scholarly journals Therapeutic Applications of Resveratrol in Hepatic Encephalopathy through Its Regulation of the Microbiota, Brain Edema, and Inflammation

2021 ◽  
Vol 10 (17) ◽  
pp. 3819
Author(s):  
Young-Kook Kim ◽  
Juhyun Song
Keyword(s):  
Hepatic Encephalopathy ◽  
Brain Edema ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Current Evidence ◽  
Astrocyte Swelling ◽  
Chronic Neuroinflammation ◽  
Gut Barrier Function ◽  
Portosystemic Shunting ◽  
Neuropsychiatric Manifestations

Hepatic encephalopathy is a common complication in patients with liver cirrhosis and portosystemic shunting. Patients with hepatic encephalopathy present a variety of clinical features, including neuropsychiatric manifestations, cognitive dysfunction, impaired gut barrier function, hyperammonemia, and chronic neuroinflammation. These pathogeneses have been linked to various factors, including ammonia-induced oxidative stress, neuronal cell death, alterations in the gut microbiome, astrocyte swelling, and blood-brain barrier disruptions. Many researchers have focused on identifying novel therapeutics and prebiotics in the hope of improving the treatment of these conditions. Resveratrol is a natural polyphenic compound and is known to exert several pharmacological effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Recent studies suggest that resveratrol contributes to improving the neuropathogenic effects of liver failure. Here, we review the current evidence describing resveratrol’s effects in neuropathogenesis and its impact on the gut-liver axis relating to hepatic encephalopathy. We highlight the hypothesis that resveratrol exerts diverse effects in hepatic encephalopathy and suggest that these effects are likely mediated by changes to the gut microbiota, brain edema, and neuroinflammation.

scholarly journals The Potential Neuroprotective Role of Free and Encapsulated Quercetin Mediated by miRNA against Neurological Diseases

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1318
Author(s):  
Tarek Benameur ◽  
Raffaella Soleti ◽  
Chiara Porro
Keyword(s):  
Inflammatory Responses ◽  
Pathological Condition ◽  
Neurological Diseases ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
In Vivo Studies ◽  
Innovative Drug ◽  
Chronic Neuroinflammation

Chronic neuroinflammation is a pathological condition of numerous central nervous system (CNS) diseases such as Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis and many others. Neuroinflammation is characterized by the microglia activation and concomitant production of pro-inflammatory cytokines leading to an increasing neuronal cell death. The decreased neuroinflammation could be obtained by using natural compounds, including flavonoids known to modulate the inflammatory responses. Among flavonoids, quercetin possess multiple pharmacological applications including anti-inflammatory, antitumoral, antiapoptotic and anti-thrombotic activities, widely demonstrated in both in vitro and in vivo studies. In this review, we describe the recent findings about the neuroprotective action of quercetin by acting with different mechanisms on the microglial cells of CNS. The ability of quercetin to influence microRNA expression represents an interesting skill in the regulation of inflammation, differentiation, proliferation, apoptosis and immune responses. Moreover, in order to enhance quercetin bioavailability and capacity to target the brain, we discuss an innovative drug delivery system. In summary, this review highlighted an important application of quercetin in the modulation of neuroinflammation and prevention of neurological disorders.

scholarly journals SARS-CoV-2 Neurotropism and Single Cell Responses in Brain Organoids Containing Innately Developing Microglia

2021 ◽  
Author(s):  
Samudyata ◽  
Ana Osorio Oliveira ◽  
Susmita Malwade ◽  
Nuno Rufino de Sousa ◽  
Sravan K Goparaju ◽  
...  
Keyword(s):  
Single Cell ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Cellular Responses ◽  
Cellular Respiration ◽  
Neuropsychiatric Manifestations ◽  
Altered Blood ◽  
Cell Transcriptome

Neuropsychiatric manifestations are common in both acute and post-acute phase of SARS-CoV-2 infection, but the mechanism of these effects is unknown. Here, we derive human brain organoids with innately developing microglia to investigate the cellular responses to SARS-CoV-2 infection on a single cell level. We find evidence of limited tropism to SARS-CoV-2 for all major cell types and observe extensive neuronal cell death that also include non-infected cells. Single cell transcriptome profiling reveals distinct responses in microglia and astrocytes that share features with cellular states observed in neurodegenerative diseases, includes upregulation of genes with relevance for synaptic stripping, and suggests altered blood brain barrier integrity. Across all cell types, we observe a global translational shut-down as well as altered carbohydrate metabolism and cellular respiration. Together, our findings provide insights into cellular responses of the resident brain immune cells to SARS-CoV-2 and pinpoint mechanisms that may be of relevance for the neuropathological changes observed in COVID-19 patients.

scholarly journals Microglial depletion with CSF1R inhibitor during chronic phase of experimental traumatic brain injury reduces neurodegeneration and neurological deficits

