The Influence of Electronic Acupuncture At A Specific Frequency In Facilitating The Passage of NGF Through The Blood-Brain Barrier And Its Effect On Learning And Memory In MCAO/R Rats

Abstract

The blood-brain barrier (BBB) maintains the balance of the internal environment of the brain and strictly controls substance exchange between the brain and blood dynamically but stably. Transient increases in the permeability of the BBB plays an important role in helping macromolecular drugs enter the brain to exert their pharmacological effects. Previous research has revealed that electronic acupuncture (EA) stimulation at a specific frequency can enhance the permeability of the BBB and induce the entry of 20 kDa fluorescein isothiocyanate-dextran (FITC-dextran) into the cerebral cortex, but whether it can also allow drugs to pass the BBB remains unknown. We hypothesized that EA at a specific frequency could open the BBB and induce the entry of nerve growth factor (NGF) into the brain to exert its therapeutic effect. To simulate the clinical apoplexy sequelae observed in patients and determine the basic timing of BBB repair under pathological conditions, we employed the middle cerebral artery occlusion (MCAO) model and assessed changes in the permeability and structure of the BBB by measuring both the intensity of Evans blue (EB) staining and the cerebral infarction volume and evaluating the ultrastructure of the BBB. Then, we used a laser spectrometer and immunofluorescence to observe entry of NGF into the brain. Finally, we assessed the learning and memory ability of rats and used the DeadEnd TM Fluorometric TUNEL System to assess apoptosis in the hippocampus. Our results showed that the BBB was essentially repaired three weeks after MCAO, indicating that EA stimulation at a specific frequency can enhance BBB permeability and induce NGF uptake by prefrontal neurons. In the presence of EA stimulation, entry of NGF into the brain promoted learning and memory in rats and inhibited the apoptosis of neurons in the hippocampus. In this study, the MCAO model was used to determine the timing of BBB repair under pathological conditions and assess the EA stimulation-induced entry of NGF into the brain to exert its therapeutic effect. EA could serve as a new strategy for delivering therapeutics to the central nervous system (CNS), given that EA stimulation at a specific frequency was shown to increase the permeability of the BBB. Further study of the mechanism underlying the opening of the BBB and its timing is needed.

The factors affecting neurogenesis after stroke and the role of acupuncture

“…It was also found that EA at GV20 and Shuigou (GV26) enhanced the permeability of the blood-brain barrier in the prefrontal cortex and induced the uptake of NGF by prefrontal neurons (156). Nape cluster acupuncture has neuroprotective and restorative effects in rats with post-ischemic stroke sequelae, and its mechanism may involve effective upregulation of BDNF and NGF protein expression (157).…”

Acupuncture Interventions for Alzheimer’s Disease and Vascular Cognitive Disorders: A Review of Mechanisms

“…A fixed frequency of 2 or 100 Hz may show easy adaptability and a relatively continuous and stable stimulation, which may reduce the effect of EA [143]. Therefore, 2/100 Hz EA was applied to the GV20 and GV26 acupoints for 40 min, effectively increasing BBB permeability in rats [144]. However, for hippocampal synaptic transmission, high-frequency EA could demonstrate a better effect in rats with Alzheimer's disease [145].…”

“…Acupuncture can upregulate vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), basic fibroblast growth factor (bFGF), and CD34 + , thereby promoting the proliferation of vascular endothelial cells, increasing local cerebral blood flow, activating multiple signaling pathways, and mediating vascular and nerve regeneration [158]. EA stimulation of "Baihui" (GV20) and "Shuigou" (GV26) at a specific frequency has been reported to increase the permeability of BBB, providing a strategy for the treatment Oxidative Medicine and Cellular Longevity of nervous system diseases [143,144]. Liu et al [111] found that EA could regulate the expression of VEGF genes and promote angiogenesis in the ischemic cerebral cortex, which may play an important role in the improvement of CI in ischemic stroke.…”