Non-invasive Vagus Nerve Stimulation Protects Against Cerebral Ischemia/Reperfusion Injury and Promotes Microglial M2 Polarization Via Interleukin-17A Inhibition

Zhao, Xiaoping; Zhao, Yuan; Qin, Xiaoya; Wan, Li-Yuan; Fan, Xiaoxuan

doi:10.1007/s12031-018-1227-7

Cited by 53 publications

(45 citation statements)

References 32 publications

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“…We found that the expression of IL-17 in the ischemic cortex and hippocampus of stroke mice treated with As IV was decreased remarkably by both immunohistochemistry and Western blot analysis (Figures 3A, B) and the expression of IL-17 increased gradually and slowly after stroke as time went on and lagged far behind the appearance of apoptosis ( Figure 3C). Consistently, previous results also suggest that the over expression of IL-17 indicates a poorer treatment effect and prognosis for ischemic stroke (He et al, 2019;Tian et al, 2019;Zhou et al, 2019), which always abolishes some neuroprotective effect (Ma et al, 2018;Sun et al, 2018;Zhao et al, 2019) and it can be reduced by As IV (Jin et al, 2017;Zhang et al, 2018). So, IL-17 expression is upregulated remarkably by ischemic stroke, which can be reversed by As IV, indicating IL-17 is a key regulation factor for As IV's neuroprotective effect on ischemic stroke.…”

Section: A B C Dsupporting

confidence: 79%

“…Some innate lymphocytes, like brain-infiltrating interleukin-17 (IL-17)-positive gd T cells, are established as major initial IL-17 producers in acute stroke (Arunachalam et al, 2017). IL-17 is an important inflammatory factor and its over-expression indicates a poorer treatment effect and prognosis for ischemic stroke (He et al, 2019;Tian et al, 2019;Zhou et al, 2019), which always abolishes some neuroprotective effect (Sun et al, 2018;Ma et al, 2018;Zhao et al, 2019). IL-17 has a quite complex role in regulating adult neurogenesis.…”

Section: Introductionmentioning

confidence: 99%

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Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

et al. 2020

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Background: Stroke remains a leading cause of adult disability and the demand for stroke rehabilitation services is growing, and Astragaloside IV (As IV), a primary bioactive compound of Radix Astragali: Astragalus mongholicus Bunge (Fabaceae), may be a promising stroke therapy. Methods: To access the effect of As IV on adult mice after ischemic stroke, a photochemical ischemia model was established on C57BL/6 mice, which were intravenously administered As IV for three consecutive days later. And then the cognitive benefits and hippocampal neurogenesis were evaluated by Morris Water Maze (MWM) test, Golgi staining, and immunohistochemical staining in vivo and in vitro. Furthermore, to find out the underlying mechanism, interleukin-17 (IL-17) knockout (KO) mice were used, through RNA sequence (RNA-seq) analysis and immunohistochemistry. Then the mechanism of neurogenesis promoted by As IV was observed by western blot both in vivo and in vitro. Specifically, As IV, recombinant mouse IL-17A and IL-17F, and Wingless/integrated (Wnt)-expressing virus was administered respectively in neural stem cells (NSCs), and then their diameters and protein expression of Nestin, IL-17, and Wnt pathway relevant protein, were measured in vitro. Results: Administering As IV resulted in significant amelioration of stroke-induced cognitive deficits. And more hippocampal neurons with normal morphology, significant increments in the length of the apical dendrites, and the density of their spines were observed in As IV-treated mice. Furthermore, the immunohistochemistry staining of DCX/ BrdU and Sox2/Nestin showed As IV could promote hippocampal neurogenesis and NSC proliferation after ischemic stroke, as well as in vitro. For the mechanism underlying, IL-17 expression was downregulated significantly by As IV treatment and knocking out IL-17 was associated with nervous regeneration and synapse repair according to the analysis of RNA-seq. Consistent to As IV treatment, knocking out IL-17 showed some promotion on hippocampal neurogenesis and proliferation of NSCs, with activating Wnt pathway after

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Section: A B C Dsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

et al. 2020

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“…The efficacy of a regimen of VNS for 60 min (six series of 2-min duration substimulations at a 10-min interval, consisting of 1 msec duration pulses of 5 kHz sinewaves, repeated at 25 Hz with an average voltage of 15 V) was studied. This VNS (vs. sham stimulation applied on left femur) results in considerable neuroprotection related to increased microglial M2 polarization mediated by IL-17A expression (Zhao et al 2019).…”

