Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms

Brain Behavior and Immunity, Journal Year: 2020, Volume and Issue: 87, P. 34 - 39

Published: April 13, 2020

Language: Английский

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Pneumonia

Nature Reviews Disease Primers, Journal Year: 2021, Volume and Issue: 7(1)

Published: April 8, 2021

Language: Английский

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Cognitive impairment and altered cerebral glucose metabolism in the subacute stage of COVID-19

Brain, Journal Year: 2021, Volume and Issue: 144(4), P. 1263 - 1276

Published: Jan. 18, 2021

During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, neurological symptoms increasingly moved into focus of interest. In this prospective cohort study, we assessed and cognitive in hospitalized disease-19 (COVID-19) patients aimed to determine their neuronal correlates. Patients with reverse transcription-PCR-confirmed COVID-19 infection who required inpatient treatment primarily because non-neurological complications were screened between 20 April 2020 12 May 2020. (age > 18 years) included our when presenting at least one new symptom (defined as impaired gustation and/or olfaction, performance < 26 points on a Montreal Cognitive Assessment pathological findings clinical examination). ≥2 eligible for further diagnostics using comprehensive neuropsychological tests, cerebral MRI 18fluorodeoxyglucose (FDG) PET soon infectivity was no longer present. Exclusion criteria were: premorbid diagnosis impairment, neurodegenerative diseases or intensive care unit treatment. Of 41 inpatients screened, 29 (65.2 ± 14.4 years; 38% female) subacute stage disease register. Most frequently, olfaction disturbed 29/29 25/29 patients, respectively. 18/26 (mean score 21.8/30) emphasis frontoparietal functions. This confirmed by detailed testing 15 patients. 18FDG revealed results 10/15 predominant hypometabolism. pattern comparison control sample voxel-wise principal components analysis, which showed high correlation (R2 = 0.62) performance. Post-mortem examination patient white matter microglia activation but signs neuroinflammation. Neocortical dysfunction accompanied decline detected relevant fraction initially requiring is major rehabilitative socioeconomic relevance.

Language: Английский

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Psychiatric face of COVID-19

Translational Psychiatry, Journal Year: 2020, Volume and Issue: 10(1)

Published: July 30, 2020

Abstract The Coronavirus Disease 2019 (COVID-19) represents a severe multiorgan pathology which, besides cardio-respiratory manifestations, affects the function of central nervous system (CNS). acute respiratory syndrome coronavirus 2 (SARS-CoV-2), similarly to other coronaviruses demonstrate neurotropism; viral infection brain stem may complicate course disease through damaging control. systemic inflammation as well neuroinflammatory changes are associated with massive increase pro-inflammatory molecules, neuroglial reactivity, altered neurochemical landscape and pathological remodelling neuronal networks. These organic changes, emerging in concert environmental stress caused by experiences intensive therapy wards, pandemic fears social restrictions, promote neuropsychiatric pathologies including major depressive disorder, bipolar disorder (BD), various psychoses, obsessive-compulsive post-traumatic disorder. sequelae COVID-19 represent serious clinical challenge that has be considered for future complex therapies.

Language: Английский

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Sepsis-associated encephalopathy and septic encephalitis: an update

Expert Review of Anti-infective Therapy, Journal Year: 2020, Volume and Issue: 19(2), P. 215 - 231

Published: Aug. 19, 2020

Introduction Sepsis-associated encephalopathy (SAE) and septic encephalitis (SE) are associated with increased mortality, long-term cognitive impairment, focal neurological deficits.Areas covered The PUBMED database was searched 2016–2020. clinical manifestation of SAE is delirium, SE additionally characterized by symptoms. caused inflammation endothelial/microglial activation, increase permeability the blood-brain-barrier, hypoxia, imbalance neurotransmitters, glial axonal, neuronal loss. Septic-embolic (SEE) septic-metastatic (SME) ischemia small abscesses (SME). continuum between SAE, SME, SEE documented imaging techniques autopsies. backbone treatment rapid optimum antibiotic therapy. Experimental approaches focus on modulation inflammation, stabilization blood-brain barrier, restoration membrane/mitochondrial function.Expert opinion most promising diagnostic new techniques. important measure to fight delirium remains establishment daily structure adequate sensory stimuli. Dexmedetomidine melatonin appear reduce frequency their efficacy in be established. Drugs already licensed for other indications or available as food supplements which may effective statins, L-DOPA/benserazide, β-hydroxybutyrate, palmitoylethanolamide, tetracyclines bactericidal non-lytic antibiotics.

Language: Английский

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Sepsis-associated brain injury: underlying mechanisms and potential therapeutic strategies for acute and long-term cognitive impairments

Journal of Neuroinflammation, Journal Year: 2022, Volume and Issue: 19(1)

Published: April 29, 2022

Abstract Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. causes cerebral in the short and long term induces disruption of blood–brain barrier (BBB), neuroinflammation, hypoperfusion, accumulation amyloid β (Aβ) tau protein brain. White matter changes brain atrophy can be detected using imaging, but unfortunately, there no specific treatment that directly addresses underlying mechanisms cognitive impairments sepsis. Here, we review sepsis-associated injury, with focus on BBB Aβ We also describe neurological manifestations imaging findings finally, propose potential therapeutic strategies for acute long-term associated In phase sepsis, suggest antibiotics (such as rifampicin), targeting proinflammatory cytokines, preventing ischemic injuries hypoperfusion. late dysfunction, phosphorylation, glycogen synthase kinase-3 beta (GSK3β), receptor advanced glycation end products (RAGE). These proposed are meant bring new mechanism-based directions future basic clinical research aimed at or ameliorating patients

