Electroacupuncture on trigeminal nerve innervated acupoints ameliorates cognitive impairment induced by ischemia and chemotherapy in animal models : associations with modulation of microglia-derived cytokines and neuroplasticity

Abstract

Cognitive impairment (CI) means people have problems with cognitive functions such as thinking, reasoning, memory, or attention. These deficits can harm daily quality of life. CI has several risk factors, some of which are reversible. This project considered two kinds of CI – the well-known vascular cognitive impairment (VCI) and the much less studied chemotherapy-induced cognitive impairment (CICI) – with the aim of further exploring the potential for acupuncture as a treatment approach for CI patients.

Acupuncture has been gradually introduced for neurodegeneration disorders. Electroacupuncture (EA) is a treatment that applies weak electricity through acupuncture needles, giving the patients acupuncture and electrical stimulation simultaneously. Many clinical studies have shown that acupuncture/EA is valuable in improving the cognitive function in CI patients. Meanwhile, animal experiments have also illustrated the rationale of using acupuncture in CI treatment. In this study, EA was conducted on the two scalp acupoints, Yintang (EX- HN3) and Baihui (GV20), innervated by the trigeminal nerve in animal models to explore the use of EA with VCI and CICI.

In Study #1, a classical animal stroke model (middle cerebral artery occlusion, MCAO) was adopted as the VCI model. Behavior tests were conducted to evaluate cognitive function. In the water maze test, the model animal took more time to reach the platform during the training days and spent less time in the targeted quadrant in the probe test. A lower discrimination index to the novel object in the model group was found in the novel object recognition test. During the whole experiment period, there was no difference in the time spent in the central zone in the open field test. However, EA treatment could reverse these cognitive declines. Moreover, EA protected against ischemia/reperfusion-induced cognitive declines in the neurotrophin, neurotransmitter receptors, and neuroplasticity biomarkers expressions in the hippocampus and prefrontal cortex.

In Study #2, the CICI mouse model was established with a chemotherapy reagents mixture (docetaxel, adriamycin, and cyclophosphamide, DAC) at every two days in one week. The model animal also showed cognitive impairment, but no anxiety level or locomotor activity changes in the above-mentioned behavior tests. In addition to the similar western blot results found in Study #1, neuroinflammation-related cytokines were also detected. DAC induced a marked enhancement in IL-6 and TNF-α expression and reduction in Arg-1 expression in the hippocampus and prefrontal cortex. Cytokine dysfunction amelioration and a switch of the microglia phenotype were found in the EA treatment group.

To sum up, EA at the Yintang (EX- HN3) and Baihui (GV20) acupoints could improve cognitive impairment in the MCAO and CICI models by regulating cytokine expression and synaptic plasticity in specific brain regions. Although the pathogenesis of VCI and CICI are different in both clinical and animal models, EA could ameliorate the cognitive function impairment in both animal experiments. In traditional Chinese medicine theory, this is called treating different diseases with the same method (異病同治).