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

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.

scholarly journals The Neuroprotective Effects of Necrostatin-1 on Subarachnoid Hemorrhage in Rats Are Possibly Mediated by Preventing Blood–Brain Barrier Disruption and RIP3-Mediated Necroptosis

2019 ◽  
Vol 28 (11) ◽  
pp. 1358-1372 ◽  
Author(s):  
Jingsen Chen ◽  
Hanghuang Jin ◽  
Hangzhe Xu ◽  
Yucong Peng ◽  
Liyong Jie ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Blood Brain Barrier ◽  
New Drugs ◽  
Brain Barrier ◽  
Lesion Volume ◽  
Brain Swelling ◽  
Neuroprotective Effects ◽  
Pharmaceutical Therapy ◽  
Blood Brain

Despite the substantial efforts to elucidate the role of early brain injury in subarachnoid hemorrhage (SAH), an effective pharmaceutical therapy for patients with SAH continues to be unavailable. This study aims to reveal the role of necroptosis after SAH, and explore whether the disruption of the blood–brain barrier (BBB) and RIP3-mediated necroptosis following SAH in a rat SAH model are altered by necrostatin-1 via its selective inhibition of receptor-interacting protein kinase 1 (RIP1). Sixty-five rats were used in the experiments. The SAH model was established using endovascular perforation. Necrostatin-1 was intracerebroventricularly injected 1 h before SAH induction. The neuroprotective effects of necrostatin-1 were evaluated with multiple methods such as magnetic resonance imaging (MRI) scanning, immunohistochemistry, propidium iodide (PI) labeling, and western blotting. Pretreatment with necrostatin-1 attenuated brain swelling and reduced the lesion volume on T2 sequence and ventricular volume on MRI 72 h after SAH induction. Albumin leakage and the degradation of tight junction proteins were also ameliorated by necrostatin-1 administration. In addition, necrostatin-1 decreased the number of PI-positive cells in the basal cortex, reduced the levels of the RIP3 and MLKL proteins, and inhibited the production of the pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Based on the findings from the present study, the selective RIP1 inhibitor necrostatin-1 functioned as a neuroprotective agent after SAH by attenuating brain swelling and BBB disruption. Moreover, the necrostatin-1 pretreatment prevented SAH-induced necroptosis by suppressing the activity of the RIP3/MLKL signaling pathway. These results will provide insights into new drugs and pharmacological targets to manage SAH, which are worth further study.

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

2015 ◽  
Vol 157 (5) ◽  
pp. 781-792 ◽  
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

scholarly journals Cytoprotective effects of adrenomedullin in glomerular cell injury: Central role of cAMP signaling pathway

1997 ◽  
Vol 52 (4) ◽  
pp. 917-925 ◽  
Author(s):  
Eduardo N. Chini ◽  
Claudia C.S. Chini ◽  
Chad Bolliger ◽  
Michihisa Jougasaki ◽  
Joseph P. Grande ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Cell Injury ◽  
Camp Signaling ◽  
Glomerular Cell ◽  
Camp Signaling Pathway

scholarly journals MFG-E8 attenuates neuro-inflammation in subarachnoid hemorrhage through driving microglial M2 polarization via modulating Integrin β3/SOCS3/STAT3 signaling pathway

2020 ◽  
Author(s):  
Yongyue Gao ◽  
Zong Zhuang ◽  
Yue Lu ◽  
Lingyun Wu ◽  
Guangjie Liu ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Signaling Pathway ◽  
Microglial Polarization ◽  
Integrin Β3 ◽  
Stat3 Signaling ◽  
Stat3 Signaling Pathway ◽  
Neuro Inflammation ◽  
Anti Inflammation ◽  
M2 Phenotype

