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.
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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
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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.
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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.
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Wicha, P., Tocharus, J., Janyou, A. et al. Hexahydrocurcumin alleviated blood–brain barrier dysfunction in cerebral ischemia/reperfusion rats. Pharmacol. Rep 72, 659–671 (2020). https://doi.org/10.1007/s43440-019-00050-9
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DOI: https://doi.org/10.1007/s43440-019-00050-9