scholarly journals Analytical methods for assessing changes induced by gamma exposure in an animal model

2020 ◽  
Vol 66 (12) ◽  
pp. 1651-1656
Author(s):  
Matheus F. Soares Mingote ◽  
Tarcísio P.R. Campos ◽  
Rodinei Augusti ◽  
Geovanni D. Cassali

SUMMARY OBJECTIVE: Ionizing radiation can cause radio-induced changes in the cellular metabolome due to the breakdown of DNA bonds. Our goal was to find the early tissue response to radiation exposure supported by distinct analytical methods. METHODS: Histological analyses were performed on the organs extracted from rats to search for microscopic changes. The histological slides stained with hematoxyline-eosin (HE) were analyzed in magnification (40x). Subsequently, the tissues were subjected to mass spectrometry that allowed molecular analysis and DESI-MSI that generated the molecular image of lipids, assessing changes in intensities, especially in the brain. RESULTS: The histological analysis found nonspecific inflammatory changes; no areas of fibrosis, necrosis, or apoptosis were identified, suggesting non-morphological tissue alterations. However, the DESI-MSI images of brain lipids allowed the observation of many radio-induced changes in the lipid's intensities. CONCLUSIONS: No early radio induced histological or mass weight changes in the radiation exposed rats could be observed at 5 Gy. However, early changes in the molecular level were observed in the DESI-MSI images of the brain lipids. The DESI-MSI method proved to be efficient and relevant, allowing a regional molecular analysis of the tissues, expanding a new field of study that is still in its infancy: radiometabolomics.

2016 ◽  
Vol 311 (1) ◽  
pp. R14-R23 ◽  
Author(s):  
Jessica Santollo ◽  
Anikó Marshall ◽  
Kathleen S. Curtis ◽  
Robert C. Speth ◽  
Stewart D. Clark ◽  
...  

Estradiol (E2) decreases both water and saline intakes by female rats. The ERα and ERβ subtypes are expressed in areas of the brain that control fluid intake; however, the role that these receptors play in E2's antidipsogenic and antinatriorexigenic effects have not been examined. Accordingly, we tested the hypothesis that activation of ERα and ERβ decreases water and saline intakes by female rats. We found a divergence in E2's inhibitory effect on intake: activation of ERα decreased water intake, whereas activation of ERβ decreased saline intake. E2 decreases expression of the angiotensin II type 1 receptor (AT1R), a receptor with known relevance to water and salt intakes, in multiple areas of the brain where ERα and ERβ are differentially expressed. Therefore, we tested for agonist-induced changes in AT1R mRNA expression by RT-PCR and protein expression by analyzing receptor binding to test the hypothesis that the divergent effects of these ER subtypes are mediated by region-specific changes in AT1R expression. Although we found no changes in AT1R mRNA or binding in areas of the brain known to control fluid intake associated with agonist treatment, the experimental results replicate and extend previous findings that body weight changes mediate alterations in AT1R expression in distinct brain regions. Together, the results reveal selective effects of ER subtypes on ingestive behaviors, advancing our understanding of E2's inhibitory role in the controls of fluid intake by female rats.


2020 ◽  
Vol 45 (2) ◽  
Author(s):  
Arpita Chakraborty ◽  
Samir Kumar Praharaj ◽  
R. V. Krishnananda Prabhu ◽  
M. Mukhyaprana Prabhu

AbstractBackgroundMore than half portion of the brain is formed by lipids. They play critical roles in maintaining the brain's structural and functional components. Any dysregulation in these brain lipids can lead to cognitive dysfunction which are associated with neurological disorders such as Alzheimer's disease, Parkinson's disease, schizophrenia, vascular dementia etc. Studies have linked lipids with cognitive impairment. But not much has been studied about the complex brain lipids which might play a pivotal role in cognitive impairment. This review aims to highlight the lipidomic profiles in patients with cognitive dysfunction.ResultsForty-five articles were reviewed. These studies show alterations in complex lipids such as sphingolipids, phospholipids, glycolipids and sterols in brain in various neurological disorders such as vascular dementia, Parkinson's and Alzheimer's disease. However, the classes of fatty acids in these lipids involved are different across studies.ConclusionsThere is a need for targeted lipidomics analysis, specifically including sphingolipids in patients with neurodegenerative disorders so as to improve diagnostics as well as management of these disorders.


