Hyperglycemia disrupted the integrity of the blood-brain barrier following diffuse axonal injury through the sEH/NF-κB pathway.

Publisher: John Wiley and Sons Ltd Country of Publication: England NLM ID: 101635460 Publication Model: Print Cited Medium: Internet ISSN: 2050-4527 (Electronic) Linking ISSN: 20504527 NLM ISO Abbreviation: Immun Inflamm Dis Subsets: MEDLINE

Original Publication: [Oxford] : John Wiley and Sons Ltd, [2013]-

Diffuse Axonal Injury* ; Hyperglycemia*; Animals ; Rats ; Blood-Brain Barrier ; Epoxide Hydrolases/metabolism ; NF-kappa B/metabolism ; Tight Junction Proteins/metabolism

Objectives: We aimed to investigate the role of soluble epoxide hydrolase for hyperglycemia induced-disruption of blood-brain barrier (BBB) integrity after diffuse axonal injury (DAI).
Methods: Rat DAI hyperglycemia model was established by a lateral head rotation device and intraperitoneal injection of 50% glucose. Glial fibrillary acidic protein, ionized calcium-binding adapter molecule-1, β-amyloid precursor protein, neurofilament light chain, and neurofilament heavy chain was detected by immunohistochemistry. Cell apoptosis was examined by terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) assay. The permeability of blood-brain barrier (BBB) was assessed by expression of tight junction proteins, leakage of Evans blue and brain water content. The soluble epoxide hydrolase (sEH) pathway was inhibited by 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the nuclear transcription factor kappa B (NF-κB) pathway was inhibited by pyrrolidine dithiocarbamate and activated by phorbol-12-myristate-13-acetate in vivo and/or vitro, respectively. The inflammatory factors were detected by enzyme-linked immunosorbent assay.
Results: Hyperglycemia could exacerbate axonal injury, aggravate cell apoptosis and glial activation, worsen the loss of BBB integrity, increase the release of inflammatory factors, and upregulate the expression of sEH and NF-κB. Inhibition of sEH could reverse all these damages and protect BBB integrity by upregulating the expression of tight junction proteins and downregulating the levels of inflammatory factors in vivo and vitro, while the agonist of NF-κB pathway abrogated the protective effects of TPPU on BBB integrity in vitro.
Conclusions: sEH was involved in mediating axonal injury induced by hyperglycemia after DAI by disrupting BBB integrity through inducing inflammation via the NF-κB pathway.
(© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

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82001327 National Natural Science Foundation of China

Keywords: diffuse axonal injury; hyperglycemia; nuclear transcription factor kappa B; soluble epoxide hydrolase

EC 3.3.2.- (Epoxide Hydrolases)
0 (NF-kappa B)
0 (Tight Junction Proteins)

Date Created: 20231229 Date Completed: 20240102 Latest Revision: 20240102

20240103

PMC10698817

10.1002/iid3.1105

38156378