scholarly journals Repression of the Glucocorticoid Receptor Aggravates Acute Ischemic Brain Injuries in Adult Mice

2018 ◽  
Vol 19 (8) ◽  
pp. 2428 ◽  
Author(s):  
Yong Li ◽  
Lei Huang ◽  
Qingyi Ma ◽  
Katherine Concepcion ◽  
Minwoo Song ◽  
...  
Keyword(s):  
Glucocorticoid Receptor ◽  
Brain Injuries ◽  
Expression Profiles ◽  
Control Group ◽  
Ischemic Brain ◽  
Expression Levels ◽  
Adult Mice ◽  
Neurobehavioral Deficits ◽  
The Brain

Strokes are one of the leading causes of mortality and chronic morbidity in the world, yet with only limited successful interventions available at present. Our previous studies revealed the potential role of the glucocorticoid receptor (GR) in the pathogenesis of neonatal hypoxic-ischemic encephalopathy (HIE). In the present study, we investigate the effect of GR knockdown on acute ischemic brain injuries in a model of focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) in adult male CD1 mice. GR siRNAs and the negative control were administered via intracerebroventricular (i.c.v.) injection 48 h prior to MCAO. The cerebral infarction volume and neurobehavioral deficits were determined 48 h after MCAO. RT-qPCR was employed to assess the inflammation-related gene expression profiles in the brain before and after MCAO. Western Blotting was used to evaluate the expression levels of GR, the mineralocorticoid receptor (MR) and the brain-derived neurotrophic factor/tropomyosin receptor kinase B (BDNF/TrkB) signaling. The siRNAs treatment decreased GR, but not MR, protein expression, and significantly enhanced expression levels of pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) in the brain. Of interest, GR knockdown suppressed BDNF/TrkB signaling in adult mice brains. Importantly, GR siRNA pretreatment significantly increased the infarction size and exacerbated the neurobehavioral deficits induced by MCAO in comparison to the control group. Thus, the present study demonstrates the important role of GR in the regulation of the inflammatory responses and neurotrophic BDNF/TrkB signaling pathway in acute ischemic brain injuries in adult mice, revealing a new insight into the pathogenesis and therapeutic potential in acute ischemic strokes.

scholarly journals Violation in the axis of the "microbiota of the digestive tract-brain" under conditions of ischemia-reperfusion of the brain (literature review)

2021 ◽  
Vol 11 (5) ◽  
pp. 325-332
Author(s):  
O. Tkachuk ◽  
S. Tkachuk ◽  
M. Povar ◽  
O. Denysenko ◽  
V. Shtefaniuk
Keyword(s):  
Literature Review ◽  
Intestinal Microbiota ◽  
Brain Injuries ◽  
Ischemia Reperfusion ◽  
T Cell Homeostasis ◽  
Ischemic Brain ◽  
Intestinal Lymphocytes ◽  
And Migration ◽  
The Brain

The aim of the study is to analyze current views concerning interrelations between the state of intestinal microbiota and the course of ischemic-reperfusion brain injury.   Conclusion. Literary data are indicative of disputable scientific opinions existing nowadays concerning the role of dysbacteriosis (neuroprotective or neurodegenerative) in the course of ischemic brain injuries. Meanwhile, the studies are in common concerning the evidenced role of the intestinal microbiota in disturbances of T-cell homeostasis, ratio changes of their Treg-Th17 subpopulations, and migration of intestinal lymphocytes to the ischemic brain.  

scholarly journals Role of Nitric Oxide in Regulation of Brain Stem Circulation during Hypotension

1997 ◽  
Vol 17 (10) ◽  
pp. 1089-1096 ◽  
Author(s):  
Kazunori Toyoda ◽  
Kenichiro Fujii ◽  
Setsuro Ibayashi ◽  
Tetsuhiko Nagao ◽  
Takanari Kitazono ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Brain Stem ◽  
Topical Application ◽  
Basilar Artery ◽  
Group Versus ◽  
Control Group ◽  
Cranial Window ◽  
Severe Hypotension ◽  
The Brain

We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10−5 mol/L and 10−4 mol/L Nω-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10−5 mol/L and 60 to 75 mm Hg in the 10−4 mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 ± 8% in the 10−5 mol/L and 12 ± 5% in the 10−4 mol/L L-NNA group versus 34 ± 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10−5 mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.