2021 ◽  
Vol 66 (4) ◽  
pp. 18-24
Author(s):  
I. Ushakov ◽  
Vladimir Fyodorov

Purpose: Comparative assessment of radiation-induced changes in neurons of the cerebral cortex after a single and fractionated exposure to ionizing radiation in doses of 0.1 – 1.0 Gy. Material and methods. The study was carried out in compliance with the rules of bioethics on 180 white outbred male rats at the age of 4 months. by the beginning of the experiment, exposed to a single or fractionated exposure to γ-quanta of 60Co in total doses of 0.1; 0.2; 0.5 and 1.0 Gy. Neuromorphological and histochemical methods were used to assess morphometric and tinctorial parameters of nerve cells, as well as changes in the content of protein and nucleic acids in neurons in the early and late periods of the post-radiation period. Using one-way analysis of variance, a comparative assessment of neuromorphological indicators under various modes of radiation exposure is given. Results: In the control and irradiated animals throughout their life, undulating changes in the indicators of the state of the neurons of the brain occur with a gradual decrease by the end of the experiment. Despite a number of features of the dynamics of neuromorphological parameters, these irradiation regimes do not cause functionally significant changes in the neurons of the cortex. However, in some periods of the post-radiation period, the changes under the studied irradiation regimes were multidirectional and did not always correspond to age control. Significant differences in the response of neurons to these modes of radiation exposure in the sensory and motor areas of the cerebral cortex have not been established. Conclusion: No functionally significant radiation-induced changes in neurons were found either with single or fractionated irradiation. At the same time, different modes of irradiation in general caused the same type of changes in neurons. However, in some periods of observation, changes in neuromorphological parameters under the studied irradiation regimes were not unidirectional and differed from age control, which indicates a possible risk of disturbances in the functioning of the nervous system against the background of other harmful and dangerous factors.


2016 ◽  
Vol 17 (4) ◽  
pp. 434-438 ◽  
Author(s):  
Ritchell van Dams ◽  
Henry S. Park ◽  
Ahmed K. Alomari ◽  
Adele S. Ricciardi ◽  
Harini Rao ◽  
...  

This case report demonstrates that hypofractionated partial-brain radiation therapy with limited margins is a reasonable approach following gross tumor resection of Ewing sarcoma metastases to the brain. The patient presented with 2 intracranial metastases treated with gross-total resection followed by radiation therapy to 30 Gy in 5 fractions. The patient experienced symptomatic treatment-related inflammatory changes with resolution after receiving dexamethasone. He remains alive at 21 months of follow-up with no evidence of disease.


Neurosurgery ◽  
2011 ◽  
Vol 69 (4) ◽  
pp. 921-929 ◽  
Author(s):  
Richard W Hutchinson ◽  
Vince Mendenhall ◽  
Randolph M Abutin ◽  
Tim Muench ◽  
James Hart

Abstract BACKGROUND: Watertight repair of the dura is imperative after neurosurgical procedures involving the brain or spinal cord because inadequately treated leakage of cerebrospinal fluid (CSF) from punctured dura can have serious consequences such as meningitis, arachnoiditis, or epidural abscess. OBJECTIVE: To assess the efficacy of Evicel Fibrin Sealant (Human) to prevent CSF leakage using a 2.0-cm durotomy mongrel dog repair model and to compare the tissue response with Tisseel (a fibrin sealant) and Duraseal (a synthetic polyethylene glycol [PEG] hydrogel sealant). METHODS: The canine durotomy repair model was used. This well-characterized model assesses the ability of sealants to achieve intraoperative watertight seals of the dura mater, as well as long-term safety and efficacy. This study included 27 mongrel dogs and had a 28-day duration. RESULTS: The 3 sealants were 100% effective in preventing CSF leakage intraoperatively at 15 mm Hg. The 2 fibrin sealants were 100% effective in postoperative sealing; the PEG hydrogel was not. Microscopically, the tissue changes induced by Evicel at the durotomy site were similar in nature except for foamy macrophages seen only with the PEG hydrogel. The extent and severity of adhesions at 28 days were less with the fibrin sealants than with the PEG hydrogel. CONCLUSION: Evicel, a fibrin sealant, was safe and effective in achieving and maintaining a watertight seal of the dura. The performance of the fibrin sealants was similar to that of the synthetic PEG hydrogel sealant with the exception of a Duraseal seal, which leaked.


