chuka_lis (chuka_lis) wrote,

И еще о повреждениях мозга

При ковиде.
Исследования на органоидах мозга ("мозг в пробирке") показали, что если в крови есть вирусы (виремия, обычно это при тяжелом течении), то коронавирус способен проникать в мозг и повреждать сосудистое сплетение желудочков мозга и проходить через гемато-энцефалический барьер.
Авторы в этом исследовании не обнаружили, что коронавирус поражает нейроны или глию.
Coronavirus disease-19 (COVID-19), caused by the SARS-CoV-2 virus, leads to respiratory symptoms that can be fatal. However, neurological symptoms have also been observed in some patients. The cause of these complications is currently unknown. Here, we use human pluripotent stem cell-derived brain organoids to examine SARS-CoV-2 neurotropism
We find expression of viral receptor ACE2 in mature choroid plexus cells expressing abundant lipoproteins, but not in neurons or other cell types. We challenge organoids with SARS-CoV-2 spike pseudovirus and live virus to demonstrate viral tropism for choroid plexus epithelial cells, but little to no infection of neurons or glia.
We find that infected cells are apolipoprotein and ACE2 expressing cells of the choroid plexus epithelial barrier.
Finally, we show that infection with SARS-CoV-2 damages the choroid plexus epithelium, leading to leakage across this important barrier that normally prevents entry of pathogens, immune cells and cytokines into cerebrospinal fluid and the brain.

A likely interpretation of these results is that the neurological symptoms reported in COVID-19 patients are mainly due to an indirect, secondary consequence of viral infection of support cells in the brain, rather than neurons themselves. We show that infection of the ChP epithelium by SARS-CoV-2 leads to disruption of the B-CSF-B, which is in close agreement with recent clinical data demonstrating leakage of blood proteins into CSF in more than 40% of patients 355 tested (Neumann et al., 2020). While this could then allow entry and spread of the virus into the brain, our results suggest that neural cells are minimally susceptible, even when exposed to high quantities of virus. Furthermore, substantial SARS-CoV-2 within the brain and CSF does not seem to be a widely reported finding (Neumann et al., 2020; Schaller et al., 2020). Nonetheless, barrier breakdown could allow abnormal entry of immune cells and cytokines leading to harmful neuroinflammation.

С другой стороны- есть сравнительно свежие и довольно обширные данные бразильцев по клиническим случаям больных с ковидом, включая и тяжелых, и средних ( а так же аутопсий больных, умерших от ковида)- в которых обнаружено, что коронавирус способен поражать астроциты мозга. Неврологические и нейропсихиатрические нарушения были обнаружены  как минимум у трети больных ковидом с умеренным или легким течением ковида, не нуждавшихся в госпитализации и кислородной поддержке, при этом их МРТ сканы показали неравномерные утолщения в отделе передней коры мозга (по сравнениию с контрольной группой- здоровых). ПДФ статьи
Характерно, что нейрологичсекие нарушения оставлась у части тяжелых пациентов и спустя 3 месяца после выписки, когда вирус в мазках  давно уже не выделялся. А исследования  "ин витро" подтвердили, что астрциты могут заражаться вирусом, кронавирус нарушает их метаболизм, работу, а то и убивает вовсе- и- так же- что повреждения астроцитов приводят к повреждениям  или гибели нейронов:

COVID-19 patients may exhibit neuropsychiatric and/or neurological symptoms. We found that anxiety and cognitive impairment are manifested by 28-56% of SARS-CoV-2-infected individuals with mild or no respiratory symptoms and are associated with altered cerebral cortical thickness. Using an independent cohort, we found histopathological signs of brain damage in 19% of individuals who died of COVID-19. All of the affected brain tissues exhibited foci of SARS-CoV-2 infection, particularly in astrocytes. Infection of neural stem cell-derived astrocytes changed energy metabolism, altered key proteins and metabolites used to fuel neurons and for biogenesis of neurotransmitters, and elicited a secretory phenotype that reduces neuronal viability. Our data support the model where SARS-CoV-2 reaches the brain, infects astrocytes and triggers neuropathological changes that contribute to the structural and functional alterations in the brain of COVID-19 patients.

