scholarly journals Angiotensin IV suppresses inflammation in the brains of rats with chronic cerebral hypoperfusion

2018 ◽  
Vol 19 (3) ◽  
pp. 147032031879958 ◽  
Author(s):  
Qing-Guang Wang ◽  
Xiao Xue ◽  
Yang Yang ◽  
Peng-Yu Gong ◽  
Teng Jiang ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Neurological Diseases ◽  
Amyloid Β ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Angiotensin Iv ◽  
Artificial Cerebrospinal Fluid ◽  
Ang Iv ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Introduction: This study aimed to evaluate the influence of central angiotensin IV (Ang IV) infusion on chronic cerebral hypoperfusion (CCH)-related neuropathological changes including amyloid-β (Aβ), hyperphosphorylated tau (p-tau) and the inflammatory response. Materials and methods: Rats with CCH received central infusion of Ang IV, its receptor AT4R antagonist divalinal-Ang IV or artificial cerebrospinal fluid for six weeks. During this procedure, the systolic blood pressure (SBP) was monitored, and the levels of Aβ42, p-tau and pro-inflammatory cytokines in the brain were detected. Results: Rats with CCH exhibited higher levels of Aβ42, p-tau and pro-inflammatory cytokines in the brain when compared with controls. Infusion of Ang IV significantly reduced the expression of pro-inflammatory cytokines in the brains of rats with CCH. Meanwhile, the reduction of pro-inflammatory cytokines levels caused by Ang IV was reversed by divalinal-Ang IV. During the treatment, the SBP in rats was not significantly altered. Conclusion: This study demonstrates for the first time that Ang IV dose-dependently suppresses inflammation through AT4R in the brains of rats with CCH, which is independent from SBP. These findings suggest that Ang IV/AT4R may represent a potential therapeutic target for CCH-related neurological diseases.

scholarly journals Chronic cerebral hypoperfusion alters amyloid-β peptide pools leading to cerebral amyloid angiopathy, microinfarcts and haemorrhages in Tg-SwDI mice

2017 ◽  
Vol 131 (16) ◽  
pp. 2109-2123 ◽  
Author(s):  
Natalia Salvadores ◽  
James L. Searcy ◽  
Philip R. Holland ◽  
Karen Horsburgh
Keyword(s):  
Amyloid Β ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Amyloid Angiopathy ◽  
Amyloid Β Peptide ◽  
Wild Type ◽  
Aβ Peptides ◽  
Bilateral Carotid ◽  
The Brain ◽  
Bilateral Carotid Artery

Cerebral hypoperfusion is an early feature of Alzheimer’s disease (AD) that influences the progression from mild cognitive impairment to dementia. Understanding the mechanism is of critical importance in the search for new effective therapies. We hypothesized that cerebral hypoperfusion promotes the accumulation of amyloid-β (Aβ) and degenerative changes in the brain and is a potential mechanism contributing to development of dementia. To address this, we studied the effects of chronic cerebral hypoperfusion induced by bilateral carotid artery stenosis on Aβ peptide pools in a transgenic mouse model of AD (transgenic mice with Swedish, Dutch and Iowa mutations in human amyloid precursor protein (APP) (Tg-SwDI)). Cerebrovascular integrity was characterized by quantifying the occurrence of microinfarcts and haemorrhages and compared with wild-type mice without Aβ. A significant increase in soluble Aβ peptides (Aβ40/42) was detected after 1 month of hypoperfusion in the parenchyma in parallel with elevated APP and APP proteolytic products. Following 3 months, a significant increase in insoluble Aβ40/42 was determined in the parenchyma and vasculature. Microinfarct load was significantly increased in the Tg-SwDI as compared with wild-type mice and further exacerbated by hypoperfusion at 1 and 3 months. In addition, the number of Tg-SwDI hypoperfused mice with haemorrhages was increased compared with hypoperfused wild-type mice. Soluble parenchymal Aβ was associated with elevated NADPH oxidase-2 (NOX2) which was exacerbated by 1-month hypoperfusion. We suggest that in response to hypoperfusion, increased Aβ production/deposition may contribute to degenerative processes by triggering oxidative stress promoting cerebrovascular disruption and the development of microinfarcts.

scholarly journals Chronic cerebral hypoperfusion accelerates amyloid β deposition in APPSwInd transgenic mice

2009 ◽  
Vol 1294 ◽  
pp. 202-210 ◽  
Author(s):  
Hiroshi Kitaguchi ◽  
Hidekazu Tomimoto ◽  
Masafumi Ihara ◽  
Masunari Shibata ◽  
Kengo Uemura ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Amyloid Β ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion

scholarly journals Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2773 ◽  
Author(s):  
Myeongjoo Son ◽  
Seyeon Oh ◽  
Junwon Choi ◽  
Ji Tae Jang ◽  
Chang Hu Choi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Cytokines ◽  
Brain Inflammation ◽  
Leptin Resistance ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
M1 Polarization ◽  
Activated Macrophage ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Obesity induces inflammation both in the adipose tissue and the brain. Activated macrophage infiltration, polarization of macrophages to a more inflammatory type (M1), and increased levels of pro-inflammatory cytokines are related to brain inflammation, which induces leptin resistance in the brain. Pyrogallol-phloroglucinol-6,6-bieckol (PPB), a compound from Ecklonia cava, has anti-inflammatory effects. In this study, we evaluated the effects of PPB effect M1 polarization and inflammation and its ability to restore the effects of leptin, such as a decrease in appetite and body weight. We administered PPB to diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice, evaluated macrophage activation, polarization, and changes of inflammatory cytokine level in adipose tissue and brain, and determined the effect of PPB on leptin resistance or leptin sensitivity in the brain. The levels of activated macrophage marker, M1/M2, and pro-inflammatory cytokines were increased in the adipose tissue and brain of DIO and ob/ob mice than control. TLR4 expression, endoplasmic reticulum (ER) stress, and NF-κB expression in the brain of DIO and ob/ob mice were also increased; this increase was related to the upregulation of SOCS3 and decreased phosphorylated STAT3, which decreased leptin sensitivity in the brain. PPB decreased inflammation in the brain, restored leptin sensitivity, and decreased food intake and weight gain in both DIO and ob/ob mice.

