@article{WurmbSchlerethKredeletal.2014, author = {Wurmb, Thomas Erik and Schlereth, Stefan and Kredel, Markus and Muellenbach, Ralf M. and Wunder, Christian and Brederlau, J{\"o}rg and Roewer, Norbert and Kenn, Werner and Kunze, Ekkehard}, title = {Routine Follow-Up Cranial Computed Tomography for Deeply Sedated, Intubated, and Ventilated Multiple Trauma Patients with Suspected Severe Head Injury}, series = {BioMed Research International}, journal = {BioMed Research International}, number = {361949}, doi = {10.1155/2014/361949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120084}, year = {2014}, abstract = {Background. Missed or delayed detection of progressive neuronal damage after traumatic brain injury (TBI) may have negative impact on the outcome. We investigated whether routine follow-up CT is beneficial in sedated and mechanically ventilated trauma patients. Methods. The study design is a retrospective chart review. A routine follow-up cCT was performed 6 hours after the admission scan. We defined 2 groups of patients, group I: patients with equal or recurrent pathologies and group II: patients with new findings or progression of known pathologies. Results. A progression of intracranial injury was found in 63 patients (42\%) and 18 patients (12\%) had new findings in cCT 2 (group II). In group II a change in therapy was found in 44 out of 81 patients (54\%). 55 patients with progression or new findings on the second cCT had no clinical signs of neurological deterioration. Of those 24 patients (44\%) had therapeutic consequences due to the results of the follow-up cCT. Conclusion. We found new diagnosis or progression of intracranial pathology in 54\% of the patients. In 54\% of patients with new findings and progression of pathology, therapy was changed due to the results of follow-up cCT. In trauma patients who are sedated and ventilated for different reasons a routine follow-up CT is beneficial.}, language = {en} } @article{ReinholdKrugSalvadoretal.2022, author = {Reinhold, Ann Kristin and Krug, Susanne M. and Salvador, Ellaine and Sauer, Reine S. and Karl-Sch{\"o}ller, Franziska and Malcangio, Marzia and Sommer, Claudia and Rittner, Heike L.}, title = {MicroRNA-21-5p functions via RECK/MMP9 as a proalgesic regulator of the blood nerve barrier in nerve injury}, series = {Annals of the New York Academy of Sciences}, volume = {1515}, journal = {Annals of the New York Academy of Sciences}, number = {1}, doi = {10.1111/nyas.14816}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318226}, pages = {184 -- 195}, year = {2022}, abstract = {Both nerve injury and complex regional pain syndrome (CRPS) can result in chronic pain. In traumatic neuropathy, the blood nerve barrier (BNB) shielding the nerve is impaired—partly due to dysregulated microRNAs (miRNAs). Upregulation of microRNA-21-5p (miR-21) has previously been documented in neuropathic pain, predominantly due to its proinflammatory features. However, little is known about other functions. Here, we characterized miR-21 in neuropathic pain and its impact on the BNB in a human-murine back translational approach. MiR-21 expression was elevated in plasma of patients with CRPS as well as in nerves of mice after transient and persistent nerve injury. Mice presented with BNB leakage, as well as loss of claudin-1 in both injured and spared nerves. Moreover, the putative miR-21 target RECK was decreased and downstream Mmp9 upregulated, as was Tgfb. In vitro experiments in human epithelial cells confirmed a downregulation of CLDN1 by miR-21 mimics via inhibition of the RECK/MMP9 pathway but not TGFB. Perineurial miR-21 mimic application in mice elicited mechanical hypersensitivity, while local inhibition of miR-21 after nerve injury reversed it. In summary, the data support a novel role for miR-21, independent of prior inflammation, in elicitation of pain and impairment of the BNB via RECK/MMP9.