The analysis revealed areas of reduced cortical thickness in theleft lingual gyrus, calcarine sulcus - including the cuneus - and olfactory sulcus - including therectus gyrus .
In contrast, increased thickness was detected in the central sulcus -including the precentral and postcentral gyrus - and superior occipital gyrus, which canbe associated with vasogenic edemas ​7​. A subgroup of these individuals (n = 61) were subjectedto neuropsychological evaluation for anxiety (Beck Anxiety Inventory, BAI), depression (BeckDepression Inventory, BDI), logical memory (Wechsler Memory Scale), cognitive functions(TRAIL Making Test) and fatigue (Chalder Fatigue Questionnaire, CFQ). These tests wereperformed between 21 and 120 days after diagnosis (median of 59 days). Symptoms of anxietywere identified in approximately 28% of the subjects, and 20% of individuals presentedsymptoms of depression . Abnormal performances were observed innearly 28% of participants on logical memory and approximately 34% and 56% on TRAIL Aand B, respectively. We also correlated thechanges in cortex thickness with the neuropsychological evaluation. We identified a negativecorrelation between BAI and cortical thickness of orbitofrontal regions (adjusted for CFQ)  and a positive correlation between TRAIL B and corticalthickness of the right gyrus rectus  We also found partialcorrelations between logical memory (immediate recall, adjusted for BAI, BDI and CFQ) and cortical thickness of regions associated with language. ​These resultssuggest that a thinner cortex in these areas is associated with poor performance on this verbalmemory task. Ov​erall, our findings evidence major alterations in brain cortex structureassociated with neuropsychiatric symptoms as a consequence of COVID-19.Brain alterations in COVID-19 patients could be a consequence of inflammatory or hemodynamic changes secondary to peripheral infection or could be caused by the ability ofSARS-CoV-2 to invade the central nervous system (CNS) and compromise cell viability andbrain function.
We performed a minimally invasive autopsy via endonasal trans-ethmoidal access ofbrain samples from 26 individuals who died of COVID-19 and analyzed histopathologicalfeatures. We found alterations consistent with necrosis and inflammation in 19% of the braintissues from these individuos (5/20) . Notably, SARS-CoV-2genetic material and spike protein was detected in all of these five samples .SARS-CoV-2 spike protein was found in about one third of the cells in one of the slices of braintissue analyzed the majority of these cells being astrocytes.  We also found thevirus in neurons, but not in microglia . Thepresence of SARS-CoV-2 spike protein correlated with the presence of double-stranded RNA(dsRNA) in the infected cells, indicating replicative virus in the brain tissuе.
We have also conducted liquid chromatography-mass spectrometry (LC/MS)-basedshotgun proteomics with a different set of samples, consisting of 12 ​postmortem​ brain samplesfrom COVID-19 patients vs. 8 SARS-CoV-2-negative controls. We identified 119 differentiallyexpressed proteins with the most highly enriched pathways being associated with neurodegenerative diseases and carbon metabolism. Moreover, astrocyte proteins wereenriched among the differentially expressed proteins, consistent with the higher frequency ofinfected astrocytes. In order to investigate the consequences of SARS-CoV-2 infection on astrocytes, wegenerated human neural stem cell-derived astrocytes, exposed them to the virus for 1h, andanalyzed cell response after 24h. We confirmed that SARS-CoV-2 is able to infect humanastrocytes Notably, we also found the presence of dsRNA in SARS-CoV-2-infectedastrocytes i​n vitro​, but not in mock control cells. Altogether these results indicate thatastrocytes are permissive cells for SARS-CoV-2 infection and represent a site for virusreplication in the central nervous system.
 Кроме того, врачами уже задокументированы случаи, что ковид может приводить к потере слуха или серьезному ухудшению зрениялаукоме).
Tags: здоровье, коронавирус, мозг, статьи

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