2019 ◽  
Author(s):  
Rebecca J. Henry ◽  
Rodney M. Ritzel ◽  
James P. Barrett ◽  
Sarah J. Doran ◽  
Yun Jiao ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Chronic Phase ◽  
Neurological Dysfunction ◽  
Neurological Deficits ◽  
Cortical Lesion ◽  
Translational Study ◽  
Chronic Neuroinflammation

AbstractChronic neuroinflammation with sustained microglial activation occurs following moderate-to-severe traumatic brain injury (TBI) and is believed to contribute to subsequent neurodegeneration and neurological deficits. Microglia, the primary innate immune cells in brain, are dependent on colony stimulating factor 1 receptor (CSF1R) signaling for their survival. In this translational study, we examined the effects of delayed depletion and subsequent repopulation of microglia on chronic neurodegeneration and functional recovery up to three months posttrauma. A CSF1R inhibitor, PLX5622, was administered to injured adult male C57Bl/6 mice at one month after controlled cortical impact to remove chronically activated microglia, and the inihibitor was withdrawn 1 week later to allow microglial repopulation. Following TBI, the repopulated microglia displayed a ramified morphology, similar to that of sham control uninjured animals, whereas microglia in untreated injured animals showed the typical chronic posttraumatic hypertrophic morphology. PLX5622 treatment limited TBI-associated neuropathological changes at 3 months posttrauma; these included a smaller cortical lesion, reduced neuronal cell death in the injured cortex and ipsilateral hippocampus, and decreased NOX2-dependent reactive microgliosis. Furthermore, delayed depletion of microglia led to widespread changes in the cortical transcriptome, including alterations in gene pathways involved in neuroinflammation, oxidative stress, and neuroplasticity. PLX5622 treated animals showed significantly improved neurological recovery using a variety of complementary neurobehavioral evaluations. These included beam walk and rotorod tests for sensori-motor function, as well as Y-maze, novel object recognition, and Morris water maze tests to evaluate cognitive function. Together, our findings show that chronic phase removal of neurotoxic microglia using CSF1R inhibitors after experimental TBI can markedly reduce chronic neuroinflammation and neurodegeneration, as well as related long-term motor and cognitive deficits. Thus, CSF1R inhibition may provide a clinically feasible approach to limit posttraumatic neurodegeneration and neurological dysfunction following head injury.

scholarly journals SARS-CoV-2 Neurotropism and Single Cell Responses in Brain Organoids Containing Innately Developing Microglia

2021 ◽  
Author(s):  
Samudyata Samudyata ◽  
Ana Oliveira ◽  
Susmita Malwade ◽  
Nuno Rufino de Sousa ◽  
Sravan Goparaju ◽  
...  
Keyword(s):  
Single Cell ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Cellular Responses ◽  
Cellular Respiration ◽  
Neuropsychiatric Manifestations ◽  
Altered Blood ◽  
Cell Transcriptome

Abstract Neuropsychiatric manifestations are common in both acute and post-acute phase of SARS-CoV-2 infection, but the mechanism of these effects is unknown. Here, we derive human brain organoids with innately developing microglia to investigate the cellular responses to SARS-CoV-2 infection on a single cell level. We find evidence of limited tropism to SARS-CoV-2 and observe extensive neuronal cell death that also include non-infected cells. Single cell transcriptome profiling reveals distinct responses in microglia and astrocytes that share features with cellular states observed in neurodegenerative diseases, includes upregulation of genes with relevance for synaptic stripping, and suggests altered blood brain barrier integrity. Across all cell types, we observe a global translational shut-down as well as altered carbohydrate metabolism and cellular respiration. Together, our findings provide insights into cellular responses of the resident brain immune cells to SARS-CoV-2 and pinpoint mechanisms that may be of relevance for the neuropathological changes observed in COVID-19 patients.

scholarly journals Traumatic Brain Injury and NADPH Oxidase: A Deep Relationship

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Cristina Angeloni ◽  
Cecilia Prata ◽  
Francesco Vieceli Dalla Sega ◽  
Roberto Piperno ◽  
Silvana Hrelia
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurological Diseases ◽  
Critical Role ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Direct Result ◽  
Current Evidence ◽  
Causes Of Mortality ◽  
Deep Relationship

Traumatic brain injury (TBI) represents one of the major causes of mortality and disability in the world. TBI is characterized by primary damage resulting from the mechanical forces applied to the head as a direct result of the trauma and by the subsequent secondary injury due to a complex cascade of biochemical events that eventually lead to neuronal cell death. Oxidative stress plays a pivotal role in the genesis of the delayed harmful effects contributing to permanent damage. NADPH oxidases (Nox), ubiquitary membrane multisubunit enzymes whose unique function is the production of reactive oxygen species (ROS), have been shown to be a major source of ROS in the brain and to be involved in several neurological diseases. Emerging evidence demonstrates that Nox is upregulated after TBI, suggesting Nox critical role in the onset and development of this pathology. In this review, we summarize the current evidence about the role of Nox enzymes in the pathophysiology of TBI.

Sign in / Sign up

Export Citation Format

Share Document