Simvastatin attenuates sepsis-induced blood-brain barrier integrity loss

Chen Hsien Yang, Ming Chan Kao, Ping Cheng Shih, Kuang Yao Li, Pei Shan Tsai, Chun Jen Huang

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background Systemic inflammation and oxidative stress are crucial in mediating blood-brain barrier (BBB) integrity loss during sepsis. Simvastatin possess potent anti-inflammation and antioxidation capacity. We sought to elucidate whether an acute bolus of simvastatin could mitigate BBB integrity loss in a rodent model of polymicrobial sepsis. Methods A total of 96 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus simvastatin, sham operation, or sham operation plus simvastatin (n = 24 in each group). After maintaining for 24 h, BBB integrity in the surviving rats was determined. Results CLP significantly induced BBB integrity loss, as grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels in rats receiving CLP were significantly higher than those receiving sham operation. In contrast, grading of Evans blue staining (P = 0.020), BBB permeability to Evans blue dye (P = 0.031), and brain edema levels (P = 0.009) in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP alone. Tight junction proteins claudin-3 and claudin-5 in endothelial cells are major structural components of BBB. Our data revealed that concentrations of claudin-3 and claudin-5 in rats receiving CLP were significantly lower than those receiving CLP plus simvastatin (P = 0.010 and 0.007). Immunohistochemistry further revealed significant fragmentation of claudin-3 and claudin-5 in rats receiving CLP. Moreover, levels of claudin-3 and claudin-5 fragmentation in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP. Conclusions Simvastatin mitigates BBB integrity loss in a rodent model of polymicrobial sepsis.

Original languageEnglish
Pages (from-to)591-598
Number of pages8
JournalJournal of Surgical Research
Volume194
Issue number2
DOIs
Publication statusPublished - Apr 1 2015

Fingerprint

Simvastatin
Blood-Brain Barrier
Punctures
Ligation
Sepsis
Claudin-3
Claudin-5
Evans Blue
Brain Edema
Rodentia
Permeability
Coloring Agents
Staining and Labeling
Inflammation
Tight Junction Proteins
Oxidative Stress
Endothelial Cells
Immunohistochemistry

Keywords

  • Cecal ligation and puncture
  • Evans blue dye
  • Inflammation
  • Rat
  • Tight junction

ASJC Scopus subject areas

  • Surgery

Cite this

Simvastatin attenuates sepsis-induced blood-brain barrier integrity loss. / Yang, Chen Hsien; Kao, Ming Chan; Shih, Ping Cheng; Li, Kuang Yao; Tsai, Pei Shan; Huang, Chun Jen.

In: Journal of Surgical Research, Vol. 194, No. 2, 01.04.2015, p. 591-598.

Research output: Contribution to journalArticle

Yang, Chen Hsien ; Kao, Ming Chan ; Shih, Ping Cheng ; Li, Kuang Yao ; Tsai, Pei Shan ; Huang, Chun Jen. / Simvastatin attenuates sepsis-induced blood-brain barrier integrity loss. In: Journal of Surgical Research. 2015 ; Vol. 194, No. 2. pp. 591-598.
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abstract = "Background Systemic inflammation and oxidative stress are crucial in mediating blood-brain barrier (BBB) integrity loss during sepsis. Simvastatin possess potent anti-inflammation and antioxidation capacity. We sought to elucidate whether an acute bolus of simvastatin could mitigate BBB integrity loss in a rodent model of polymicrobial sepsis. Methods A total of 96 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus simvastatin, sham operation, or sham operation plus simvastatin (n = 24 in each group). After maintaining for 24 h, BBB integrity in the surviving rats was determined. Results CLP significantly induced BBB integrity loss, as grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels in rats receiving CLP were significantly higher than those receiving sham operation. In contrast, grading of Evans blue staining (P = 0.020), BBB permeability to Evans blue dye (P = 0.031), and brain edema levels (P = 0.009) in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP alone. Tight junction proteins claudin-3 and claudin-5 in endothelial cells are major structural components of BBB. Our data revealed that concentrations of claudin-3 and claudin-5 in rats receiving CLP were significantly lower than those receiving CLP plus simvastatin (P = 0.010 and 0.007). Immunohistochemistry further revealed significant fragmentation of claudin-3 and claudin-5 in rats receiving CLP. Moreover, levels of claudin-3 and claudin-5 fragmentation in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP. Conclusions Simvastatin mitigates BBB integrity loss in a rodent model of polymicrobial sepsis.",
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AU - Tsai, Pei Shan

AU - Huang, Chun Jen

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N2 - Background Systemic inflammation and oxidative stress are crucial in mediating blood-brain barrier (BBB) integrity loss during sepsis. Simvastatin possess potent anti-inflammation and antioxidation capacity. We sought to elucidate whether an acute bolus of simvastatin could mitigate BBB integrity loss in a rodent model of polymicrobial sepsis. Methods A total of 96 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus simvastatin, sham operation, or sham operation plus simvastatin (n = 24 in each group). After maintaining for 24 h, BBB integrity in the surviving rats was determined. Results CLP significantly induced BBB integrity loss, as grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels in rats receiving CLP were significantly higher than those receiving sham operation. In contrast, grading of Evans blue staining (P = 0.020), BBB permeability to Evans blue dye (P = 0.031), and brain edema levels (P = 0.009) in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP alone. Tight junction proteins claudin-3 and claudin-5 in endothelial cells are major structural components of BBB. Our data revealed that concentrations of claudin-3 and claudin-5 in rats receiving CLP were significantly lower than those receiving CLP plus simvastatin (P = 0.010 and 0.007). Immunohistochemistry further revealed significant fragmentation of claudin-3 and claudin-5 in rats receiving CLP. Moreover, levels of claudin-3 and claudin-5 fragmentation in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP. Conclusions Simvastatin mitigates BBB integrity loss in a rodent model of polymicrobial sepsis.

AB - Background Systemic inflammation and oxidative stress are crucial in mediating blood-brain barrier (BBB) integrity loss during sepsis. Simvastatin possess potent anti-inflammation and antioxidation capacity. We sought to elucidate whether an acute bolus of simvastatin could mitigate BBB integrity loss in a rodent model of polymicrobial sepsis. Methods A total of 96 adult male rats (200-250 g) were randomized to receive cecal ligation and puncture (CLP), CLP plus simvastatin, sham operation, or sham operation plus simvastatin (n = 24 in each group). After maintaining for 24 h, BBB integrity in the surviving rats was determined. Results CLP significantly induced BBB integrity loss, as grading of Evans blue staining of the brains, BBB permeability to Evans blue dye, and brain edema levels in rats receiving CLP were significantly higher than those receiving sham operation. In contrast, grading of Evans blue staining (P = 0.020), BBB permeability to Evans blue dye (P = 0.031), and brain edema levels (P = 0.009) in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP alone. Tight junction proteins claudin-3 and claudin-5 in endothelial cells are major structural components of BBB. Our data revealed that concentrations of claudin-3 and claudin-5 in rats receiving CLP were significantly lower than those receiving CLP plus simvastatin (P = 0.010 and 0.007). Immunohistochemistry further revealed significant fragmentation of claudin-3 and claudin-5 in rats receiving CLP. Moreover, levels of claudin-3 and claudin-5 fragmentation in rats receiving CLP plus simvastatin were significantly lower than those receiving CLP. Conclusions Simvastatin mitigates BBB integrity loss in a rodent model of polymicrobial sepsis.

KW - Cecal ligation and puncture

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KW - Inflammation

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KW - Tight junction

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