scholarly journals Identification of Type II Interferon Receptors in Geese: Gene Structure, Phylogenetic Analysis, and Expression Patterns

2015 ◽  
Vol 2015 ◽  
pp. 1-14
Author(s):  
Hao Zhou ◽  
Shun Chen ◽  
Yulin Qi ◽  
Qin Zhou ◽  
Mingshu Wang ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Expression Patterns ◽  
Harderian Gland ◽  
Distribution Analysis ◽  
Expression Levels ◽  
Age Related ◽  
Cecal Tonsil ◽  
Immune Tissues ◽  
First Time

Interferonγreceptor 1 (IFNGR1) and IFNGR2 are two cell membrane molecules belonging to class II cytokines, which play important roles in the IFN-mediated antiviral signaling pathway. Here, goose IFNGR1 and IFNGR2 were cloned and identified for the first time. Tissue distribution analysis revealed that relatively high levels of goose IFNγmRNA transcripts were detected in immune tissues, including the harderian gland, cecal tonsil, cecum, and thymus. Relatively high expression levels of both IFNGR1 and IFNGR2 were detected in the cecal tonsil, which implicated an important role of IFNγin the secondary immune system of geese. No specific correlation between IFNγ, IFNGR1, and IFNGR2 expression levels was observed in the same tissues of healthy geese. IFNγand its cognate receptors showed different expression profiles, although they appeared to maintain a relatively balanced state. Furthermore, the agonist R848 led to the upregulation of goose IFNγbut did not affect the expression of goose IFNGR1 or IFNGR2. In summary, trends in expression of goose IFNγand its cognate receptors showed tissue specificity, as well as an age-related dependency. These findings may help us to better understand the age-related susceptibility to pathogens in birds.

scholarly journals New cerebrovascular agent with hypotensive activity

2019 ◽  
Vol 5 (2) ◽  
pp. 71-77
Author(s):  
Galina A. Kim ◽  
Tamara S. Gan’shina ◽  
Elena V. Kurza ◽  
Ilya N. Kurdyumov ◽  
Denis V. Maslennikov ◽  
...  
Keyword(s):  
Blood Flow ◽  
Antihypertensive Agent ◽  
Brain Injuries ◽  
Cerebrovascular Disorders ◽  
Male Rats ◽  
Hypotensive Activity ◽  
Duration Of Action ◽  
Ischemic Brain ◽  
Cerebrovascular Activity ◽  
The Brain

Introduction: In cerebrovascular disorders, special attention is paid to a hypertensive cerebrovascular crisis, which combines a vascular injury of the brain and hypertension. The paper studies the cerebrovascular properties of the calcium channel blocker of S-Amlodipine nicotinate antihypertensive agent. Materials and methods: Tests were performed on 96 nonlinear male rats, measuring local blood flow in the cerebral cortex in 36 awake animals, using a laser Doppler flowmeter. Cerebral circulation was recorded in the animals when modeling ischemic and hemorrhagic brain injuries. Results and discussion: S-Amlodipine nicotinate (0.1 mg/kg i/v) shows a pronounced cerebrovascular activity in the models of ischemic and hemorrhagic injuries of the brain. In terms of the vasodilating effect in ischemic brain injury, the drug is comparable to mexidol, nimodipine, picamilon, but is superior to nimodipine and picamilon in terms of duration of action, and in the model of hemorrhagic stroke, S-Amlodipine nicotinate is superior to nimodipine and is comparable to picamilon and mexidol. The analysis of the mechanism of action of the agent revealed the participation of GABA A-receptors in the implementation of cerebrovascular properties of the agent. Conclusion: Significant cerebrovascular activity of S-Amlodipine nicotinate (0.1 mg/kg i/v) antihypertensive agent was revealed. The presence of GABAergic mechanism on cerebral blood flow in the agent action along with blockade of slow calcium channels ensures its high efficacy in treatment of both ischemic and hemorrhagic brain injuries.

scholarly journals Role of Acupuncture in the Management of Severe Acquired Brain Injuries (sABIs)

