Your browser doesn't support javascript.
loading
Induced Inflammatory and Oxidative Markers in Cerebral Microvasculature by Mentally Depressive Stress.
Zhu, Yuequan; Haddad, Yazeed; Yun, Ho Jun; Geng, Xiaokun; Ding, Yuchuan.
Afiliação
  • Zhu Y; China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China.
  • Haddad Y; Department of Neurosurgery, Wayne State University School of Medicine, USA.
  • Yun HJ; Department of Neurosurgery, Wayne State University School of Medicine, USA.
  • Geng X; China-America Institute of Neuroscience, Beijing Luhe Hospital, Capital Medical University, China.
  • Ding Y; Department of Neurosurgery, Wayne State University School of Medicine, USA.
Mediators Inflamm ; 2023: 4206316, 2023.
Article em En | MEDLINE | ID: mdl-36852396
ABSTRACT

Background:

Cerebrovascular disease (CVD) is recognized as the leading cause of permanent disability worldwide. Depressive disorders are associated with increased incidence of CVD. The goal of this study was to establish a chronic restraint stress (CRS) model for mice and examine the effect of stress on cerebrovascular inflammation and oxidative stress responses.

Methods:

A total of forty 6-week-old male C57BL/6J mice were randomly divided into the CRS and control groups. In the CRS group (n = 20), mice were placed in a well-ventilated Plexiglas tube for 6 hours per day for 28 consecutive days. On day 29, open field tests (OFT) and sucrose preference tests (SPT) were performed to assess depressive-like behaviors for the two groups (n = 10/group). Macrophage infiltration into the brain tissue upon stress was analyzed by measuring expression of macrophage marker (CD68) with immunofluorescence in both the CRS and control groups (n = 10/group). Cerebral microvasculature was isolated from the CRS and controls (n = 10/group). mRNA and protein expressions of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1), and macrophage chemoattractant protein-1 (MCP-1) in the brain vessels were measured by real-time PCR and Western blot (n = 10/group). Reactive oxygen species (ROS), hydrogen peroxide (H2O2), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) activities were quantified by ELISA to study the oxidative profile of the brain vessels (n = 10/group). Additionally, mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in the cerebrovascular endothelium were analyzed by real-time PCR and Western blot (n = 10/group).

Results:

CRS decreased the total distances (p < 0.05) and the time spent in the center zone in OFT (p < 0.001) and sucrose preference test ratio in SPT (p < 0.01). Positive ratio of CD68+ was increased with CRS in the entire region of the brain (p < 0.001), reflecting increased macrophage infiltration. CRS increased the expression of inflammatory factors and oxidative stress in the cerebral microvasculature, including TNF-α (p < 0.001), IL-1ß (p < 0.05), IL-6 (p < 0.05), VCAM-1 (p < 0.01), MCP-1 (p < 0.01), ROS (p < 0.001), and H2O2 (p < 0.001). NADPH oxidase (NOX) was activated by CRS (p < 0.01), and mRNA and protein expressions of NOX subunits (gp91phox, p47phox, p67phox, and p22phox) in brain microvasculature were found to be increased.

Conclusions:

To our knowledge, this is the first study to demonstrate that CRS induces depressive stress and causes inflammatory and oxidative stress responses in the brain microvasculature.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Cardiovasculares / Peróxido de Hidrogênio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Cardiovasculares / Peróxido de Hidrogênio Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article