A5036413274- Nerve injury and regeneration
- Spinal Cord Injury Research
- Neurogenesis and neuroplasticity mechanisms
- Pain Mechanisms and Treatments
- Histone Deacetylase Inhibitors Research
- Signaling Pathways in Disease
- Nerve Injury and Rehabilitation
- Tissue Engineering and Regenerative Medicine
- Axon Guidance and Neuronal Signaling
- Cerebral Palsy and Movement Disorders
- Zebrafish Biomedical Research Applications
- Musculoskeletal pain and rehabilitation
- Genetic Neurodegenerative Diseases
- Stroke Rehabilitation and Recovery
- Mitochondrial Function and Pathology
- Botulinum Toxin and Related Neurological Disorders
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Cellular Mechanics and Interactions
- Retinoids in leukemia and cellular processes
- Mesenchymal stem cell research
- Genetics and Neurodevelopmental Disorders
- Genomic variations and chromosomal abnormalities
- Neuroinflammation and Neurodegeneration Mechanisms
- Virus-based gene therapy research
Heidelberg University
2017-2024
University Hospital Heidelberg
2017-2024
Hertie Institute for Clinical Brain Research
2008-2020
University of Tübingen
2011-2020
University of Michigan
2000-2003
Columbia University
2000
Max Planck Institute of Neurobiology
2000
Lawrence Livermore National Laboratory
2000
Aging is associated with increased prevalence of axonal injuries characterized by poor regeneration and disability. However, the underlying mechanisms remain unclear. In our experiments, RNA sequencing sciatic dorsal root ganglia (DRG) revealed significant aging-dependent enrichment in T cell signaling both before after nerve injury (SNI) mice. Lymphotoxin activated transcription factor NF-κB, which induced expression chemokine CXCL13 neurons. This turn recruited CXCR5
Regeneration of injured central nervous system axons is highly restricted, causing neurological impairment. To date, although the lack intrinsic regenerative potential well described, a key regulatory molecular mechanism for enhancement both axonal regrowth and functional recovery after injury remains elusive. While ubiquitin ligases coordinate neuronal morphogenesis connectivity during development as injury, their role specifically in regeneration unknown. Following bioinformatics network...
A large proportion of patients suffering from spinal cord injury (SCI) develop chronic central neuropathic pain. Previously, we and others have shown that sensorimotor training early after SCI can prevent the development mechanical allodynia. To determine whether initiated in subchronic/chronic phase remains effective, correlates below-level pain were analyzed hindpaws 5–10 weeks a moderate T11 contusion (50 kDyn) adult female C57BL/6 mice. In comparison sham mice 5 post-injury, about 80%...
In many preclinical spinal cord injury (SCI) studies, assessment of locomotion recovery is key to understanding the effectiveness experimental intervention. such rat SCI most basic locomotor scoring system a subjective observation animals freely roaming in an open field, Basso Beattie Bresnahan (BBB) score. comparison, CatWalk automated gait analysis system, providing further parameter specifications. Although together parameters encompass gait, studies consistently report single parameters,...
Following an acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. This is due to extrinsic inhibitory growth environment the lack of intrinsic competence. Retinoic acid (RA) signaling, essential in developmental dorsoventral patterning specification spinal motor neurons, has been shown through its receptor, transcription factor RA receptor β2 (RARß2), induce following cord injury (SCI). Recently, it that dorsal root ganglia cAMP levels were...
Axonal bridging across a lesion in the injured spinal cord requires growth substrate and guidance cues. Using alginate hydrogels with capillary channels we show that poly-l-ornithine laminin can be stably bound improve cell adhesion neurite vitro, axon vivo by enhancing host infiltration cord. Filling of coated postnatal astrocytes further increases short-distance results continuous astroglial host/graft interface. Thus, positively charged bioactive molecules to anisotropic early promote...
After an acute central nervous system injury, axonal regeneration is limited as the result of a lack neuronal intrinsic competence and presence extrinsic inhibitory signals. The injury fragments myelin insulating layer, releasing molecules to signal through membrane–bound Nogo receptor (NgR) complex. In this paper, we show that transcriptional pathway can interfere with myelin-dependent signaling, thereby promoting neurite outgrowth. Specifically, retinoic acid (RA), acting RA β (RAR-β),...
Abstract The regulatory mechanisms responsible for the gene expression pattern associated with axotomy-dependent signaling affecting neuronal phenotype, including axonal regenerative program, remain unclear. To further this understanding, we recently performed DNA methylation temporal profiling in lumbar dorsal root ganglia (DRG) after axotomy of central spinal (non-regenerating) and peripheral sciatic nerve (regenerating) branches. microarrays mouse promoters CpG islands (Roche/NimbleGen)...
A cosmid/bacterial artificial chromosome (BAC) contiguous (contig) map of human (HSA) 19p13.3 has been constructed, and over 50 genes have localized to the contig. Genes anonymous ESTs from approximately 4000 kb were placed on central mouse 10 by genetic mapping pulsed-field gel electrophoresis (PFGE) analysis. region 2500 HSA is collinear (MMU) 10. In contrast, adjacent 1200 are inverted. Two located in a 50-kb after inversion MMU 10, followed homology 17. The synteny breakpoint one...
The central nervous system (CNS) does not recover from traumatic axonal injury, but the peripheral (PNS) does. We hypothesize that this fundamental difference in regenerative capacity may be based upon absence of stimulatory mechanical forces CNS due to protective rigidity vertebral column and skull. developed a bioreactor apply low-strain cyclic stretch adult rat dorsal root ganglia (DRG) connected either or nerves an explant model for inducing growth. In response, larger diameter DRG...
Adult mammalian CNS neurons are unable to regenerate following axonal injury, leading permanent functional impairments. Yet, the reasons underlying this regeneration failure not fully understood. Here, we study transcriptome and translatome shortly after spinal cord injury. Profiling of total ribosome-bound RNA in injured naïve cords identify a substantial post-transcriptional regulation gene expression. In particular, transcripts associated with nervous system development were...
Abstract Evidence from previous studies supports the concept that spinal cord injury (SCI)-induced neuropathic pain (NP) has its neural roots in peripheral nervous system. There is uncertainty about how and to which degree mechanoreceptors contribute. Sensorimotor activation-based interventions (eg, treadmill training) have been shown reduce NP after experimental SCI, suggesting transmission of pain-alleviating signals through mechanoreceptors. The aim present study was understand...
Abstract Biomaterial scaffold engineering presents great potential in promoting axonal regrowth after spinal cord injury (SCI), yet persistent challenges remain, including the surrounding host foreign body reaction and improper host-implant integration. Recent advances mechanobiology spark interest optimizing mechanical properties of biomaterial scaffolds to alleviate facilitate seamless The impact stiffness on injured cords has not been thoroughly investigated. Herein, we introduce...