scholarly journals Neuro-oxidative-nitrosative stress in sepsis

2011 ◽  
Vol 31 (7) ◽  
pp. 1532-1544 ◽  
Author(s):  
Ronan MG Berg ◽  
Kirsten Møller ◽  
Damian M Bailey

Neuro-oxidative-nitrosative stress may prove the molecular basis underlying brain dysfunction in sepsis. In the current review, we describe how sepsisinduced reactive oxygen and nitrogen species (ROS/RNS) trigger lipid peroxidation chain reactions throughout the cerebrovasculature and surrounding brain parenchyma, due to failure of the local antioxidant systems. ROS/RNS cause structural membrane damage, induce inflammation, and scavenge nitric oxide (NO) to yield peroxynitrite (ONOO−). This activates the inducible NO synthase, which further compounds ONOO− formation. ROS/RNS cause mitochondrial dysfunction by inhibiting the mitochondrial electron transport chain and uncoupling oxidative phosphorylation, which ultimately leads to neuronal bioenergetic failure. Furthermore, in certain ‘at risk’ areas of the brain, free radicals may induce neuronal apoptosis. In the present review, we define a role for ROS/RNS-mediated neuronal bioenergetic failure and apoptosis as a primary mechanism underlying sepsis-associated encephalopathy and, in sepsis survivors, permanent cognitive deficits.

2019 ◽  
Vol 20 (10) ◽  
pp. 2600 ◽  
Author(s):  
Masaki Ueno ◽  
Yoichi Chiba ◽  
Ryuta Murakami ◽  
Koichi Matsumoto ◽  
Ryuji Fujihara ◽  
...  

The entry of blood-borne macromolecular substances into the brain parenchyma from cerebral vessels is blocked by the blood–brain barrier (BBB) function. Accordingly, increased permeability of the vessels induced by insult noted in patients suffering from vascular dementia likely contributes to the cognitive impairment. On the other hand, blood-borne substances can enter extracellular spaces of the brain via endothelial cells at specific sites without the BBB, and can move to brain parenchyma, such as the hippocampus and periventricular areas, adjacent to specific sites, indicating the contribution of increased permeability of vessels in the specific sites to brain function. It is necessary to consider influx and efflux of interstitial fluid (ISF) and cerebrospinal fluid (CSF) in considering effects of brain transfer of intravascular substances on brain function. Two pathways of ISF and CSF are recently being established. One is the intramural peri-arterial drainage (IPAD) pathway of ISF. The other is the glymphatic system of CSF. Dysfunction of the two pathways could also contribute to brain dysfunction. We review the effects of several kinds of insult on vascular permeability and the failure of fluid clearance on the brain function.


Although Covid-19 disease is primarily considered an infection of the respiratory tract, it is currently known that damage and adverse reactions in the course of and after this disease affect several other bodily systems, however these issues are not yet fully understood, especially in tangent its neurological manifestations.3,4 In this sense, this report aims to add the list of many cases that are being reported/described in the literature which warn about the direct effects of the virus on the nervous system, to a disease for -infectious or post-infectious immune-mediated to COVID-19, such as acute disseminated encephalomyelitis, muscular diseases of the peripheral nervous system (Guillain-Barré syndrome), cerebrovascular and vascular diseases (CVA), and acute inflammatory processes such as that of the brain parenchyma in this case of Viral Encephalitis. Encephalitis is a diffuse or focal inflammatory process of the brain parenchyma associated with brain dysfunction, which can be divided into two main categories: alluding to systemic infections or vaccination and alluding to the entry of the pathogen into the CNS. Thus, based on the premise that several neurological manifestations are related to SARS-CoV-2 infection, a better understanding of the immune response to this infection can help not only for prevention but also can provide a valuable contribution to knowledge of the health-disease process, next human approaches, therapeutic and drug interventions


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 907
Author(s):  
Mario Díaz ◽  
Fátima Mesa-Herrera ◽  
Raquel Marín

DHA (docosahexaenoic acid) is perhaps the most pleiotropic molecule in nerve cell biology. This long-chain highly unsaturated fatty acid has evolved to accomplish essential functions ranging from structural components allowing fast events in nerve cell membrane physiology to regulation of neurogenesis and synaptic function. Strikingly, the plethora of DHA effects has to take place within the hostile pro-oxidant environment of the brain parenchyma, which might suggest a molecular suicide. In order to circumvent this paradox, different molecular strategies have evolved during the evolution of brain cells to preserve DHA and to minimize the deleterious effects of its oxidation. In this context, DHA has emerged as a member of the “indirect antioxidants” family, the redox effects of which are not due to direct redox interactions with reactive species, but to modulation of gene expression within thioredoxin and glutathione antioxidant systems and related pathways. Weakening or deregulation of these self-protecting defenses orchestrated by DHA is associated with normal aging but also, more worryingly, with the development of neurodegenerative diseases. In the present review, we elaborate on the essential functions of DHA in the brain, including its role as indirect antioxidant, the selenium connection for proper antioxidant function and their changes during normal aging and in Alzheimer’s disease.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Alice Buonfiglioli ◽  
Dolores Hambardzumyan

