–10

Abstract: Neuroprotection refers to the attenuation of pathophysiological processes triggered by acute injury to minimize secondary damage. The development of neuroprotective treatments represents a major goal in the field of spinal cord injury (SCI) research. In ... ...

Abstract	Neuroprotection refers to the attenuation of pathophysiological processes triggered by acute injury to minimize secondary damage. The development of neuroprotective treatments represents a major goal in the field of spinal cord injury (SCI) research. In this review, we discuss the strengths and limitations of the methodologies employed to assess secondary damage and neuroprotection in preclinical models of traumatic SCI. We also discuss modelling issues and how new tools might be exploited to study secondary damage and neuroprotection.
Language	English
Publishing date	2017-06-23
Publishing country	Ireland
Document type	Journal Article ; Review
ZDB-ID	194929-9
ISSN	1872-7972 ; 0304-3940
ISSN (online)	1872-7972
ISSN	0304-3940
DOI	10.1016/j.neulet.2016.12.004
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Article ; Online: Regeneration-associated genes decline in chronically injured rat sciatic motoneurons.

Gordon, Tessa / Tetzlaff, Wolfram

The European journal of neuroscience

2015 Volume 42, Issue 10, Page(s) 2783–2791

Abstract: Chronic nerve injuries are notorious for their poor regenerative outcomes. Here, we addressed the question of whether the established reduced ability of injured motoneurons to regenerate their axons with time of disconnection with targets (chronic ... ...

Abstract	Chronic nerve injuries are notorious for their poor regenerative outcomes. Here, we addressed the question of whether the established reduced ability of injured motoneurons to regenerate their axons with time of disconnection with targets (chronic axotomy) is associated with a failure of injured motoneurons to express and sustain their expression of regeneration-associated genes. Sciatic motoneurons were prevented from regenerating by ligation of the transected nerves (chronic axotomy), and then subjected to a second nerve transection (acute axotomy) to mimic the clinical surgical procedure of refreshing the proximal nerve stump prior to delayed nerve repair. The expression of α1-tubulin, actin and GAP-43 mRNA was analysed in axotomized sciatic motoneurons by the use of in situ hybridization followed by autoradiography and silver grain quantification. The expression of these regeneration-associated genes by naive (acutely) axotomized motoneurons declined exponentially, to reach baseline levels within 6 months. These chronically injured motoneurons responded to a refreshment axotomy by elevating the expression of the genes to the same levels as in acutely (i.e. for the first time) axotomized sciatic motoneurons. However, the expression of these declined more rapidly than after acute axotomy. We conclude that a progressive decline in the expression of the regeneration-associated genes in chronically axotomized motoneurons and the even more rapid decline in their expression in response to a refreshment axotomy may explain why the regenerative capacity of chronically axotomized neurons declines with time.
MeSH term(s)	Actins/metabolism ; Animals ; Axotomy ; Female ; GAP-43 Protein/metabolism ; Motor Neurons/metabolism ; Nerve Regeneration ; RNA, Messenger/metabolism ; Rats ; Rats, Sprague-Dawley ; Sciatic Neuropathy/genetics ; Sciatic Neuropathy/metabolism ; Tubulin/metabolism ; Up-Regulation
Chemical Substances	Actins ; GAP-43 Protein ; RNA, Messenger ; Tubulin
Language	English
Publishing date	2015-11
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	645180-9
ISSN	1460-9568 ; 0953-816X
ISSN (online)	1460-9568
ISSN	0953-816X
DOI	10.1111/ejn.13070
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Zs.A 2548: Show issues

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Article ; Online: Distribution of gastrointestinal neuroendocrine tumors in Europe: results from a retrospective cross-sectional study

Loosen, Sven H. / Kostev, Karel / Jann, Henning / Tetzlaff, Fabian / Tacke, Frank / Krieg, Sarah / Knoefel, Wolfram T. / Fluegen, Georg / Luedde, Tom / Krieg, Andreas / Roderburg, Christoph

J Cancer Res Clin Oncol. 2023 Apr., v. 149, no. 4, p. 1411-1416

2023 , Page(s) 1411–1416

Abstract: BACKGROUND: Gastrointestinal (non-pancreatic) neuroendocrine tumors (GI-NETs) represent a rare but increasingly common tumor entity. Prognosis and biological behavior of these tumors is extremely heterogenous and largely dependent on the specific tumor ... ...

Abstract	BACKGROUND: Gastrointestinal (non-pancreatic) neuroendocrine tumors (GI-NETs) represent a rare but increasingly common tumor entity. Prognosis and biological behavior of these tumors is extremely heterogenous and largely dependent on the specific tumor site, stage and differentiation. However, systematic data on the epidemiology of GI-NET, especially in terms of geographic distributions are missing. METHODS: We used the Oncology Dynamics database (IQVIA) to identify a total of 1354 patients with GI-NET from four European countries (Germany, France, Spain, UK) and compared them with regard to major patient and tumor related characteristics including patients’ age, sex, tumor stage, tumor grading and differentiation. RESULTS: Out of the analyzed 1354 NET patients, 535 were found in the UK (39.5%), 289 in Germany (21.3%), 283 in Spain (20.9%) and 247 in France (18.2%). More patients were male than female (53.8% vs. 46.2%) with no significant differences between the analyzed countries. In contrast, the age distribution varied between the different countries, with the highest number of patients identified in the age groups of 61–70 years (31.0%) and 71–80 years (30.7%). The vast majority of patients showed a tumor origin in the small intestine, in German patients NET of the large intestine were slightly overrepresented and NET of the stomach underrepresented compared to all other countries. More than 80% of patients had stage IV disease at the time of diagnosis. Regarding tumor histology, most tumors showed a G2 tumor; interestingly, a G3 grading was found in 40.9% of patients in Germany (Ki-67 > 20%). CONCLUSION: The distribution of important patient- and tumor-specific characteristics of neuroendocrine tumors shows regional differences in four major European countries. These data may help to better understand the specific epidemiology of GI-NET in Europe.
Keywords	cross-sectional studies ; databases ; epidemiology ; females ; histology ; large intestine ; males ; neoplasms ; patients ; prognosis ; small intestine ; stomach ; France ; Germany ; Spain
Language	English
Dates of publication	2023-04
Size	p. 1411-1416
Publishing place	Springer Berlin Heidelberg
Document type	Article ; Online
ZDB-ID	134792-5
ISSN	1432-1335 ; 0171-5216 ; 0084-5353 ; 0943-9382
ISSN (online)	1432-1335
ISSN	0171-5216 ; 0084-5353 ; 0943-9382
DOI	10.1007/s00432-022-04003-3
Database	NAL-Catalogue (AGRICOLA)

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