HMGB1 Neutralization Attenuates Hippocampal Neuronal Death and Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion via Suppressing Inflammatory Responses and Oxidative Stress

Hei, Yue; Chen, Rong; Yi, Xiuli; Long, Qianfa; Gao, Dakuan; Liu, Weiping

doi:10.1016/j.neuroscience.2018.05.010

Cited by 47 publications

(31 citation statements)

References 37 publications

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“…It is well established that inflammatory responses, including activation of glial cells and production of inflammatory cytokines such as IL-1β, IL-6, COX-2, iNOS, and TNF-α, induced by CCH could further result in neuronal cell death and cognitive deficits [32,33]. Diabetes was also shown to increase microglial activation and the production of proinflammatory cytokines in previous studies [34,35].…”

Section: Discussionmentioning

confidence: 90%

TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

Zhang

Liu

Zheng

et al. 2020

J Neuroinflammation

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Background: Diabetes mellitus (DM) and chronic cerebral hypoperfusion(CCH)are both risk factors for cognitive impairment. However, whether DM and CCH can synergistically promote cognitive impairment and the related pathological mechanisms remain unknown. Methods:To investigate the effect of DM and CCH on cognitive function, rats fed with high-fat diet (HFD) and injected with low-dose streptozotocin (STZ) followed by bilateral common carotid artery occlusion (BCCAO) were induced to mimic DM and CCH in vivo and mouse BV2 microglial cells were exposed to hypoxia and/or high glucose to mimic CCH complicated with DM pathologies in vitro. To further explore the underlying mechanism, TREM-2-specific small interfering RNA and TREM-2 overexpression lentivirus were used to knock out and overexpress TREM-2, respectively.Results: Cognitive deficits, neuronal cell death, neuroinflammation with microglial activation, and TREM-2-MAPK signaling were enhanced when DM was superimposed on CCH both in vivo and in vitro. Manipulating TREM-2 expression levels markedly regulated the p38 MAPK signaling and the inflammatory response in vitro. TREM-2 knockout intensified while TREM-2 overexpression suppressed the p38 MAPK signaling and subsequent proinflammatory mediator production under high glucose and hypoxia condition.Conclusions: These results suggest that TREM-2 negatively regulates p38 MAPK-mediated inflammatory response when DM was synergistically superimposed on CCH and highlight the importance of TREM-2 as a potential target of immune regulation in DM and CCH.

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Section: Discussionmentioning

confidence: 90%

TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

Zhang

Liu

Zheng

et al. 2020

J Neuroinflammation

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“…It is a known danger signal or damage associated molecular pattern (Hei et al . ), and was first reported in 1973 as a non‐histone chromosomal protein (Ranzato et al . ).…”

Section: Insights Into Hmgb1 Biologymentioning

confidence: 99%

“…HMGB1 is an intriguing protein with complex biochemistry. It is a known danger signal or damage associated molecular pattern (Hei et al 2018), and was first reported in 1973 as a non-histone chromosomal protein (Ranzato et al 2010). Intracellular and extracellular HMGB1 protein has demonstrated several crucial roles in inflammation, including being implicated in sterile inflammation, immunity and neurodegenerative conditions, making it an attractive, and emerging target for therapeutic intervention (Andersson and Tracey 2011).…”

