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Open AccessArticle

Regional Differences in Tight Junction Protein Expression in the Blood–DRG Barrier and Their Alterations after Nerve Traumatic Injury in Rats

1
Department of Anaesthesiology, University Hospital of Wuerzburg, 97074 Wuerzburg, Germany
2
Institute of Clinical Neurobiology, University Hospital of Wuerzburg, 94074 Wuerzburg, Germany
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(1), 270; https://doi.org/10.3390/ijms21010270
Received: 9 December 2019 / Revised: 23 December 2019 / Accepted: 28 December 2019 / Published: 31 December 2019
(This article belongs to the Special Issue The Tight Junction and Its Proteins: More Than Just a Barrier)
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. View Full-Text
Keywords: tight junction; claudin-5; neuropathic pain; nerve injury; dorsal root ganglion tight junction; claudin-5; neuropathic pain; nerve injury; dorsal root ganglion
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Lux, T.J.; Hu, X.; Ben-Kraiem, A.; Blum, R.; Chen, J. .-C.; Rittner, H.L. Regional Differences in Tight Junction Protein Expression in the Blood–DRG Barrier and Their Alterations after Nerve Traumatic Injury in Rats. Int. J. Mol. Sci. 2020, 21, 270.

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