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Loredana Cavalli ◽  
Lucia Briscese ◽  
Tiziana Cavalli ◽  
Paolo Andre ◽  
Maria Chiara Carboncini
Keyword(s):  
Brain Injuries ◽  
Neuronal Regeneration ◽  
Asian Countries ◽  
Rehabilitative Treatment ◽  
Beneficial Effects ◽  
Nervous System Activity ◽  
Neurologic Disorders ◽  
Central Nervous System Activity ◽  
The Brain

Acupuncture therapy has been used to treat several disorders in Asian countries and its use is increasing in Western countries as well. Current literature assessed the safety and efficacy of acupuncture in the acute management and rehabilitation of patients with neurologic disorders. In this paper, the role of acupuncture in the treatment of acute severe acquired brain injuries is described, acting on neuroinflammation, intracranial oedema, oxidative stress, and neuronal regeneration. Moreover, beneficial effects of acupuncture on subacute phase and chronic outcomes have been reported in controlling the imbalance of IGF-1 hormone and in decreasing spasticity, pain, and the incidence of neurovegetative crisis. Moreover, acupuncture may have a positive action on the arousal recovery. Further work is needed to understand the effects of specific acupoints on the brain. Allegedly concurrent neurophysiological measurements (e.g., EEG) may help in studying acupuncture-related changes in central nervous system activity and determining its potential as an add-on rehabilitative treatment for patients with consciousness disorders.

ATI-2341 Trifluoroacetic Acid (TFA) Promotes Menstrual Blood-Derived Mesenchymal Stem Cell Recruitment and Enhances Uterine Repair Through Gi Pathway in Asherman’s Syndrome

2022 ◽  
Vol 12 (3) ◽  
pp. 506-513
Author(s):  
Ying Lv ◽  
Liyan Ye ◽  
Xiujuan Zheng
Keyword(s):  
Menstrual Blood ◽  
Control Group ◽  
Dependent Manner ◽  
Asherman’S Syndrome ◽  
Expression Levels ◽  
Endometrial Cells ◽  
Injury Model ◽  
Recruitment Effect ◽  
Dose Dependent

This study aimed to explore the role of ATI-2341 in Asherman’s syndrome and its impact on menstrual blood-derived mesenchymal stem cells (MenSCs). Following establishment of endometrial injury model, MenSCs were extracted from rats and cultured. They were treated with ATI-2341 TFA at different concentrations (10 ng/mL, 50 ng/mL, 100 ng/mL) and MenSCs treated without ATI-2341 TFA were taken as controls. Flow cytometry was conducted to detect the cell cycle. MTT was carried out to evaluate proliferation of endometrial cells. The expression levels of MMP-9, TIMP-1, CK, and VIM were determined with staining used to reflect morphology of endometrium. Administration with ATI-2341 TFA resulted in decreased expression of MMP-9 and increased expression of TIMP-1 in a dose-dependent manner. Of note, the increase of ATI-2341 TFA concentration was accompanied with elevated cell proliferation rate, increased number of glands in the endometrium, and decreased fibrosis area. As treated with 100 ng/mL ATI-2341 TFA, the cells exhibited more glands than that under other concentrations with uniformly arranged glands and lowest expression levels of CK and VIM, control group had plenty of blue-stained collagen fibers in the intima and least amount of glands. ATI-2341 TFA 100 ng/mL induced endometrial epithelial recruitment effect on MenSCs and promoted endometrial repair more significantly than Gi-3 pathway agonists. Collectively, ATI-2341 TFA enhances MenSC recruitment and facilitates endometrial epithelial cells proliferation and the repair of uterine damage in Asherman’s syndrome through Gi pathway. These findings provide a\ novel insight into the MenSC-based treatment against Asherman’s syndrome and deserve further investigation.

scholarly journals Granulosa-Lutein Cell Sirtuin Gene Expression Profiles Differ between Normal Donors and Infertile Women

2019 ◽  
Vol 21 (1) ◽  
pp. 295
Author(s):  
Rebeca González-Fernández ◽  
Rita Martín-Ramírez ◽  
Deborah Rotoli ◽  
Jairo Hernández ◽  
Frederick Naftolin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Localization ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Cellular Protein ◽  
Control Group ◽  
Poor Responders ◽  
Male Factor ◽  
Expression Levels ◽  
Genes Expression