Section: Insights Into Hmgb1 Biologymentioning

confidence: 99%

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

Paudel

Semple

Jones

et al. 2019

Journal of Neurochemistry

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Epilepsy is a serious neurological condition exhibiting complex pathology and deserving of more serious attention. More than 30% of people with epilepsy are not responsive to more than 20 anti‐epileptic drugs currently available, reflecting an unmet clinical need for novel therapeutic strategies. Not much is known about the pathogenesis of epilepsy, but evidence indicates that neuroinflammation might contribute to the onset and progression of epilepsy following acquired brain insults. However, the molecular mechanisms underlying these pathophysiological processes are yet to be fully understood. The emerging research suggests that high‐mobility group box protein 1 (HMGB1), a DNA‐binding protein that is both actively secreted by inflammatory cells and released by necrotic cells, might contribute to the pathogenesis of epilepsy. HMGB1 as an initiator and amplifier of neuroinflammation, and its activation is implicated in the propagation of seizures in animal models. The current review will highlight the potential role of HMGB1 in the pathogenesis of epilepsy, and implications of HMGB1‐targeted therapies against epilepsy. HMGB1 in this context is an emerging concept deserving further exploration. Increased understanding of HMGB1 in seizures and epilepsy will pave the way in designing novel and innovative therapeutic strategies that could modify the disease course or prevent its development.

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“…Longterm CCH can trigger neurodegeneration and eventually lead to progressive cognitive dysfunction [3][4][5]. Clinical research has shown that CCH is the common pathological foundation of Alzheimer's disease, vascular dementia, vascular cognitive impairment, and other neurodegenerative diseases [6][7][8]. Therefore, understanding the mechanisms underlying CCH will facilitate the development of therapeutic strategies for the prevention and treatment of CCH-induced neurodegeneration [6].…”

Section: Introductionmentioning

confidence: 99%

Electroacupuncture Improved Chronic Cerebral Hypoperfusion-Induced Anxiety-Like Behavior and Memory Impairments in Spontaneously Hypertensive Rats by Downregulating the ACE/Ang II/AT1R Axis and Upregulating the ACE2/Ang-(1-7)/MasR Axis

Feng

Líu

et al. 2020

Neural Plasticity

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Electroacupuncture (EA) can effectively alleviate anxiety disorders and memory impairments caused by various neurodegenerative diseases; however, the molecular mechanisms underlying its neuroprotective effects are unclear. Previous studies have shown that the renin-angiotensin system (RAS) comprises of two axes with mutual antagonism: the classical angiotensin converting enzyme/angiotensin II/angiotensin II type 1 receptor (ACE/Ang II/AT1R) axis and the protective angiotensin converting enzyme 2/angiotensin-(1-7)/Mas receptor (ACE2/Ang-(1-7)/MasR) axis. In this study, we observed that chronic cerebral hypoperfusion (CCH) mediated anxiety-like behavior and memory impairments in spontaneously hypertensive rats (SHR) via upregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and the partial hippocampal protective axis (ACE2/Ang-(1-7)). However, Ang II levels were much higher than those of Ang-(1–7), indicating that the ACE/Ang II/AT1R axis plays a dominant role in the comorbidity of CCH and hypertension. Moreover, candesartan cilexetil (Canc) and perindopril (Peril) were used as positive control drugs. We found that EA, Canc, and Peril attenuated CCH-induced anxiety-like behavior and memory impairments in SHR, potentially via downregulation of the hippocampal classical axis (ACE/Ang II/AT1R) and upregulation of the whole hippocampal protective axis (ACE2/Ang-(1-7)/MasR). These results suggest that EA therapy for CCH with hypertension may be mediated by two hippocampal RAS axes.

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HMGB1 Neutralization Attenuates Hippocampal Neuronal Death and Cognitive Impairment in Rats with Chronic Cerebral Hypoperfusion via Suppressing Inflammatory Responses and Oxidative Stress

Cited by 47 publications

References 37 publications

TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

TREM-2-p38 MAPK signaling regulates neuroinflammation during chronic cerebral hypoperfusion combined with diabetes mellitus

High mobility group box 1 (HMGB1) as a novel frontier in epileptogenesis: from pathogenesis to therapeutic approaches

Electroacupuncture Improved Chronic Cerebral Hypoperfusion-Induced Anxiety-Like Behavior and Memory Impairments in Spontaneously Hypertensive Rats by Downregulating the ACE/Ang II/AT1R Axis and Upregulating the ACE2/Ang-(1-7)/MasR Axis

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