}, language = {en} } @article{SchulteBlum2022, author = {Schulte, Annemarie and Blum, Robert}, title = {Shaped by leaky ER: Homeostatic Ca\(^{2+}\) fluxes}, series = {Frontiers in Physiology}, volume = {13}, journal = {Frontiers in Physiology}, issn = {1664-042X}, doi = {10.3389/fphys.2022.972104}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287102}, year = {2022}, abstract = {At any moment in time, cells coordinate and balance their calcium ion (Ca\(^{2+}\)) fluxes. The term 'Ca\(^{2+}\) homeostasis' suggests that balancing resting Ca2+ levels is a rather static process. However, direct ER Ca\(^{2+}\) imaging shows that resting Ca\(^{2+}\) levels are maintained by surprisingly dynamic Ca\(^{2+}\) fluxes between the ER Ca\(^{2+}\) store, the cytosol, and the extracellular space. The data show that the ER Ca\(^{2+}\) leak, continuously fed by the high-energy consuming SERCA, is a fundamental driver of resting Ca\(^{2+}\) dynamics. Based on simplistic Ca\(^{2+}\) toolkit models, we discuss how the ER Ca\(^{2+}\) leak could contribute to evolutionarily conserved Ca\(^{2+}\) phenomena such as Ca\(^{2+}\) entry, ER Ca\(^{2+}\) release, and Ca\(^{2+}\) oscillations.}, language = {en} } @article{BenKraiemSauerNorwigetal.2021, author = {Ben-Kraiem, Adel and Sauer, Reine-Solange and Norwig, Carla and Popp, Maria and Bettenhausen, Anna-Lena and Atalla, Mariam Sobhy and Brack, Alexander and Blum, Robert and Doppler, Kathrin and Rittner, Heike Lydia}, title = {Selective blood-nerve barrier leakiness with claudin-1 and vessel-associated macrophage loss in diabetic polyneuropathy}, series = {Journal of Molecular Medicine}, volume = {99}, journal = {Journal of Molecular Medicine}, number = {9}, doi = {10.1007/s00109-021-02091-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265237}, pages = {1237-1250}, year = {2021}, abstract = {Diabetic polyneuropathy (DPN) is the most common complication in diabetes and can be painful in up to 26\% of all diabetic patients. Peripheral nerves are shielded by the blood-nerve barrier (BNB) consisting of the perineurium and endoneurial vessels. So far, there are conflicting results regarding the role and function of the BNB in the pathophysiology of DPN. In this study, we analyzed the spatiotemporal tight junction protein profile, barrier permeability, and vessel-associated macrophages in Wistar rats with streptozotocin-induced DPN. In these rats, mechanical hypersensitivity developed after 2 weeks and loss of motor function after 8 weeks, while the BNB and the blood-DRG barrier were leakier for small, but not for large molecules after 8 weeks only. The blood-spinal cord barrier remained sealed throughout the observation period. No gross changes in tight junction protein or cytokine expression were observed in all barriers to blood. However, expression of Cldn1 mRNA in perineurium was specifically downregulated in conjunction with weaker vessel-associated macrophage shielding of the BNB. Our results underline the role of specific tight junction proteins and BNB breakdown in DPN maintenance and differentiate DPN from traumatic nerve injury. Targeting claudins and sealing the BNB could stabilize pain and prevent further nerve damage.}, language = {en} } @article{NotzLotzHerrmannetal.2021, author = {Notz, Quirin and Lotz, Christopher and Herrmann, Johannes and Vogt, Marius and Schlesinger, Tobias and Kredel, Markus and Muellges, Wolfgang and Weismann, Dirk and Westermaier, Thomas and Meybohm, Patrick and Kranke, Peter}, title = {Severe neurological complications in critically ill COVID‑19 patients}, series = {Journal of Neurology}, journal = {Journal of Neurology}, issn = {0340-5354}, doi = {10.1007/s00415-020-10152-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232429}, pages = {1576-1579}, year = {2021}, abstract = {No abstract available.}, language = {en} } @article{HartmannsbergerScribaGuidolinetal.2024, author = {Hartmannsberger, Beate and Scriba, Sabrina and Guidolin, Carolina and Becker, Juliane and Mehling, Katharina and Doppler, Kathrin and Sommer, Claudia and Rittner, Heike L.}, title = {Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome}, series = {Journal of Neuroinflammation}, volume = {21}, journal = {Journal of Neuroinflammation}, doi = {10.1186/s12974-023-02969-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357164}, year = {2024}, abstract = {Background Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed. Methods We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells. Results Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin. Conclusions Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.