Sirtuins are a family of deacetylases that modify structural proteins, metabolic enzymes, and histones to change cellular protein localization and function. In mammals, there are seven sirtuins involved in processes like oxidative stress or metabolic homeostasis associated with aging, degeneration or cancer. We studied gene expression of sirtuins by qRT-PCR in human mural granulosa-lutein cells (hGL) from IVF patients in different infertility diagnostic groups and in oocyte donors (OD; control group). Study 1: sirtuins genes’ expression levels and correlations with age and IVF parameters in women with no ovarian factor. We found significantly higher expression levels of SIRT1, SIRT2 and SIRT5 in patients ≥40 years old than in OD and in women between 27 and 39 years old with tubal or male factor, and no ovarian factor (NOF). Only SIRT2, SIRT5 and SIRT7 expression correlated with age. Study 2: sirtuin genes’ expression in women poor responders (PR), endometriosis (EM) and polycystic ovarian syndrome. Compared to NOF controls, we found higher SIRT2 gene expression in all diagnostic groups while SIRT3, SIRT5, SIRT6 and SIRT7 expression were higher only in PR. Related to clinical parameters SIRT1, SIRT6 and SIRT7 correlate positively with FSH and LH doses administered in EM patients. The number of mature oocytes retrieved in PR is positively correlated with the expression levels of SIRT3, SIRT4 and SIRT5. These data suggest that cellular physiopathology in PR’s follicle may be associated with cumulative DNA damage, indicating that further studies are necessary.

scholarly journals The Role of Magnetic Resonance Spectroscopy in Evaluating the Rate of Brain Metabolic Variations in Chemical Veterans with Respiratory Problem In Comparison To Control Group

2018 ◽  
Vol 6 (12) ◽  
pp. 2348-2353
Author(s):  
Seyyed Arash Mahdawy ◽  
Babak Shekarchi ◽  
Mahshid Zaman
Keyword(s):  
Magnetic Resonance ◽  
Magnetic Resonance Spectroscopy ◽  
Brain Injuries ◽  
Sulfur Mustard ◽  
Complete Information ◽  
Brain Dysfunction ◽  
Control Group ◽  
Resonance Spectroscopy ◽  
Metabolic Properties ◽  
The Brain

BACKGROUND:  During the eight years of the imposed war, Iraq used various chemical agents such as sulfur mustard and nerve agents (mainly tabun and sometimes soman) on Iran's soldiers. Using information obtained from specialist sequences and analysing information obtained from magnetic resonance imaging (MRI) in a susceptibility weighted imaging (SWI) sequence and magnetic resonance spectroscopy (MRS) provides valuable information on continuation of treatment and identifying functional disorders. AIM: The objective of this research was to evaluate the rate of metabolic variations in chemically injured veterans based on chemical neuromarkers using the chemical sequence MRS, which would help patients and physicians in terms of time, economics, and selection of appropriate therapeutic methods, so if the can physician can get complete information about the metabolic properties of the brain through paraclinical (especially MRI) tools before treatment, he might change his treatment program to reduce the complications caused by it. METHODOLOGY: In this research, 40 chemically injured veterans with brain dysfunction admitted to the screening centre for MRI with specialized MRS sequence participated. Accordingly, we examined the rate of brain metabolic variations about the level of neuromarkers and evaluated the relationship between the level of neuromarkers and brain damages. RESULTS: The results of this research revealed that while the demographic characteristics such as age of the two groups of chemically injured veterans and control was similar, only the median of the NAA/Cr (N-acetylaspartate to creatine ratio) ratio in PONS of chemically injured patients was significantly lower than that of the control group, and this ratio was similar in other parts of the brain in two groups. The results also showed that the ratio of NAA to total choline and Cr was similar in all parts of the brain in two groups. CONCLUSION: Based on the research results, using the MR (Magnetic Resonance) spectroscopy device and determination of the value and ratio of markers such as creatinine and N-acetylaspartate and choline, the brain injuries of chemically injured veterans can be examined. By conducting further studies and larger sample size, the brain damages in veterans can be diagnosed early, which would be a great contribution in their treatment.

