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Inhibition of HMGB1 Attenuates Spinal Cord Edema by Reducing the Expression of Na+-K+-Cl- Cotransporter-1 and Na+/H+ Exchanger-1 in Both Astrocytes and Endothelial Cells After Spinal Cord Injury in Rats

Inhibition of HMGB1 Attenuates Spinal Cord Edema by Reducing the Expression of Na+-K+-Cl- Cotransporter-1 and Na+/H+ Exchanger-1 in Both Astrocytes and Endothelial Cells After Spinal Cord Injury in Rats

Authors :
Li, Man
Lv, Junqiao
Wang, Zhiqiang
Wang, Liping
Qin, Zhixin
Deng, Chen
Liu, Jinming
Sun, Lin
Source :
Journal of Neurotrauma. Dec2023, Vol. 40 Issue 23/24, p2522-2540. 19p.
Publication Year :
2023

Abstract

Sodium/water transport through Na+-K+-Cl- cotransporter-1 (NKCC1) and sodium/hydrogen exchanger-1 (NHE1) in both astrocytes and endothelial cells is critical to cytotoxic and ionic edema following spinal cord injury (SCI). High-mobility group box-1 (HMGB1) promotes spinal cord edema after SCI. Accordingly, we sought to identify both the role of HMGB1 and the mechanism of its effect on NKCC1 and NHE1 expression in astrocytes and endothelial cells as well as the role of the regulation of spinal cord edema after SCI. An SCI model was generated in adult female rats using a heavy falling object, and an in vitro oxygen-glucose deprivation/reoxygenation (OGD/R) model was generated in rat spinal cord astrocytes and microvascular endothelial cells. The inhibition of HMGB1 reduced NKCC1 and NHE1 expression in the spinal cord of SCI rats, in cultured spinal cord astrocytes, and in cultured microvascular endothelial cells. The effects of HMGB1 on NKCC1 and NHE1 expression were mediated—at least in part—by activation of the Toll-like receptor 4 (TLR4)–Toll/interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)–nuclear factor-kappa B (NF-κB) signaling pathway. The inhibition of NKCC1 or NHE1 decreased the spinal cord water content in rats following SCI, increased the Na+ concentration in the medium of cultured astrocytes after OGD/R, and reduced the astrocytic cell volume and AQP4 expression. These results imply that HMGB1 inhibition results in a reduction in NKCC1 and NHE1 expression in both astrocytes and microvascular endothelial cells and thus decreases spinal cord edema after SCI in rats and that these effects occur through the HMGB1–TLR4–TRIF–NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
08977151
Volume :
40
Issue :
23/24
Database :
Academic Search Index
Journal :
Journal of Neurotrauma
Publication Type :
Academic Journal
Accession number :
173989479
Full Text :
https://doi.org/10.1089/neu.2022.0318