Adamantinomatous Craniopharyngioma Cyst Fluid can Trigger Inflammatory Activation of Microglia to Damage the Hypothalamic Neurons by Inducing the Production of β-Amyloid

2021 ◽  
Author(s):  
Yilamujiang Ainiwan ◽  
Yiguang Chen ◽  
Chaofu Mao ◽  
Junxiang Peng ◽  
Siyuan Chen ◽  
...  
Keyword(s):  
Animal Model ◽  
Neurodegenerative Diseases ◽  
Cyst Fluid ◽  
Cellular Interaction ◽  
Hypothalamic Neurons ◽  
Cystic Fluid ◽  
Inflammatory Activation ◽  
Hypothalamic Injury ◽  
Β Amyloid ◽  
Adamantinomatous Craniopharyngioma

Abstract Introduction: The mechanism by which adamantinomatous craniopharyngioma (ACP) damages the hypothalamus is still unclear. Cyst fluid rich in lipids and inflammatory factors is a characteristic pathological manifestation of ACP and may play a very important role in hypothalamic injury caused by tumors. Objective: To construct a reliable animal model of ACP cyst fluid-induced hypothalamic injury and explore the specific mechanism of hypothalamic injury caused by cyst fluid. Methods: An animal model was establish by injecting human ACP cyst fluid into the bilateral hypothalamus of mice . ScRNA-seq was performed on the mice hypothalamus and on an ACP sample to obtain a complete gene expression profile for analysis. Data verification was performed through pathological means. Results: ACP cystic fluid caused growth retardation and an increased obesity index in mice, affected the expression of the Npy, Fgfr2, Rnpc3, Sst, and Pcsk1n genes that regulate growth and energy metabolism in hypothalamic neurons, and enhanced the cellular interaction of Agrp-Mc3r. ACP cystic fluid significantly caused inflammatory activation of hypothalamic microglia. The cellular interaction of CD74-APP is significantly strengthened between inflammatory-activated microglia and hypothalamic neurons. Beta-amyloid, a marker of neurodegenerative diseases, was deposited in the ACP tumor tissues and in the hypothalamus of mice injected with ACP cyst fluid. Conclusion: In this study, a novel animal model of ACP cystic fluid-hypothalamic injury was established. For the first time, it was found that ACP cystic fluid can trigger inflammatory activation of microglia to damage the hypothalamus, which may be related to the upregulation of the CD74-APP interaction and deposition of β-amyloid, implying that there may be a similar mechanism between ACP cystic fluid damage to the hypothalamus and neurodegenerative diseases.

scholarly journals Effect of various extracts of Tabernaemontana divaricata on haloperidol induced catalepsy in rats

2014 ◽  
Vol 3 (3) ◽  
pp. 240-242 ◽  
Author(s):  
Chanchal N. Raj ◽  
A. Balasubramaniam ◽  
Sayyed Nadeem
Keyword(s):  
Animal Model ◽  
Substantia Nigra ◽  
Neurodegenerative Diseases ◽  
Pharmaceutical Journal ◽  
Dopamine Neurons ◽  
Substantia Nigra Pars Compacta ◽  
Selective Loss ◽  
Tabernaemontana Divaricata ◽  
Medicinal Use ◽  
Different Doses

Parkinson’s disease (PD) is one of the neurodegenerative diseases with selective loss of dopamine neurons of the substantia nigra pars compacta. In the present study, anti-cataleptic activity of Tabernaemontana divaricata leaves extracts viz. aqueous and ethanolic at different doses (50, 100 and 150 mg/kg i.p.) were studied using haloperidol (1 mg/kg, i.p.) induced catalepsy in rats which is a useful animal model for screening drugs for Parkinson’s disease. Both the extracts were found to reduce catalepsy significantly (P<0.001) as compared to the haloperidol treated rats showing greater effect at 150 mg/kg i.p. dose. Thus the present study reveals the anti-cataleptic activity of Tabernaemontana divaricata evaluating the traditional folklore medicinal use of the plant.DOI: http://dx.doi.org/10.3329/icpj.v3i3.17891 International Current Pharmaceutical Journal, February 2014, 3(3): 240-242

scholarly journals Ablating Aspiration Needle Tract Prior to Microwave Ablation Can Improve Therapeutic Outcomes for Predominantly Cystic Thyroid Nodules

2021 ◽  
Vol 12 ◽  
Author(s):  
Haizhen Yang ◽  
Yanwei Chen ◽  
Baoding Chen ◽  
Shuangshuang Zhao ◽  
Zheng Zhang ◽  
...  
Keyword(s):  
Postoperative Complications ◽  
Microwave Ablation ◽  
Thyroid Nodules ◽  
Cyst Fluid ◽  
Cystic Fluid ◽  
Needle Tract ◽  
Intracystic Hemorrhage ◽  
Group A ◽  
Hospital Stays ◽  
Group B