AbstractGlioblastoma (GBM) is the most aggressive and deadliest of the primary brain tumors, characterized by malignant growth, invasion into the brain parenchyma, and resistance to therapy. GBM is a heterogeneous disease characterized by high degrees of both inter- and intra-tumor heterogeneity. Another layer of complexity arises from the unique brain microenvironment in which GBM develops and grows. The GBM microenvironment consists of neoplastic and non-neoplastic cells. The most abundant non-neoplastic cells are those of the innate immune system, called tumor-associated macrophages (TAMs). TAMs constitute up to 40% of the tumor mass and consist of both brain-resident microglia and bone marrow-derived myeloid cells from the periphery. Although genetically stable, TAMs can change their expression profiles based upon the signals that they receive from tumor cells; therefore, heterogeneity in GBM creates heterogeneity in TAMs. By interacting with tumor cells and with the other non-neoplastic cells in the tumor microenvironment, TAMs promote tumor progression. Here, we review the origin, heterogeneity, and functional roles of TAMs. In addition, we discuss the prospects of therapeutically targeting TAMs alone or in combination with standard or newly-emerging GBM targeting therapies.


Author(s):  
F. Riva ◽  
T. Fracasso ◽  
A. Guerra ◽  
P. Genet

AbstractIn shooting crimes, ballistics tests are often recommended in order to reproduce the wound characteristics of the involved persons. For this purpose, several “simulants” can be used. However, despite the efforts in the research of “surrogates” in the field of forensic ballistic, the development of synthetic models needs still to be improved through a validation process based on specific real caseworks. This study has been triggered by the findings observed during the autopsy performed on two victims killed in the same shooting incident, with similar wounding characteristics; namely two retained head shots with ricochet against the interior wall of the skull; both projectiles have been recovered during the autopsies after migration in the brain parenchyma. The thickness of the different tissues and structures along the bullets trajectories as well as the incident angles between the bullets paths and the skull walls have been measured and reproduced during the assemblage of the synthetic head models. Two different types of models (“open shape” and “spherical”) have been assembled using leather, polyurethane and gelatine to simulate respectively skin, bone and soft tissues. Six shots have been performed in total. The results of the models have been compared to the findings of post-mortem computed tomography (PMCT) and the autopsy findings.Out of the six shots, two perforated the models and four were retained. When the projectile was retained, the use of both models allowed reproducing the wounds characteristics observed on both victims in terms of penetration and ricochet behaviour. However, the projectiles recovered from the models showed less deformation than the bullets collected during the autopsies. The “open shape” model allowed a better controlling on the shooting parameters than the “spherical” model. Finally, the difference in bullet deformation could be caused by the choice of the bone simulant, which might under-represent either the strength or the density of the human bone. In our opinion, it would be worth to develop a new, more representative material for ballistic which simulates the human bone.


2021 ◽  
pp. 1118-1123
Author(s):  
Kengo Setta ◽  
Takaaki Beppu ◽  
Yuichi Sato ◽  
Hiroaki Saura ◽  
Junichi Nomura ◽  
...  

Malignant lymphoma of the head rarely arises outside of the brain parenchyma as primary cranial vault lymphoma (PCVL). A case of PCVL that invaded from subcutaneous tissue into the brain, passing through the skull, and occurred after mild head trauma is reported along with a review of the literature. The patient was a 75-year-old man with decreased activity. One month before his visit to our hospital, he bruised the left frontal area of his head. Magnetic resonance imaging showed homogeneously enhanced tumors with contrast media in the subcutaneous tissue corresponding to the head impact area and the cerebral parenchyma, but no obvious abnormal findings in the skull. A biopsy with craniotomy was performed under general anesthesia. The pathological diagnosis was diffuse large B-cell lymphoma. On histological examination, tumor cells grew aggressively under the skin. Tumor cells invaded along the emissary vein into the external table without remarkable bone destruction and extended across the skull through the Haversian canals in the diploe. Tumor cells were found only at the perivascular areas in the dura mater and extended into the brain parenchyma. Considering the history of head trauma and the neuroimaging and histological findings, the PCVL in the present case arose primarily under the skin, passed though the skull and dura mater, and invaded along vessels and reached the brain.


Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 957
Author(s):  
Brad T. Casali ◽  
Erin G. Reed-Geaghan

Microglia are the resident immune cells of the brain, deriving from yolk sac progenitors that populate the brain parenchyma during development. During development and homeostasis, microglia play critical roles in synaptogenesis and synaptic plasticity, in addition to their primary role as immune sentinels. In aging and neurodegenerative diseases generally, and Alzheimer’s disease (AD) specifically, microglial function is altered in ways that significantly diverge from their homeostatic state, inducing a more detrimental inflammatory environment. In this review, we discuss the receptors, signaling, regulation and gene expression patterns of microglia that mediate their phenotype and function contributing to the inflammatory milieu of the AD brain, as well as strategies that target microglia to ameliorate the onset, progression and symptoms of AD.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii41-ii41
Author(s):  
Junjie Zhen ◽  
Lei Wen ◽  
Shaoqun Li ◽  
Mingyao Lai ◽  
Changguo Shan ◽  
...  

Abstract BACKGROUND According to EANO-ESMO clinical practice guidelines, the MRI findings of LM are divided into 4 types, namely linear enhancement (type A), nodular enhancement (type B), linear combined with nodular enhancement (type C), and sign of hydrocephalus (type D). METHODS The MRI features of brain and spinal cord in patients diagnosed with NSCLC-LM in Guangdong Sanjiu Brain Hospital from 2010 until 2019 were investigated, and then were classified into 4 types. The imaging features were analyzed. RESULTS A total of 80 patients were enrolled in the study. The median age of the patients was 53.5 years old, and the median time from the initial diagnosis to the confirmed diagnosis of LM was 11.6 months. The results of enhanced MRI examination of the brain in 79 cases showed that the number of cases with enhancements of type A, B, C and D were 50 (63.3%), 0, 26 (32.9%) and 3 (3.8%), respectively, and that LM with metastases to the brain parenchyma was found in 42 cases (53.2%). The results of enhanced MRI examination of spinal cord in 59 cases showed that there were only enhancements of type A and C in 40 cases (67.8%) and 3 cases (5.0%), and no enhancement sign in the other 16 cases (27.2%). CONCLUSION MRI examination of brain and spinal cord will improve the detection rate of LM. The MRI features of NSCLC-LM in real world are mainly characterized by the linear enhancements of brain and spinal cord, followed by linear combined with nodular enhancement. The enhancements of type B and type D are rare in clinic. Almost half of the patients have LM and metastases to the brain parenchyma. Therefore, the differentiation of tumor metastases is needed to be paid attention to for the early diagnosis and the formulation of reasonable treatment plans.


1996 ◽  
Vol 6 (5) ◽  
pp. 363-371 ◽  
Author(s):  
T Fujimaki ◽  
J E Price ◽  
D Fan ◽  
C D Bucana ◽  
K Itoh ◽  
...  

2016 ◽  
Vol 7 ◽  
pp. 645-654 ◽  
Author(s):  
Bin Song ◽  
Yanli Zhang ◽  
Jia Liu ◽  
Xiaoli Feng ◽  
Ting Zhou ◽  
...  

Titanium dioxide nanoparticles (TiO2 NPs) possess unique characteristics and are widely used in many fields. Numerous in vivo studies, exposing experimental animals to these NPs through systematic administration, have suggested that TiO2 NPs can accumulate in the brain and induce brain dysfunction. Nevertheless, the exact mechanisms underlying the neurotoxicity of TiO2 NPs remain unclear. However, we have concluded from previous studies that these mechanisms mainly consist of oxidative stress (OS), apoptosis, inflammatory response, genotoxicity, and direct impairment of cell components. Meanwhile, other factors such as disturbed distributions of trace elements, disrupted signaling pathways, dysregulated neurotransmitters and synaptic plasticity have also been shown to contribute to neurotoxicity of TiO2 NPs. Recently, studies on autophagy and DNA methylation have shed some light on possible mechanisms of nanotoxicity. Therefore, we offer a new perspective that autophagy and DNA methylation could contribute to neurotoxicity of TiO2 NPs. Undoubtedly, more studies are needed to test this idea in the future. In short, to fully understand the health threats posed by TiO2 NPs and to improve the bio-safety of TiO2 NPs-based products, the neurotoxicity of TiO2 NPs must be investigated comprehensively through studying every possible molecular mechanism.


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