TY  - JOUR
A1  - Lux, Thomas J.
A1  - Hu, Xiawei
A1  - Ben-Kraiem, Adel
A1  - Blum, Robert
A1  - Chen, Jeremy Tsung-Chieh
A1  - Rittner, Heike L.
T1  - Regional differences in tight junction protein expression in the blood−DRG barrier and their alterations after nerve traumatic injury in rats
JF  - International Journal of Molecular Sciences
N2  - The nervous system is shielded by special barriers. Nerve injury results in blood–nerve barrier breakdown with downregulation of certain tight junction proteins accompanying the painful neuropathic phenotype. The dorsal root ganglion (DRG) consists of a neuron-rich region (NRR, somata of somatosensory and nociceptive neurons) and a fibre-rich region (FRR), and their putative epi-/perineurium (EPN). Here, we analysed blood–DRG barrier (BDB) properties in these physiologically distinct regions in Wistar rats after chronic constriction injury (CCI). Cldn5, Cldn12, and Tjp1 (rats) mRNA were downregulated 1 week after traumatic nerve injury. Claudin-1 immunoreactivity (IR) found in the EPN, claudin-19-IR in the FRR, and ZO-1-IR in FRR-EPN were unaltered after CCI. However, laser-assisted, vessel specific qPCR, and IR studies confirmed a significant loss of claudin-5 in the NRR. The NRR was three-times more permeable compared to the FRR for high and low molecular weight markers. NRR permeability was not further increased 1-week after CCI, but significantly more CD68\(^+\) macrophages had migrated into the NRR. In summary, NRR and FRR are different in naïve rats. Short-term traumatic nerve injury leaves the already highly permeable BDB in the NRR unaltered for small and large molecules. Claudin-5 is downregulated in the NRR. This could facilitate macrophage invasion, and thereby neuronal sensitisation and hyperalgesia. Targeting the stabilisation of claudin-5 in microvessels and the BDB barrier could be a future approach for neuropathic pain therapy.
KW  - tight junction
KW  - claudin-5
KW  - neuropathic pain
KW  - nerve injury
KW  - dorsal root ganglion
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285029
SN  - 1422-0067
VL  - 21
IS  - 1
ER  - 
TY  - JOUR
A1  - Jende, Johann M. E.
A1  - Kender, Zoltan
A1  - Rother, Christian
A1  - Alvarez-Ramos, Lucia
A1  - Groener, Jan B.
A1  - Pham, Mirko
A1  - Morgenstern, Jakob
A1  - Oikonomou, Dimitrios
A1  - Hahn, Artur
A1  - Juerchott, Alexander
A1  - Kollmer, Jennifer
A1  - Heiland, Sabine
A1  - Kopf, Stefan
A1  - Nawroth, Peter P.
A1  - Bendszus, Martin
A1  - Kurz, Felix T.
T1  - Diabetic Polyneuropathy Is Associated With Pathomorphological Changes in Human Dorsal Root Ganglia: A Study Using 3T MR Neurography
JF  - Frontiers in Neuroscience
N2  - Diabetic neuropathy (DPN) is one of the most severe and yet most poorly understood complications of diabetes mellitus. In vivo imaging of dorsal root ganglia (DRG), a key structure for the understanding of DPN, has been restricted to animal studies. These have shown a correlation of decreased DRG volume with neuropathic symptom severity. Our objective was to investigate correlations of DRG morphology and signal characteristics at 3 Tesla (3T) magnetic resonance neurography (MRN) with clinical and serological data in diabetic patients with and without DPN. In this cross-sectional study, participants underwent 3T MRN of both L5 DRG using an isotropic 3D T2-weighted, fat-suppressed sequence with subsequent segmentation of DRG volume and analysis of normalized signal properties. Overall, 55 diabetes patients (66 ± 9 years; 32 men; 30 with DPN) took part in this study. DRG volume was smaller in patients with severe DPN when compared to patients with mild or moderate DPN (134.7 ± 21.86 vs 170.1 ± 49.22; p = 0.040). In DPN patients, DRG volume was negatively correlated with the neuropathy disability score (r = −0.43; 95%CI = −0.66 to −0.14; p = 0.02), a measure of neuropathy severity. DRG volume showed negative correlations with triglycerides (r = −0.40; 95%CI = −0.57 to −0.19; p = 0.006), and LDL cholesterol (r = −0.33; 95%CI = −0.51 to −0.11; p = 0.04). There was a strong positive correlation of normalized MR signal intensity (SI) with the neuropathy symptom score in the subgroup of patients with painful DPN (r = 0.80; 95%CI = 0.46 to 0.93; p = 0.005). DRG SI was positively correlated with HbA1c levels (r = 0.30; 95%CI = 0.09 to 0.50; p = 0.03) and the triglyceride/HDL ratio (r = 0.40; 95%CI = 0.19 to 0.57; p = 0.007). In this first in vivo study, we found DRG morphological degeneration and signal increase in correlation with neuropathy severity. This elucidates the potential importance of MR-based DRG assessments in studying structural and functional changes in DPN.
KW  - diabetic polyneuropathy
KW  - dorsal root ganglion
KW  - magnetic resonance neurography
KW  - neuropathic pain
KW  - peripheral nervous system
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212459
VL  - 14
ER  -