Electroacupuncture Efficacy Evaluation on Blood-Brain Barrier and Cerebral Blood FlowFunction in SAMP8 Mice

Insufficient cerebral blood flow plays a pivotal role in neuropathology in humans and animals, producing Alzheimer's disease (AD) like symptoms.Blood brain barrier (BBB) dysfunction may be one of the potential causes of insufficient cerebral blood supply, leading to these problems.Electroacupuncture (EA) can show promise in improving cognitive abilities and CNS functions.However, its effects on cerebral blood flow and the blood-brain barrier are not yet clear.SAMP8 mice were randomly assigned to three experimental groups: the Alzheimer's disease model (AD), electro-acupuncture intervention (EA), and donepezil treatment (D) groups.SAMP8 mice received EA at GV20/GV29 (2 mA, 100/2 Hz) in the EA group or donepezil (1mg/kg) in the D group for 21 days.SAMR1 mice serve as optimal controls for SAMP8 in AD research due to their genetic congruence and age-matched normal aging profile, which effectively isolate AD-specific pathologies by eliminating non-AD-related aging confounders, it worked as the normal (N) controls.Morri's water maze observed the behavioral changes of mice in all groups, the blood flow perfusion in the cortical area of the cerebrum was observed by the RFLSI ZW laser speckle imaging system, and the integrity of the basement membrane and tight junctions of the BBB were observed by transmission electron microscope.Nissl and Hematoxylin and eosin staining observed the morphological changes of nerve cells in the hippocampal region.Cytokine and protein expression levels were determined by Enzyme-Linked Immunosorbent Assay or western blotting.Compared with the N group, cognitive ability and cerebral blood flow were significantly decreased, the function and integrity of BBB were disrupted, the neuronal structure was heavily damaged, and the serum and brain inflammatory responses were increased in mice of the AD group (P<0.01).All of these pathologies were recovered by the EA group and D group (P<0.05/P<0.01).Although the positive control drug donepezil partially ameliorated cognitive deficits, cerebral blood flow (CBF), and neuropathological damage in SAMP8 mice, EA uniquely restored CBF to control levels and exhibited stronger antiinflammatory effects than donepezil.The results of this study show that EA improves the cognitive ability of mice and alleviates central neuronal damage.This protective effect might be attributed to EA's dual mechanisms of enhancing cerebral perfusion and suppressing inflammatory pathways, mediated through MMp-9 and ICAM-1inhibition, which collectively restore blood-brain barrier integrity and mitigate barrier damage.