@article{ReinholdSchwabeLuxetal.2018,
  author    = {Reinhold, Ann Kristin and Schwabe, Joachim and Lux, Thomas J. and Salvador, Ellaine and Rittner, Heike L.},
  title     = {Quantitative and Microstructural Changes of the Blood-Nerve Barrier in Peripheral Neuropathy},
  series = {Frontiers in Neuroscience},
  volume    = {12},
  journal   = {Frontiers in Neuroscience},
  doi       = {10.3389/fnins.2018.00936},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225179},
  pages     = {936, 1-9},
  year      = {2018},
  abstract  = {Peripheral neuropathy is accompanied by changes in the neuronal environment. The blood-nerve barrier (BNB) is crucial in protecting the neural homeostasis: Tight junctions (TJ) seal paracellular spaces and thus prevent external stimuli from entering. In different models of neuropathic pain, the BNB is impaired, thus contributing to local damage, immune cell invasion and, ultimately, the development of neuropathy with its symptoms. In this study, we examined changes in expression and microstructural localization of two key tight junction proteins (TJP), claudin-1 and the cytoplasmic anchoring ZO-1, in the sciatic nerve of mice subjected to chronic constriction injury (CCI). Via qPCR and analysis of fluorescence immunohistochemistry, a marked downregulation of mRNA as well as decreased fluorescence intensity were observed in the nerve for both proteins. Moreover, a distinct zig-zag structure for both proteins located at cell-cell contacts, indicative of the localization of TJs, was observed in the perineurial compartment of sham-operated animals. This microstructural location in cell-cell-contacts was lost in neuropathy as semiquantified via computational analysis, based on a novel algorithm. In summary, we provide evidence that peripheral neuropathy is not only associated with decrease in relevant TJPs but also exhibits alterations in TJP arrangement and loss in barrier tightness, presumably due to internalization. Specifically, semiquantification of TJP in cell-cell-contacts of microcompartments could be used in the future for routine clinical samples of patients with neuropathy.},
  language  = {en}
}
@phdthesis{Lux2022,
  author    = {Lux, Thomas Joachim},
  title     = {Characterization of Junctional Proteins in the Dorsal Root Ganglion of Rats with Traumatic Nerve Injury},
  doi       = {10.25972/OPUS-25192},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-251926},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2022},
  abstract  = {In my thesis, I characterized aGPCRs Adgrl1 and Adgrl3, tight junction proteins and the blood-DRG-barrier in rats' lumbar dorsal root ganglions after traumatic neuropathy. In contrast to the otherwise tightly sealed barriers shielding neural tissues, the dorsal root ganglion's neuron rich region is highly permeable in its healthy state. Furthermore, the DRG is a source of ectopic signal generation during neuropathy; the exact origin of which is still unclear. I documented expression of Adgrl1 and Adgrl3 in NF200 + , CGRP + and IB4 + neurons. One week after CCI, I observed transient downregulation of Adgrl1 in non-peptidergic nociceptors (IB4+). In the context of previous data, dCirl deletion causing an allodynia-like state in Drosophila, our research hints to a possible role of Adgrl1 nociceptive signal processing and pain resolution in neuropathy. Furthermore, I demonstrated similar claudin-1, claudin-12, claudin-19, and ZO-1 expression of the dorsal root ganglion's neuron rich and fibre rich region. Claudin-5 expression in vessels of the neuron rich region was lower compared to the fibre rich region. Claudin-5 expression was decreased one week after nerve injury in vessels of the neuron rich region while permeability for small and large injected molecules remained unchanged. Nevertheless, we detected more CD68+ cells in the neuron rich region one week after CCI. As clinically relevant conclusion, we verified the high permeability of the neuron rich regions barrier as well as a vessel specific claudin-5 downregulation after CCI. We observed increased macrophage invasion into the neuron rich region after CCI. Furthermore, we identified aGPCR as potential target for further research and possible treatments for neuropathy, which should be easily accessible due to the blood-DRG-barriers leaky nature. Its precise function in peripheral tissues, its mechanisms of activation, and its role in pain resolution should be evaluated further.},
  subject      = {Neuropathy},
  language  = {en}
}