Abstract Background Increasing evidence suggests microglial polarization plays an important role in the pathological processes of neuro-inflammation following subarachnoid hemorrhage (SAH). Previous studies indicated that milk fat globule-EGF factor-8 (MFG-E8) has the potential in anti-apoptosis and anti-inflammation in cerebral ischemia. However, the effects of MFG-E8 on microglial polarization have not been evaluated after SAH. Therefore, the aim of this study was to explore the role of MFG-E8 on anti-inflammation, and its potential mechanism on microglial polarization following SAH. Methods We established the SAH model via prechiasmatic cistern Blood injection in mice. Double-immunofluorescence staining, Western blotting and quantitative real-time polymerase chain reaction (q-PCR) were performed to investigate the expression and cellular distribution of MFG-E8. Two different dosages (1 μg and 5 μg) of recombinant human MFG-E8 (rhMFG-E8) were injected intracerebroventricular (i.c.v.) at 1 h after SAH. Brain water content, neurological scores, beam-walking score, Fluoro-Jade C (FJC) and terminal deoxynucleotidyl transferase dUTP nick endlabeling staining (TUNEL) were measured at 24 h. Intervention of MFG-E8, integrin β3 and phosphorylation of STAT3 were achieved by specific siRNAs (500 pmol/5 µl) and STAT3 inhibitor Stattic (5 µM). The potential signal pathway and microglial polarization were measured by immunofluorescence labeling and Western blotting. Results SAH induction increased the levels of inflammation mediators, the proportion of M1 and caused neuronal apoptosis in mice at 24 h. Treatment with rhMFG-E8 (5 µg) remarkably decreased brain edema, improved neurological functions, reduced the levels of pro-inflammation factors, and promoted microglia shifted to M2 phenotype. However, knockdown MFG-E8 and integrin β3 via siRNA abolished the effects of MFG-E8 on anti-inflammation and M2 phenotype polarization. STAT3 inhibitor Stattic further clarified the role of rhMFG-E8 on microglial polarization through regulating the protein levels of integrin β3/SOCS3/STAT3 pathway. Conclusions rhMFG-E8 inhibits neuron-inflammation through transformation microglial phenotype towards M2 after SAH, which may be mediated by modulation of the integrin β3/SOCS3/STAT3 signaling pathway, and highlighting rhMFG-E8 as a potentially therapeutic target for the treatment of SAH patients.

Role of LncRNA MALAT-1 in hypoxia-induced PC12 cell injury via regulating p38MAPK signaling pathway

2018 ◽  
Vol 670 ◽  
pp. 41-47 ◽  
Author(s):  
Lin Yang ◽  
Fei Xu ◽  
Miao Zhang ◽  
Xiao-Ying Shang ◽  
Xin Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Pc12 Cell ◽  
Cell Injury ◽  
P38mapk Signaling

Role of Akt signaling pathway in delayed cerebral vasospasm after subarachnoid hemorrhage in rats

2013 ◽  
Vol 155 (11) ◽  
pp. 2063-2070 ◽  
Author(s):  
Jin-Ning Song ◽  
Ji-Yang An ◽  
Guang-Shan Hao ◽  
Dan-Dong Li ◽  
Peng Sun ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Signaling Pathway ◽  
Cerebral Vasospasm ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Delayed Cerebral Vasospasm

Neuroprotective Effects of Magnesium Lithospermate B against Subarachnoid Hemorrhage in Rats

2018 ◽  
Vol 46 (06) ◽  
pp. 1225-1241 ◽  
Author(s):  
Yucong Peng ◽  
Pingyou He ◽  
Linfeng Fan ◽  
Hangzhe Xu ◽  
Jianru Li ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Salvia Miltiorrhiza ◽  
Neurological Deficits ◽  
Sprague Dawley ◽  
Chinese Medicinal Herb ◽  
Neuroprotective Effects ◽  
Sprague Dawley Rats ◽  
Apoptotic Protein ◽  
Magnesium Lithospermate B

