Hexahydrocurcumin protect myelin damage in Alzheimer’s disease ‐like pathology in bilateral common carotid artery occlusion

Abstract Background Age‐related dementia is usually found in the condition of chronic cerebral hypoperfusion (CCH) by altering the regional cerebral blood flow (rCBF) that causes neuronal damage. The white matter and hippocampal areas are the regions sensitive to CBF lowering which can change that local metabolic stress, initiate inflammatory processes and thereby neuronal cell injury that become the cognitive impairment. Method Male rats underwent with the bilateral common carotid artery occlusion (BCCAO) for 28 days, were divided into 3 groups; (1) sham group: sham operated + 0.1% hydroxyl cellulose; (2) BCCAO group: BCCAO operated + 0.1% hydroxyl cellulose; (3) HHC group: BCCAO operated + HHC 40 mg/kg. All rats were evaluated memory impairment by the Morris water maze test, then the brain tissues were investigated the protein expression by Western blotting analysis (APOE, IL‐1β, TNFα, MBP, p‐Tau), determined Aβ 40‐42 levels by ELISA kit, and myelin integrity via TEM. Result The BCCAO group significantly decreased time in the target quadrant as it represented cognitive impairment, increased pro‐inflammatory cytokines, loss of myelin basic protein and myelin integrity compared to the control group. Moreover, BCCAO upregulated Alzheimer’s disease (AD) markers including p‐Tau and the levels of Aβ 40‐42 . On the other hand, hexahydrocurcumin (HHC) treatment group significantly attenuated cognitive deficit, pro‐inflammatory cytokines released, and myelin integrity compared to BCCAO group. Furthermore, HHC also mitigated AD markers by decreasing p‐Tau and Aβ 40‐42 levels. Conclusion The CCH induction by the model of bilateral common carotid artery occlusion (BCCAO) 28 days shows the cognitive impairment, inflammatory burst, and white matter injury. Moreover, BCCAO is able to accelerate AD markers. However, HHC treatment protects cognitive deficit and white matter injury drive AD by inhibiting inflammatory responses.