2021 ◽  
Vol 17 (5) ◽  
pp. e1008958
Author(s):  
Alan Eric Akil ◽  
Robert Rosenbaum ◽  
Krešimir Josić

The dynamics of local cortical networks are irregular, but correlated. Dynamic excitatory–inhibitory balance is a plausible mechanism that generates such irregular activity, but it remains unclear how balance is achieved and maintained in plastic neural networks. In particular, it is not fully understood how plasticity induced changes in the network affect balance, and in turn, how correlated, balanced activity impacts learning. How do the dynamics of balanced networks change under different plasticity rules? How does correlated spiking activity in recurrent networks change the evolution of weights, their eventual magnitude, and structure across the network? To address these questions, we develop a theory of spike–timing dependent plasticity in balanced networks. We show that balance can be attained and maintained under plasticity–induced weight changes. We find that correlations in the input mildly affect the evolution of synaptic weights. Under certain plasticity rules, we find an emergence of correlations between firing rates and synaptic weights. Under these rules, synaptic weights converge to a stable manifold in weight space with their final configuration dependent on the initial state of the network. Lastly, we show that our framework can also describe the dynamics of plastic balanced networks when subsets of neurons receive targeted optogenetic input.


2020 ◽  
Author(s):  
Andrés Fernández ◽  
Elena Quintana ◽  
Patricia Velasco ◽  
Belén de Andrés ◽  
Maria Luisa Gaspar ◽  
...  

Abstract Background: Aging and age related diseases are strong risk factors for the development of neurodegenerative diseases. Neuroinflammation (NIF), as the brain's immune response, plays an important role in aged associated degeneration of central nervous system (CNS). The need of animal models that will allow us to understand and modulate this process is required for the scientific community. Methods: We have analyzed aging-phenotypical and inflammatory changes of brain myeloid cells (bMyC) in a senescent accelerated prone aged (SAMP8) mouse model, and compared with their resistant to senescence control (SAMR1). We have performed morphometric methods to evaluate the architecture of cellular prolongations and analyzed Iba1+ clustered cells with aging. To analyse specific constant brain areas we have performed stereology measurements of Iba1+ cells in the hippocampal formation. We have isolated bMyC from brain parenchyma (BP) and choroid plexus and meningeal membranes (m/Ch), and analyzed their response to systemic LPS- driven inflammation.Results: Aged 10 month old SAMP8 mice presents many of the hallmarks of aging-dependent neuroinflammation when compared with their senescence resistant control (SAMR1); ie, increase of protein aggregates, presence of Iba1+ clusters, but not increase in the number of Iba1+ cells. We have further observed and increased of main inflammatory mediator IL-1β, and augment of border MHCII+Iba1+ cells. Isolated CD45+ bMyC from brain parenchyma (BP) and choroid plexus and meningeal membranes (m/Ch) have been analyzed showing that there is not significant increase of CD45+ from the periphery. Our data support that aged-driven pro-inflammatory cytokine interleukin 1 beta (IL1β) transcription is mainly enhanced in CD45+BP cells. Furthermore, we are showing that LPS-driven systemic inflammation produces inflammatory cytokines mainly in the border bMyC, sensed to a lesser extent by the BP bMyC, and is enhanced in aged SAMP8 compared to control SAMR1.Conclusion: Our data validate the SAMP8 model to study age-associated neuroinflammatory events, but careful controls for age and strain are required. These animals show morphological changes in their bMyC cell repertoires associated to age, corresponding to an increase in the production of main pro inflammatory cytokines such as IL-1β, which predispose the brain to an enhanced inflammatory response after LPS-systemic challenge.


Sign in / Sign up

Export Citation Format

Share Document