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Hexahydrocurcumin alleviated blood–brain barrier dysfunction in cerebral ischemia/reperfusion rats

  • Piyawadee Wicha
  • Jiraporn Tocharus
  • Adchara Janyou
  • Jinatta Jittiwat
  • Waraluck Chaichompoo
  • Apichart Suksamrarn
  • Chainarong TocharusEmail author
Article
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Abstract

Background

Hexahydrocurcumin (HHC), a major metabolite of curcumin, has been reported to have protective effects against ischemic and reperfusion damage. The goal of the present research was to examine whether HHC could alleviate brain damage and ameliorate functional outcomes by diminishing the blood–brain barrier (BBB) damage that follows cerebral ischemia/reperfusion.

Methods

Middle cerebral artery occlusion was induced for 2 h in rats followed by reperfusion. The rats were divided into three groups: sham-operated, vehicle-treated, and HHC-treated groups. At the onset of reperfusion, the rats were immediately intraperitoneally injected with 40 mg/kg HHC. At 48 h after reperfusion, the rats were evaluated for neurological deficits and TTC staining. At 24 h and 48 h after reperfusion, animals were sacrificed, and their brains were extracted.

Results

Treatment with HHC reduced neurological scores, infarct volume, morphological changes, Evans blue leakage and immunoglobulin G extravasation. Moreover, HHC treatment reduced BBB damage and neutrophil infiltration, downregulated myeloperoxidase, ICAM-1, and VCAM-1, upregulated tight junction proteins (TJPs), and reduced aquaporin 4 expression and brain water content.

Conclusion

These results revealed that HHC treatment preserved the BBB from cerebral ischemia/reperfusion injury by regulating TJPs, attenuating neutrophil infiltration, and reducing brain edema formation.

Graphic abstract

Keywords

Blood–brain barrier Cerebral edema Cerebral ischemia/reperfusion Neutrophil infiltration Tight junction proteins 

Abbreviations

AQP4

Aquaporin 4

AS

Astrocytic swelling

BBB

Blood–brain barrier

BM

Basement membrane

BSA

Bovine serum albumin

CBF

Cerebral blood flow

CCA

Common carotid artery

CNS

Central nervous system

COX-2

Cyclooxygenase-2

EB

Evans blue

ECA

External carotid artery

ECM

Extracellular matrix

GI

Gastrointestinal

H&E

Hematoxylin and eosin

HHC

Hexahydrocurcumin

HRP

Horseradish peroxidase

I/R

Ischemia reperfusion

ICA

Internal carotid artery

IgG

Immunoglobulin G

MCAO/R

Middle cerebral artery occlusion and reperfusion

MMPs

Matrix metalloproteases

MPO

Myeloperoxidase

NF-κB

Nuclear factor kappa B

PVDF

Polyvinylidene fluoride

ROS

Reactive oxygen species

TEM

Transmission electron microscope

TJPs

Tight junction proteins

TTC

2,3,5-Triphenyltetrazolium chloride

ZO-1

Zona occludens-1

Notes

Acknowledgements

This study was supported by Functional Food Research Center for Well-being, Chiang Mai University and Faculty of Medicine Chiang Mai University. We also gratefully acknowledge support from the Thailand Research Fund (DBG6180030) and the Center of Excellence for Innovation in Chemistry, Office of the Higher Education Commission. PW acknowledges the financial support of the Royal Golden Jubilee (RGJ) PhD program (Grant No. PHD/0008/2558). We thank the staff of the Medical Science Research Equipment Center, Faculty of Medicine, Chiang Mai University for their help in the preparation of the tissue to be analyzed by Transmission Electron Microscopy.

Authors’ contribution

Conception: CT. Data curation: PW, JT, and CT. Funding acquisition: AS, CT. Methodology: PW, JT, AJ, JJ, and WC. Project administration: CT. Resources: AS. Supervision: CT. Writing—original draft: PW. Writing—review and editing: AS and CT.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Maj Institute of Pharmacology Polish Academy of Sciences 2020

Authors and Affiliations

  • Piyawadee Wicha
    • 1
  • Jiraporn Tocharus
    • 2
  • Adchara Janyou
    • 1
  • Jinatta Jittiwat
    • 3
  • Waraluck Chaichompoo
    • 4
  • Apichart Suksamrarn
    • 4
  • Chainarong Tocharus
    • 1
    Email author
  1. 1.Department of Anatomy, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  2. 2.Department of Physiology, Faculty of MedicineChiang Mai UniversityChiang MaiThailand
  3. 3.Faculty of MedicineMaha Sarakham UniversityMaha SarakhamThailand
  4. 4.Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of ScienceRamkhamhaeng UniversityBangkokThailand

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