Molecular Mechanisms of Ischemic Cerebral Edema: Role of Electroneutral Ion Transport

Physiology ◽  
2009 ◽  
Vol 24 (4) ◽  
pp. 257-265 ◽  
Author(s):  
Kristopher T. Kahle ◽  
J. Marc Simard ◽  
Kevin J. Staley ◽  
Brian V. Nahed ◽  
Pamela S. Jones ◽  
...  
Keyword(s):  
Cerebral Edema ◽  
Molecular Mechanisms ◽  
Cell Volume Regulation ◽  
Cell Swelling ◽  
Ischemic Brain Injury ◽  
Edema Formation ◽  
Ischemic Brain ◽  
The Brain ◽  
Permeability Alterations

The brain achieves homeostasis of its intracellular and extracellular fluids by precisely regulating the transport of solute and water across its major cellular barriers: endothelia of the blood-brain barrier (BBB), choroid plexus epithelia, and neuroglial cell membranes. Cerebral edema, the pathological accumulation of fluid in the brain’s intracellular and extracellular spaces, is a major cause of morbidity and mortality following stroke and other forms of ischemic brain injury. Until recently, mechanisms of cerebral edema formation have been obscure; consequently, its treatment has been empiric and suboptimal. Here, we provide a paradigm for understanding ischemic cerebral edema, showing that its molecular pathogenesis is a complex yet step-wise process that results largely from impaired astrocytic cell volume regulation and permeability alterations in the cerebral microvasculature, both of which arise from pathological changes in the activities of specific ion channels and transporters. Recent data has implicated the bumetanide-sensitive NKCC1, an electroneutral cotransporter expressed in astrocytes and the BBB, in cerebral edema formation in several different rodent models of stroke. Pharmacological inhibition or genetic deficiency of NKCC1 decreases ischemia-induced cell swelling, BBB breakdown, cerebral edema, and neurotoxicity. Combination pharmacological strategies that include NKCC1 as a target might thus prove beneficial for the treatment of ischemic, and potentially other types of, cerebral edema.

Cytokine expression profiles of patients with acute myelogenous leukemia (AML) and non-Hodgkin lymphoma (NHL) detected by multiplex assay

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18530-18530
Author(s):  
V. B. Reddy ◽  
D. K. Oelschlager ◽  
J. S. Nolan ◽  
K. L. Taylor ◽  
J. Post ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Recovery Phase ◽  
Cytokine Expression ◽  
Multiplex Assay ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Serum Samples ◽  
Expression Levels ◽  
Significant Difference ◽  
Low Levels

18530 Background: To determine the cytokine expression profiles of patients with AML and NHL using a sensitive bead-based Luminex multiplex assay in a routine clinical diagnostic setting. Methods: Blood (plasma/serum) samples were collected from ten AML and five NHL patients. Six control samples from patients diagnosed as non-neoplastic/non-autoimmune/non-inflammatory were also analyzed for comparison. All samples were frozen prior to analysis. Using a bead-based Luminex assay (Human Cytokine 8-Plex Assay, Bio- Rad, Hercules, CA) we analyzed these samples for a panel of cytokines (IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma, and TNF-alpha). This assay uses polystyrene microspheres, which provides simultaneous quantitation of these cytokines in a single sample. The expression levels were presented in picograms/mL. Average values for each of these markers were obtained for each group of patients (AML versus NHL versus Controls), and their expression levels were compared using χ2 analysis. Results: Overall, there was a significant difference in the expression profiles of all these cytokines among three patients groups (χ2, P < 0.001). All cytokines were consistently expressed at low levels in NHL patients as compared to control group. However, the levels of IL-6 and IL-8 were increased by 2.7 and 5.8 times, respectively in AML patients as compared to controls. Conclusions: The low levels of cytokines in NHL and AML patients suggest suppressed immune system in these two disease conditions; however, these findings warrant further studies to explore the underlying mechanisms for the increased levels of IL-6 and IL-8 in AML patients. Currently, studies are in progress to compare the levels of cytokines measured by Luminiex assay in different stages of leukemias and lymphomas (initial, post treatment and recovery phase etc.). These studies are partially funded by grants from the National Institute of Health/National Cancer Institute (RO1-CA98932–01 and U24-CA086359). No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document