PurposeTo investigate whether ablating the aspiration needle tract could improve the safety and efficacy of ultrasound-guided microwave ablation (MWA) for predominantly cystic thyroid nodules.Materials and MethodsThis retrospective study evaluated 41 predominantly cystic thyroid nodules that underwent MWA between June 2017 and August 2019. The nodules were stratified by different procedures into two groups: the aspiration needle tract was ablated before cyst fluid aspiration and MWA when treating 26 nodules in Group A, while the other 15 nodules in Group B underwent MWA directly after cyst fluid aspiration. Baseline characteristics, intervention time, hospital stays, nodules with intraoperative intracystic hemorrhage, and postoperative complications were compared between the two groups. Volume, volume reduction rate (VRR), compressive score (CS), and aesthetic score (AS) were evaluated during follow-up.ResultsBoth groups achieved decreases in volume, CS, and AS, as well as an increase in VRR. The volumes and VRRs in Group A at 1, 3, 6, and 12 months were significantly smaller and greater than those in Group B (p &lt; 0.001). The incidence of intraoperative intracystic hemorrhage in Group A was significantly lower than that in Group B (p=0.035). Compared to Group B, hospital stays were much shorter in Group A (p=0.040). There were no significant differences in intervention time, cystic fluid volume or postoperative complications.ConclusionAspiration needle tract ablation dramatically reduces the incidence of intraoperative intracystic hemorrhage and markedly improves the efficacy of MWA for predominantly cystic thyroid nodules.

scholarly journals PROTECTIVE EFFECT OF IRIS GERMANICA L. IN Β-AMYLOID-INDUCED ANIMAL MODEL OF ALZHEIMER’S DISEASE

2017 ◽  
Vol 14 (4) ◽  
pp. 140-148 ◽  
Author(s):  
Mona Borhani ◽  
Mohammad Sharifzadeh ◽  
Mohammad Hosein Farzaei ◽  
Zahra Narimani ◽  
Fatemeh Sabbaghziarani ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Protective Effect ◽  
Model Of Alzheimer’S Disease ◽  
Iris Germanica ◽  
Β Amyloid

β-Amyloid protein-induced Alzheimer's disease animal model

1994 ◽  
Vol 170 (1) ◽  
pp. 63-66 ◽  
Author(s):  
Atsumi Nitta ◽  
Akio Itoh ◽  
Takaaki Hasegawa ◽  
Toshitaka Nabeshima
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Amyloid Protein ◽  
Β Amyloid

scholarly journals Adamantinomatous craniopharyngioma associated with a compromised blood–brain barrier: patient series

2021 ◽  
Vol 1 (19) ◽  
Author(s):  
Eric W. Prince ◽  
Lindsey M. Hoffman ◽  
Trinka Vijmasi ◽  
Kathleen Dorris ◽  
Jennifer A. McWilliams ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Tumor Tissue ◽  
Pediatric Brain Tumor ◽  
Cyst Fluid ◽  
Brain Barrier ◽  
Enzyme Linked Immunosorbent Assay ◽  
Blood Brain ◽  
Humanized Monoclonal Antibody ◽  
Interleukin 6 Receptor ◽  
Adamantinomatous Craniopharyngioma

BACKGROUND Adamantinomatous craniopharyngioma (ACP) is a highly morbid adult and pediatric brain tumor derived from epithelial remnants of the craniopharyngeal canal (Rathke’s pouch), which gives rise to the anterior pituitary gland. Standard therapy includes maximal safe resection with or without radiation therapy. Systemic antitumor therapy remains elusive. Immune-related paracrine signaling involving the interleukin-6 receptor (IL-6R) may contribute to ACP pathogenesis. Tocilizumab, a recombinant humanized monoclonal antibody against IL-6R, is approved by the US Food and Drug Administration but does not cross an intact blood–brain barrier. OBSERVATIONS In a phase 0 trial design, a single dose of tocilizumab was delivered intravenously before clinically indicated surgical intervention in 3 children with ACP. The presence of tocilizumab was assayed in plasma, tumor tissue, tumor cyst fluid, and cerebrospinal fluid (n = 1) using a novel enzyme-linked immunosorbent assay. Tocilizumab reached ACP tumor tissue and/or cyst fluid after one systemic dose in every patient. LESSONS This finding helps explain extant data that indicate tocilizumab may contribute to ACP therapy. It further indicates that ACP does not reside behind an intact blood–brain barrier, dramatically broadening the range of potential antitumor therapies against this tumor. This has substantial implications for the design of future clinical trials for novel therapies against ACP in both children and adults.

scholarly journals Transmissible Endosomal Intoxication: A Balance between Exosomes and Lysosomes at the Basis of Intercellular Amyloid Propagation

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 272
Author(s):  
Anaïs Bécot ◽  
Charlotte Volgers ◽  
Guillaume van Niel
Keyword(s):  
Amyloid Precursor Protein ◽  
Neurodegenerative Diseases ◽  
Multivesicular Body ◽  
Precursor Protein ◽  
Aβ Peptides ◽  
Amyloid Aβ ◽  
Β Amyloid ◽  
Novel Concept ◽  
The Brain

In Alzheimer′s disease (AD), endolysosomal dysfunctions are amongst the earliest cellular features to appear. Each organelle of the endolysosomal system, from the multivesicular body (MVB) to the lysosome, contributes to the homeostasis of amyloid precursor protein (APP) cleavage products including β-amyloid (Aβ) peptides. Hence, this review will attempt to disentangle how changes in the endolysosomal system cumulate to the generation of toxic amyloid species and hamper their degradation. We highlight that the formation of MVBs and the generation of amyloid species are closely linked and describe how the molecular machineries acting at MVBs determine the generation and sorting of APP cleavage products towards their degradation or release in association with exosomes. In particular, we will focus on AD-related distortions of the endolysomal system that divert it from its degradative function to favour the release of exosomes and associated amyloid species. We propose here that such an imbalance transposed at the brain scale poses a novel concept of transmissible endosomal intoxication (TEI). This TEI would initiate a self-perpetuating transmission of endosomal dysfunction between cells that would support the propagation of amyloid species in neurodegenerative diseases.

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