Tetramethylpyrazine attenuates blood-brain barrier disruption in ischemia/reperfusion injury through the JAK/STAT signaling pathway

Gong, Pian; Zhang, Zhan; Zou, Yichun; Tian, Qi; Han, Shoumeng; Zhou, Xu; Liao, Jianming; Gao, Ling; Chen, Qianxue; Li, Mingchang

doi:10.1016/j.ejphar.2019.04.028

Cited by 56 publications

(46 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In order to understand how the IL-6/JAK2/STAT3/ MMP-9 pathway regulates the microvessels under hypoxia, the specific processes should be analyzed in detail. IL-6, one of the dominant inflammatory cytokines [24][25][26][27], markedly upregulates the phosphorylation of JAK2 by binding to IL-6 receptor α (IL-6Rα) and activating gp130 [12]. P-JAK2 subsequently induces STAT3 phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

“…e Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway plays a vital role in mediating angiogenesis against ischemic injury [11][12][13][14][15][16][17]. Importantly, JAK2/STAT3 signaling has been specifically shown to protect against cerebral ischemia-reperfusion injury by inducing microvessel proliferation [18][19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway

Zhu

Yang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

Chronic hypoxia (CH) is characterized by long-term hypoxia that is associated with microvessel proliferation and basal membrane (BM) degradation in tissues. The IL-6/JAK2/STAT3/MMP-9 pathway has been described in a variety of human cancers and plays an essential role in microvessel proliferation and BM degradation. Therefore, this study investigated the role of the IL-6/JAK2/STAT3/MMP-9 pathway in hypoxia-mediated microvessel proliferation and BM degradation in the rat bone marrow. Eighty pathogen-free Sprague Dawley male rats were randomly divided into four groups (20 per group)—control group, CH group (exposed to hypoxia in a hypobaric chamber at a simulated altitude of 5000 m for 28 d), CH + STAT3 inhibitor group (7.5 mg/kg/d), and CH + DMSO group. Microvessel density (MVD) and BM degradation in the bone marrow were determined by immunofluorescence staining and transmission electron microscopy. Serum IL-6 levels were assessed by enzyme-linked immunosorbent assay (ELISA), and the levels of P-JAK2, P-STAT3, and MMP-9 were assessed by western blot analysis and real-time reverse transcription PCR (RT-PCR). Hypoxia increased serum IL-6 levels, which in turn increased JAK2 and STAT3 phosphorylation, which subsequently upregulated MMP-9. Overexpression of MMP-9 significantly promoted the elevation of MVD and BM degradation. Inhibition of STAT3 using an inhibitor, SH-4-54, significantly downregulated MMP-9 expression and decreased MVD and BM degradation. Surprisingly, STAT3 inhibition also decreased serum IL-6 levels and JAK2 phosphorylation. Our results suggest that the IL-6/JAK2/STAT3/MMP-9 pathway might be related to CH-induced microvessel proliferation and BM degradation in the bone marrow.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway

Zhu

Yang

et al. 2020

BioMed Research International

View full text Add to dashboard Cite

show abstract

“…In an animal model of ischemia/reperfusion injury, Gong et al found that inhibition of JAK/STAT signaling activation increased TJ levels and reduced BBB permeability. 151 Chaudhuri et al also demonstrated that activated STAT1 induces IL-6 expression and reduces the expression of claudin-5, ZO-1 and ZO-2 in BMEC. The STAT1 inhibitor fludarabine attenuates this downregulation of claudin-5 and ZO-1 and blocks the migration of monocytes across the BBB.…”

Section: C-jun N-terminal Kinase (Jnk) Signaling Pathwaymentioning

confidence: 96%

<p>The Impact of Gut Microbiota Disorders on the Blood–Brain Barrier</p>

Wei¹,

Zhu²,

Feng³

et al. 2020

IDR

View full text Add to dashboard Cite

The gut microbiota is symbiotic with the human host and has been extensively studied in recent years resulting in increasing awareness of the effects of the gut microbiota on human health. In this review, we summarize the current evidence for the effects of gut microbes on the integrity of the cerebral blood-brain barrier (BBB), focusing on the pathogenic impact of gut microbiota disorders. Based on our description and summarization of the effects of the gut microbiota and its metabolites on the nervous, endocrine, and immune systems and related signaling pathways and the resulting destruction of the BBB, we suggest that regulating and supplementing the intestinal microbiota as well as targeting immune cells and inflammatory mediators are required to protect the BBB.

show abstract

“…The presence of hyper-phosphorylated tau accumulating in neurofibrillary tangles is a characteristic of CTE (Omalu et al, 2010). Even if phospho-tau is detectable only at low levels acutely after TBI (Smith et al, 2003;Blennow et al, 2012;Goldstein et al, 2012;Mannix et al, 2013), a specific form of phospho-tau can be produced in response to TBI (cis P-tau) (Kondo et al, 2015). This protein spreads throughout the brain, harming cells and leading to post-traumatic neurodegeneration and dementia.…”

Section: Autoantibodies and Post-traumatic Encephalopathymentioning

confidence: 99%

Peripheral Routes to Neurodegeneration: Passing Through the Blood–Brain Barrier

Giannoni

Claeysen

Noè

et al. 2020

Front. Aging Neurosci.

View full text Add to dashboard Cite

A bidirectional crosstalk between peripheral players of immunity and the central nervous system (CNS) exists. Hence, blood-brain barrier (BBB) breakdown is emerging as a participant mechanism of dysregulated peripheral-CNS interplay, promoting diseases. Here, we examine the implication of BBB damage in neurodegeneration, linking it to peripheral brain-directed autoantibodies and gut-brain axis mechanisms. As BBB breakdown is a factor contributing to, or even anticipating, neuronal dysfunction(s), we here identify contemporary pharmacological strategies that could be exploited to repair the BBB in disease conditions. Developing neurovascular, add on, therapeutic strategies may lead to a more efficacious pre-clinical to clinical transition with the goal of curbing the progression of neurodegeneration.

show abstract

Tetramethylpyrazine attenuates blood-brain barrier disruption in ischemia/reperfusion injury through the JAK/STAT signaling pathway

Cited by 56 publications

References 35 publications

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway

Chronic Hypoxia-Induced Microvessel Proliferation and Basal Membrane Degradation in the Bone Marrow of Rats Regulated through the IL-6/JAK2/STAT3/MMP-9 Pathway

<p>The Impact of Gut Microbiota Disorders on the Blood–Brain Barrier</p>

Peripheral Routes to Neurodegeneration: Passing Through the Blood–Brain Barrier

Contact Info

Product

Resources

About