Language: Английский

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Microglia mediate neurocognitive deficits by eliminating C1q-tagged synapses in sepsis-associated encephalopathy

Science Advances, Journal Year: 2023, Volume and Issue: 9(21)

Published: May 26, 2023

Sepsis-associated encephalopathy (SAE) is a severe and frequent complication of sepsis causing delirium, coma, long-term cognitive dysfunction. We identified microglia C1q complement activation in hippocampal autopsy tissue patients with increased C1q-mediated synaptic pruning murine polymicrobial model. Unbiased transcriptomics isolated derived from septic mice revealed an involvement the innate immune system, activation, up-regulation lysosomal pathways during SAE parallel to neuronal damage. Microglial engulfment C1q-tagged synapses could be prevented by stereotactic intrahippocampal injection specific C1q-blocking antibody. Pharmacologically targeting PLX5622, CSF1-R inhibitor, reduced levels number synapses, protected damage synapse loss, improved neurocognitive outcome. Thus, we complement-dependent as crucial pathomechanism for development defects SAE.

Language: Английский

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β-Nicotinamide mononucleotide activates NAD+/SIRT1 pathway and attenuates inflammatory and oxidative responses in the hippocampus regions of septic mice

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102745 - 102745

Published: May 13, 2023

Sepsis-associated encephalopathy (SAE) is one of the common serious complications in sepsis, and pathogenesis SAE remains unclear. Sirtuin 1 (SIRT1) has been reported to be downregulated hippocampus SIRT1 agonists can attenuated cognitive dysfunction septic mice. Nicotinamide adenine dinucleotide (NAD+) a key substrate maintain deacetylation activity SIRT1. As an intermediate NAD+, β-Nicotinamide Mononucleotide (NMN) promising treating neurodegenerative diseases cerebral ischemic injury. Thus we sought investigate potential role NMN treatment. The model was established by cecal ligation puncture (CLP) vivo, neuroinflammation with LPS-treated BV-2 cells vitro. Memory impairment assessed Morris water maze fear conditioning tests. result, levels PGC-1α were significantly reduced mice, while acetylation total lysine, phosphorylation P38 P65 enhanced. All these changes induced sepsis inverted NMN. Treating resulted improved behavior performance tests maze. Apoptosis, inflammatory oxidative responses mice after administration. These protective effect against memory dysfunction, injuries reversed inhibitor, EX-527. Similarly, LPS-induced activation NMN, EX-527 or knockdown could reverse such In conclusion, sepsis-induced region NAD+/SIRT1 pathway might involved mechanisms effect.

Language: Английский

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Short-chain fatty acids-producing probiotics: A novel source of psychobiotics

Critical Reviews in Food Science and Nutrition, Journal Year: 2021, Volume and Issue: 62(28), P. 7929 - 7959

Published: May 6, 2021

Psychobiotics-live microorganisms with potential mental health benefits, which can modulate the microbiota-gut-brain-axis via immune, humoral, neural, and metabolic pathways-are emerging as novel therapeutic options for effective treatment of psychiatric disorders Recently, microbiome studies have identified numerous putative psychobiotic strains, short-chain fatty acids (SCFAs) producing bacteria attracted special attention from neurobiologists. Recent highlighted that SCFAs-producing such Lactobacillus, Bifidobacterium Clostridium a very specific function in various disorders, suggesting these be psychobiotics. SCFAs, mediators microbiota-gut-brain axis, might neurological processes. While roles mechanisms microbiota-targeted interventions on neuropsychiatric disease are largely unknown. This Review summarizes existing knowledge neuroprotective effects modulating axis illustrate their possible by may act will shed light promising source

Language: Английский

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Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis‐associated encephalopathy

CNS Neuroscience & Therapeutics, Journal Year: 2021, Volume and Issue: 28(2), P. 247 - 258

Published: Nov. 27, 2021

Fisetin, the effective ingredient of traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role sepsis-associated encephalopathy (SAE) remains unclarified.Cecal ligation and puncture (CLP) operation was performed establish a rat model SAE. Rats were grouped according surgery fisetin administration. Cognitive impairment assessed by Morris water maze test. Disruption blood-brain barrier (BBB) integrity detected Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, pro-inflammatory cytokines levels measured through western blot double immunofluorescence labeling. A transmission electron microscope applied for observation mitochondrial autophagosomes.Rats CLP group presented increased expression IL-1R1, pNF-κB, TNF-α, iNOS microglial cells, indicating severe inflammation central nervous system (CNS). Nevertheless, there no increase BBB permeability. Meanwhile, activated cerebral microvascular endothelial cells (CMECs), with an elevation caspase-1 IL-1β secretion into CNS. In addition, we found significantly improved cognitive dysfunction rats Neuroprotective effects might associated inhibition neuroinflammation, represented decreased microglia. Furthermore, induced scavenged ROS, blocked activation CMECs, as evidenced reduced release CNS.Collectively, fisetin-blocked via promoting mitophagy CMECs may suppress CNS, reduce contribute amelioration impairment.

Language: Английский

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