scholarly journals Enhanced brain angiogenesis in chronic cerebral hypoperfusion after administration of plasmid human vascular endothelial growth factor in combination with indirect vasoreconstructive surgery

2005 ◽  
Vol 103 (5) ◽  
pp. 882-890 ◽  
Author(s):  
Noboru Kusaka ◽  
Kenji Sugiu ◽  
Koji Tokunaga ◽  
Atsushi Katsumata ◽  
Ayumi Nishida ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Control Group ◽  
Vascular Endothelial ◽  
Content Type ◽  
Endothelial Growth Factor ◽  
The Brain ◽  
Brain Angiogenesis ◽  
Fine Print

Object. Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. The conceptual basis for therapeutic angiogenesis after plasmid human VEGF gene (phVEGF) transfer has been established in patients presenting with limb ischemia and myocardial infarction. The authors hypothesized that overexpression of VEGF using a gene transfer method combined with indirect vasoreconstruction might induce effective brain angiogenesis in chronic cerebral hypoperfusion, leading to prevention of ischemic attacks. Methods. A chronic cerebral hypoperfusion model induced by permanent ligation of both common carotid arteries in rats was used in this investigation. Seven days after induction of cerebral hypoperfusion, encephalomyosynangiosis (EMS) and phVEGF administration in the temporal muscle were performed. Fourteen days after treatment, the VEGF gene therapy group displayed numbers and areas of capillary vessels in temporal muscles that were 2.2 and 2.5 times greater, respectively, in comparison with the control group. In the brain, the number and area of capillary vessels in the group treated with the VEGF gene were 1.5 and 1.8 times greater, respectively, relative to the control group. Conclusions. In rat models of chronic cerebral hypoperfusion, administration of phVEGF combined with indirect vasoreconstructive surgery significantly increased capillary density in the brain. The authors' results indicate that administration of phVEGF may be an effective therapy in patients with chronic cerebral hypoperfusion, such as those with moyamoya disease.

Altered expression of neurofilament 200 and amyloid-β peptide (1–40) in a rat model of chronic cerebral hypoperfusion

2014 ◽  
Vol 36 (5) ◽  
pp. 707-712 ◽  
Author(s):  
Weihua Liang ◽  
Weiwei Zhang ◽  
Shifu Zhao ◽  
Qianning Li ◽  
Hua Liang ◽  
...  
Keyword(s):  
Rat Model ◽  
Amyloid Β ◽  
Chronic Cerebral Hypoperfusion ◽  
Cerebral Hypoperfusion ◽  
Amyloid Β Peptide ◽  
Altered Expression ◽  
Neurofilament 200

scholarly journals Estrogen receptor α phosphorylated at Ser216 confers inflammatory function to mouse microglia

2019 ◽  
Author(s):  
Sawako Shindo ◽  
Shih-Heng Chen ◽  
Saki Gotoh ◽  
Kosuke Yokobori ◽  
Hao Hu ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Inflammatory Cytokines ◽  
Estrogen Receptor Α ◽  
Microglia Activation ◽  
Immune Functions ◽  
Protein Levels ◽  
Brain Extracts ◽  
Anti Inflammatory ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Abstract Background Estrogen has been suggested to regulate anti-inflammatory signaling in brain microglia through estrogen receptor α (ERα), the only resident immune cells of the brain. The mechanism of how ERα regulates is not well understood. Previously, ERα is phosphorylated at Ser216 in mouse neutrophils, regulating their infiltration into the uterus. Therefore, ERα has now been examined as to its phosphorylation in microglia to regulate their inflammatory functions.MethodsAn antibody against an anti-phospho-S216 peptide of ERα (αP-S216) was used for double immunofluorescence staining to detect to ERα in cultured microglia. A knock-in (KI) mouse line bearing the phosphorylation-blocked ERα mutation S216A (ERα KI) was generated to examine whether this phosphorylation regulate immune functions of microglia.ResultsPhosphorylated ERα at Ser216 was present in microglia but not astrocytes. Staining with an anti-Iba-1 antibody showed that microglia activation was augmented in substantial nigra of ERα KI brains. Lipopolysaccharide (LPS) treatments aggravated microglia activation in ERα KI brains, pro-inflammatory cytokines were increased while anti-inflammatory cytokines were decreased at mRNA and protein levels in whole brain extracts. These increases and decreases of cytokine proteins were also observed in LPS-treated microglia cultured from brains of ERα KI neonates. FACS analysis revealed that ERα KI mutation increased number of IL-6 producing microglia and apoptosis. ERα KI mice decreased motor connection ability in Rotarod tests.ConclusionsBlocking of Ser216 phosphorylation aggravated microglia activation and inflammation of mouse brain, thus confirming that phosphorylated ERα exerts anti-inflammatory functions. ERα KI mice enable us to further investigate the mechanism by which phosphorylated ERα regulates brain immunity and inflammation.

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