Subarachnoid hemorrhage (SAH) is a severe cerebrovascular disease with few effective pharmacotherapies available. Salvia miltiorrhiza, a traditional Chinese medicinal herb, has been widely used to treat cardiovascular diseases for centuries. Recent studies have demonstrated that magnesium lithospermate B (MLB), a bioactive ingredient extracted from Salvia miltiorrhiza, exerts neuroprotective effects in several central nervous system insults. However, little is known about the role of MLB in SAH-induced brain injury and the exact molecular mechanism. In the current study, we studied the neuroprotective effects of MLB in SAH and explored the potential mechanism. Adult male Sprague–Dawley rats were subjected to an endovascular perforation process to produce an SAH model. MLB was administrated intraperitoneally at 30[Formula: see text]min after SAH with a dose of 25[Formula: see text]mg/kg or 50[Formula: see text]mg/kg. We found that administration of MLB significantly attenuated brain edema and neurological deficits after SAH. In addition, immunofluorescence staining demonstrated that MLB dose-dependently inhibited the activation of microglia and reduced neuronal apoptosis. Western blot analysis showed that MLB decreased the expression of inflammatory cytokine TNF-[Formula: see text] and pro-apoptotic protein cleaved caspase-3. More importantly, MLB increased the expression of SIRT1, while inhibited the acetylation of NF-[Formula: see text]B. Furthermore, pretreatment with sirtinol (a selective inhibitor of SIRT1) reversed all the aforementioned effects of MLB after SAH. In conclusion, our results indicated that MLB exerted robust neuroprotective effects against SAH via suppressing neuroinflammation and apoptosis. These neuroprotective effects of MLB against SAH might be exerted via regulating the SIRT1/NF-[Formula: see text]B pathway. MLB or the SIRT1/NF-[Formula: see text]B pathway could be a novel and promising therapeutic strategy for SAH management.

scholarly journals Naringenin reduces early brain injury in subarachnoid hemorrhage (SAH) mice: The role of the AMPK/SIRT3 signaling pathway

2020 ◽  
Vol 72 ◽  
pp. 104043
Author(s):  
Hanhai Zeng ◽  
Bo Shao ◽  
Jianfeng Zhuang ◽  
Yucong Peng ◽  
Huaijun Chen ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Signaling Pathway ◽  
Early Brain Injury

scholarly journals Sema4D Aggravated LPS-Induced Injury via Activation of the MAPK Signaling Pathway in ATDC5 Chondrocytes

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jinlai Lei ◽  
Yahui Fu ◽  
Yan Zhuang ◽  
Kun Zhang
Keyword(s):  
Signaling Pathway ◽  
Cell Injury ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Degenerative Joint Disease ◽  
Mapk Signaling Pathway ◽  
Joint Disease ◽  
Promoting Effect ◽  
Bone Injury

Osteoarthritis (OA) is the most common chronic degenerative joint disease, and it remains the main cause of chronic disability in elderly individuals. Sema4D (semaphorin 4D) is involved in the immune system and related to bone injury, osteoporosis, osteoblast differentiation, and rheumatoid arthritis. However, the role of Sema4D in OA remains unclear. Hence, the LPS-stimulated chondrocyte cell injury model was constructed in this study to investigate the role of Sema4D in OA development. The results showed that Sema4D was increased in LPS-treated ATDC5 cells, and the knockdown of Sema4D suppressed the decline of cell viability, the increase of cell apoptosis, and the increase of IL-6, IL-1β, and TNF-α secretion in ATDC5 cells induced by LPS. Meanwhile, Sema4D overexpression aggravated the cell injury triggered by LPS, and inhibiting Plexin B1 partly abolished the effect of Sema4D overexpression on LPS-induced chondrocyte injury. Furthermore, silencing of Sema4D blocked the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. Enhanced Sema4D promoted the activation of the MAPK pathway in LPS-stimulated ATDC5 cells. What is more, inhibiting the MAPK signaling pathway abolished the promoting effect of Sema4D overexpression on LPS-induced chondrocyte injury. Therefore, our study suggested that the knockdown of Sema4D protects ATDC5 cells against LPS-induced injury through inactivation of the MAPK signaling pathway via interacting with Plexin B1.

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