Role of Oleanolic acid in maintaining BBB integrity by targeting p38MAPK/VEGF/Src signaling pathway in rat model of subarachnoid hemorrhage

Abstract Background: Subarachnoid hemorrhage due to rupture of an intracranial aneurysm (IA) has quite a poor prognosis once after the onset despite of the modern technical advancement. The development of a novel therapeutic modality to prevent rupture or a diagnostic method to stratify dangerous lesions from many stable ones is thus mandatory for social health. To this end, mechanisms underlying rupture of lesions should be clarified. Methods: We and others have developed the rat model in which induced IAs spontaneously rupture resulting in subarachnoid hemorrhage. To clarify molecular cascades regulating rupture, we obtained gene expression profile data from rupture-prone lesions and revealed the enrichment of neutrophil-related terms in rupture-prone lesions by Gene Ontology analysis. Next, to validate a role of neutrophils in rupture of lesions, G-CSF was administered to a rat model. Results: As a result, G-CSF treatment not only increased number of neutrophils infiltrating in lesions but also significantly facilitated rupture of the lesions without increase the incidence. To clarify mechanisms how neutrophils facilitate rupture of IAs, we used HL-60 cell line and found that inflammatory stimuli enhanced the collagenolytic activity of MMP9. Immunohistochemical study using IA lesions from a rat model identified neutrophils as a major type of cells producing MMP9 around a site of rupture and consistently the collagenolytic activity of MMP9 was detected in ruptured lesions. Conclusions: These results combined together suggest the crucial role of neutrophil to rupture of IAs and also propose the potential of this type of cells as a candidate of therapeutic or diagnostic targets.

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Role of SCH79797 in Maintaining Vascular Integrity in Rat Model of Subarachnoid Hemorrhage

Stroke ◽

10.1161/strokeaha.113.678474 ◽

2013 ◽

Vol 44 (5) ◽

pp. 1410-1417 ◽

Cited By ~ 38

Author(s):

Junhao Yan ◽

Anatol Manaenko ◽

Sheng Chen ◽

Damon Klebe ◽

Qingyi Ma ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Rat Model ◽

Vascular Integrity

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Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury

Journal of Molecular Neuroscience ◽

10.1007/s12031-016-0792-x ◽

2016 ◽

Vol 60 (2) ◽

pp. 258-266 ◽

Cited By ~ 2

Author(s):

Yuan-Yuan Gao ◽

Xiao-Ya Hong ◽

Hong-Jun Wang

Keyword(s):

Rat Model ◽

Analgesic Effect ◽

Src Signaling ◽

Chronic Constrictive Injury

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Role of the AMPK signaling pathway in early brain injury after subarachnoid hemorrhage in rats

Acta Neurochirurgica ◽

10.1007/s00701-015-2370-3 ◽

2015 ◽

Vol 157 (5) ◽

pp. 781-792 ◽

Cited By ~ 15

Author(s):

Ji-Yang An ◽

Li-Li Zhou ◽

Peng Sun ◽

Hong-Gang Pang ◽

Dan-Dong Li ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Signaling Pathway ◽

Early Brain Injury ◽

Ampk Signaling

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Protective Role of Apocynin via Suppression of Neuronal Autophagy and TLR4/NF-κB Signaling Pathway in a Rat Model of Traumatic Brain Injury

Neurochemical Research ◽

10.1007/s11064-017-2372-z ◽

2017 ◽

Vol 42 (11) ◽

pp. 3296-3309 ◽

Cited By ~ 18

Author(s):

Yan Feng ◽

Changmeng Cui ◽

Xin Liu ◽

Qiang Wu ◽

Fuguang Hu ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Signaling Pathway ◽

Rat Model ◽

Protective Role ◽

Neuronal Autophagy

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Neuroprotective role of an N-acetyl serotonin derivative via activation of tropomyosin-related kinase receptor B after subarachnoid hemorrhage in a rat model

Neurobiology of Disease ◽

10.1016/j.nbd.2015.01.009 ◽

2015 ◽

Vol 78 ◽

pp. 126-133 ◽

Cited By ~ 19

Author(s):

Junjia Tang ◽

Qin Hu ◽

Yujie Chen ◽

Fei Liu ◽

Yun Zheng ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Rat Model

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EGCG Promotes Neurite Outgrowth through the Integrin β1/FAK/p38 Signaling Pathway after Subarachnoid Hemorrhage

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8810414 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Yuyuan Zhang ◽

Mengguo Han ◽

Xiaoxue Sun ◽

Guojun Gao ◽

Guoying Yu ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Neurite Outgrowth ◽

Signaling Pathway ◽

Cell Injury ◽

Integrin Β1 ◽

Neuroprotective Effects ◽

Neurological Score ◽

Biological Component ◽

Abnormal Neurites

The abnormal neurites have long been regarded as the main player contributing to the poor outcome of patients with subarachnoid hemorrhage (SAH). (-)-Eigallocatechin-3-gallate (EGCG), the major biological component of tea catechin, exhibited strong neuroprotective effects against central nervous system diseases; however, the role of EGCG-mediated neurite outgrowth after SAH has not been delineated. Here, the effect of reactive oxygen species (ROS)/integrin β1/FAK/p38 pathway on neurite outgrowth was investigated. As expected, oxyhemoglobin- (OxyHb-) induced excessive ROS level was significantly reduced by EGCG as well as antioxidant N-acetyl-l-cysteine (NAC). Consequently, the expression of integrin β1 was significantly inhibited by EGCG and NAC. Meanwhile, EGCG significantly inhibited the overexpression of phosphorylated FAK and p38 to basal level after SAH. As a result, the abnormal neurites and cell injury were rescued by EGCG, which eventually increased energy generation and neurological score after SAH. These results suggested that EGCG promoted neurite outgrowth after SAH by inhibition of ROS/integrin β1/FAK/p38 signaling pathway. Therefore, EGCG might be a new pharmacological agent that targets neurite outgrowth in SAH therapy.

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