Acupuncture Can Regulate the Peripheral Immune Cell Spectrum and Inflammatory Environment of the Vascular Dementia Rat, and Improve the Cognitive Dysfunction of the Rats.

Pan Pan,Zhen Zhang,Xuezhu Zhang,Qiuping Liu,Pan Xu,Xiaolin Lin,Runmin Wang,Hui Zhi,Zhinan Ma,Dan Yang,Yao Wang,Zhenzhen Ling

doi:10.3389/fnagi.2021.706834

Abstract

ObjectiveThe aim of this study is to analyze the effects of acupuncture on peripheral immune function, inflammation, and cognitive impairment in vascular dementia (VD) rats.MethodsIn this study, 2-month-old healthy male Wistar rats (260–280 g) were assigned to the groups as follows: normal group (Gn, n = 10), sham-operated group (Gs, n = 10), and operated group (Go, n = 45). The Go group was established by permanent, bilateral common carotid artery occlusion (BCCAO). Two months after operation, the operated rats were screened by hidden platform trial and the rats with cognitive dysfunction were further randomly divided into impaired group (Gi), acupoint group (Ga), and non-acupoint group (Gna) with 10 rats in each group. The Ga group was given acupuncture treatment for 14 days with a rest for every 7 days. After treatment, the Morris water maze (MWM) test was performed to evaluate the spatial learning and memory abilities of rats. The lymphocyte subsets in peripheral blood and spleen of rats were measured by flow cytometry. The levels of cytokines [i.e., interleukin (IL)-1β, IL-2, IL-4, IL-10, tumor necrosis factor-α (TNF-α), and interferon-γ (INF-γ)], chemokines (i.e., macrophage inflammatory protein-2 (MIP-2)), and other inflammatory mediators (i.e., cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS)) in peripheral blood and hippocampus were measured by enzyme linked immunosorbent assay (ELISA).ResultsCompared with the Gn group, the Gi rats presented long escape latencies to find the platform. After acupuncture treatment, the escape latencies of the Ga group were rescued markedly when compared with the Gi group (P < 0.05). The proportion of CD4 + T lymphocytes in both spleen and peripheral blood in the Ga group increased (P < 0.05) in comparison with the Gi group. There is an obvious reduction in IL-1β (P < 0.05), IL-2 (P < 0.05), TNF-α (P < 0.01), INF-γ (P < 0.01), MIP-2 (P < 0.05), and iNOS (P < 0.01), coming along with the increased levels of IL-4 and IL-10 (P < 0.01) in the Ga group when compared with the Gi group. In addition, the hippocampus proinflammatory factors IL-1β (P < 0.01), IL-2 (P < 0.01), TNF-α (P < 0.05), INF-γ (P < 0.05), MIP-2 (P < 0.05), iNOS (P < 0.01), and COX-2 decreased in the Ga group, whereas the anti-inflammatory factors IL-4 and IL-10 (P < 0.01) increased.ConclusionThere are abnormal immune function and peripheral inflammation in VD rats. Acupuncture can regulate the peripheral immune function and inflammation of the VD rats and can improve the cognitive dysfunction of the rats.

Highlights

Vascular dementia (VD) is a serious cognitive dysfunction syndrome caused by cerebrovascular disease, which is the second most common type of dementia after Alzheimer’s disease (O’Brien and Thomas, 2015)
We used the bilateral common carotid artery occlusion (BCCAO) method to establish the VD rat model, which may be more stable and reliable to study the physiopathological mechanisms of cognitive impairment related to chronic cerebral ischemia (Zhang et al, 2014)
On the one hand, we found that the proportion of T cells and CD4+ helper T cells in the peripheral blood and spleen of the Gi group decreased in varying degrees, accompanied by the decrease in the ratio of CD4/CD8, which means that there is an abnormal immune function in the VD rats

Summary

Introduction

Vascular dementia (VD) is a serious cognitive dysfunction syndrome caused by cerebrovascular disease, which is the second most common type of dementia after Alzheimer’s disease (O’Brien and Thomas, 2015). Dementia caused by ischemic brain damage is the most common type (Venkat et al, 2015). We used the bilateral common carotid artery occlusion (BCCAO) method to establish the VD rat model, which may be more stable and reliable to study the physiopathological mechanisms of cognitive impairment related to chronic cerebral ischemia (Zhang et al, 2014). The long-term decrease in cerebral blood flow caused by the ligation of bilateral common carotid arteries (BCCAs), resulting in a series of pathological changes similar to VD, such as the sparsity of brain white matter (Cho et al, 2017; Nyitrai et al, 2018), hippocampus and cortex damage (Mori et al, 2017; Nyitrai et al, 2018), increased inflammation (Hei et al, 2018; Ranjithkumar et al, 2019), microglia activation (Yuan-Cheng et al, 2018; Impellizzeri et al, 2019), oxidative stress (Zhang et al, 2017), and blood–brain barrier damage (Edrissi et al, 2016). Some behavioral tests prove that the BCCAO model has poor performance in the eight-arm maze, Morris water maze (MWM), elevated T-maze, Y-maze, and object recognition test (Venkat et al, 2015), indicating that the model has a cognitive impairment such as learning and memory

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Conclusion