Hexahydrocurcumin alleviated blood–brain barrier dysfunction in cerebral ischemia/reperfusion rats
- 1 Downloads
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.
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.
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.
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.
KeywordsBlood–brain barrier Cerebral edema Cerebral ischemia/reperfusion Neutrophil infiltration Tight junction proteins
Bovine serum albumin
Cerebral blood flow
Common carotid artery
Central nervous system
External carotid artery
Hematoxylin and eosin
Internal carotid artery
Middle cerebral artery occlusion and reperfusion
Nuclear factor kappa B
Reactive oxygen species
Transmission electron microscope
Tight junction proteins
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.
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.
- 5.Alluri H, Stagg HW, Wilson RL, Clayton RO, Sawant DA, Koneru M, et al. Reactive oxygen species-caspase-3 relationship in mediating blood–brain barrier endothelial cell hyperpermeability following oxygen–glucose deprivation and reoxygenation. Microcirculation. 2014;21:187–95.PubMedCrossRefGoogle Scholar
- 7.Fukuda AM, Badaut J. Aquaporin 4: a player in cerebral edema and neuroinflammation. J Neuroinflammation. 2012;279:2094–9.Google Scholar
- 13.Gidday JM, Gasche YG, Copin JC, Shah AR, Perez RS, Shapiro SD, et al. Leukocyte-derived matrix metalloproteinase-9 mediates blood–brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am J Physiol Heart Circ Physiol. 2005;289:H558–68.PubMedCrossRefPubMedCentralGoogle Scholar
- 32.Ansari S, Azari H, McConnell DJ, Afzal A, Mocco J. Intraluminal middle cerebral artery occlusion (MCAO) model for ischemic stroke with laser doppler flowmetry guidance in mice. J Vis Exp. 2011;8:2879.Google Scholar