}, language = {en} } @article{HeckerGruenerHartmannsbergeretal.2023, author = {Hecker, Katharina and Gr{\"u}ner, Julia and Hartmannsberger, Beate and Appeltshauser, Luise and Villmann, Carmen and Sommer, Claudia and Doppler, Kathrin}, title = {Different binding and pathogenic effect of neurofascin and contactin-1 autoantibodies in autoimmune nodopathies}, series = {Frontiers in Immunology}, volume = {14}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2023.1189734}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-320395}, year = {2023}, abstract = {Introduction IgG4 autoantibodies against paranodal proteins are known to induce acute-onset and often severe sensorimotor autoimmune neuropathies. How autoantibodies reach their antigens at the paranode in spite of the myelin barrier is still unclear. Methods We performed in vitro incubation experiments with patient sera on unfixed and unpermeabilized nerve fibers and in vivo intraneural and intrathecal passive transfer of patient IgG to rats, to explore the access of IgG autoantibodies directed against neurofascin-155 and contactin-1 to the paranodes and their pathogenic effect. Results We found that in vitro incubation resulted in weak paranodal binding of anti-contactin-1 autoantibodies whereas anti-neurofascin-155 autoantibodies bound to the nodes more than to the paranodes. After short-term intraneural injection, no nodal or paranodal binding was detectable when using anti-neurofascin-155 antibodies. After repeated intrathecal injections, nodal more than paranodal binding could be detected in animals treated with anti-neurofascin-155, accompanied by sensorimotor neuropathy. In contrast, no paranodal binding was visible in rats intrathecally injected with anti-contactin-1 antibodies, and animals remained unaffected. Conclusion These data support the notion of different pathogenic mechanisms of anti-neurofascin-155 and anti-contactin-1 autoantibodies and different accessibility of paranodal and nodal structures.}, language = {en} } @article{GarciaFernandezHoefflinRauschetal.2023, author = {Garc{\´i}a-Fern{\´a}ndez, Patricia and H{\"o}fflin, Klemens and Rausch, Antonia and Strommer, Katharina and Neumann, Astrid and Cebulla, Nadine and Reinhold, Ann-Kristin and Rittner, Heike and {\"U}{\c{c}}eyler, Nurcan and Sommer, Claudia}, title = {Systemic inflammatory markers in patients with polyneuropathies}, series = {Frontiers in Immunology}, volume = {14}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2023.1067714}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-304217}, year = {2023}, abstract = {Introduction In patients with peripheral neuropathies (PNP), neuropathic pain is present in 50\% of the cases, independent of the etiology. The pathophysiology of pain is poorly understood, and inflammatory processes have been found to be involved in neuro-degeneration, -regeneration and pain. While previous studies have found a local upregulation of inflammatory mediators in patients with PNP, there is a high variability described in the cytokines present systemically in sera and cerebrospinal fluid (CSF). We hypothesized that the development of PNP and neuropathic pain is associated with enhanced systemic inflammation. Methods To test our hypothesis, we performed a comprehensive analysis of the protein, lipid and gene expression of different pro- and anti-inflammatory markers in blood and CSF from patients with PNP and controls. Results While we found differences between PNP and controls in specific cytokines or lipids, such as CCL2 or oleoylcarnitine, PNP patients and controls did not present major differences in systemic inflammatory markers in general. IL-10 and CCL2 levels were related to measures of axonal damage and neuropathic pain. Lastly, we describe a strong interaction between inflammation and neurodegeneration at the nerve roots in a specific subgroup of PNP patients with blood-CSF barrier dysfunction. Conclusion In patients with PNP systemic inflammatory, markers in blood or CSF do not differ from controls in general, but specific cytokines or lipids do. Our findings further highlight the importance of CSF analysis in patients with peripheral neuropathies.}, language = {en} }