Section: Vagus Nerve Stimulation In Animal Models Of Inflammatory Conmentioning

confidence: 92%

“…Auricular VNS triggers neuronal activation in the NTS and DMN, and vagotomy abrogates its anti-inflammatory effects; these observations clearly point to the mediating role of efferent vagus nerve signaling in the context of murine ileus and endotoxemia (Hong et al 2018b). Recent studies have also shown the efficacy of other approaches of noninvasive VNS in alleviating CNS inflammation (neuroinflammation) and other brain derangements in mice by affective microglial activation toward neuroprotective phenotype (Kaczmarczyk et al 2017;Zhao et al 2019). For instance, noninvasive transcutaneous stimulation of the right cervical vagus nerve was recently used in a mouse model of focal cerebral ischemia (Zhao et al 2019).…”

Section: Vagus Nerve Stimulation In Animal Models Of Inflammatory Conmentioning

confidence: 95%

“…Recent studies have also shown the efficacy of other approaches of noninvasive VNS in alleviating CNS inflammation (neuroinflammation) and other brain derangements in mice by affective microglial activation toward neuroprotective phenotype (Kaczmarczyk et al 2017;Zhao et al 2019). For instance, noninvasive transcutaneous stimulation of the right cervical vagus nerve was recently used in a mouse model of focal cerebral ischemia (Zhao et al 2019). The efficacy of a regimen of VNS for 60 min (six series of 2-min duration substimulations at a 10-min interval, consisting of 1 msec duration pulses of 5 kHz sinewaves, repeated at 25 Hz with an average voltage of 15 V) was studied.…”

Section: Vagus Nerve Stimulation In Animal Models Of Inflammatory Conmentioning

confidence: 99%

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Bioelectronic Medicine: From Preclinical Studies on the Inflammatory Reflex to New Approaches in Disease Diagnosis and Treatment

Pavlov

Chavan

Tracey

2019

Cold Spring Harb Perspect Med

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Bioelectronic medicine is an evolving field in which new insights into the regulatory role of the nervous system and new developments in bioelectronic technology result in novel approaches in disease diagnosis and treatment. Studies on the immunoregulatory function of the vagus nerve and the inflammatory reflex have a specific place in bioelectronic medicine. These studies recently led to clinical trials with bioelectronic vagus nerve stimulation in inflammatory diseases and other conditions. Here, we outline key findings from this preclinical and clinical research. We also point to other aspects and pillars of interdisciplinary research and technological developments in bioelectronic medicine.

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Interactions between the Autonomic Nervous System and the Immune System after Stroke

Zhu

Huang

et al. 2022

Comprehensive Physiology

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Acute stroke is one of the leading causes of morbidity and mortality worldwide. Stroke-induced immune-inflammatory response occurs in the perilesion areas and the periphery. Although strokeinduced immunosuppression may alleviate brain injury, it hinders brain repair as the immuneinflammatory response plays a bidirectional role after acute stroke. Furthermore, suppression of the systemic immune-inflammatory response increases the risk of life-threatening systemic bacterial infections after acute stroke. Therefore, it is essential to explore the mechanisms that underlie the stroke-induced immune-inflammatory response. Autonomic nervous system (ANS) activation is critical for regulating the local and systemic immune-inflammatory responses and may influence the prognosis of acute stroke. We review the changes in the sympathetic and parasympathetic nervous systems and their influence on the immune-inflammatory response after stroke. Importantly, this article summarizes the mechanisms on how ANS regulates the immune-inflammatory response through neurotransmitters and their receptors in immunocytes and immune organs after stroke.To facilitate translational research, we also discuss the promising therapeutic approaches modulating the activation of the ANS or the immune-inflammatory response to promote neurologic recovery after stroke.

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Non-invasive Vagus Nerve Stimulation Protects Against Cerebral Ischemia/Reperfusion Injury and Promotes Microglial M2 Polarization Via Interleukin-17A Inhibition

Cited by 53 publications

References 32 publications

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

Astragaloside IV Exerts Cognitive Benefits and Promotes Hippocampal Neurogenesis in Stroke Mice by Downregulating Interleukin-17 Expression via Wnt Pathway

Bioelectronic Medicine: From Preclinical Studies on the Inflammatory Reflex to New Approaches in Disease Diagnosis and Treatment

Interactions between the Autonomic Nervous System and the Immune System after Stroke

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