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Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

ABSTRACT: Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management.

SUBMITTER: Dong H

PROVIDER: S-EPMC10899346 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

Dong Hao H Wen Xin X Zhang Bai-Wen BW Wu Zhe Z Zou Wei W

Frontiers in molecular neuroscience 20240214

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the ...[more]

PMID: 38419793

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Project description:BackgroundAlthough a great deal of research has explored the possibility of a systemic inflammatory response and dysbiosis of the gut microbiota after an intracerebral hemorrhage (ICH), the relationships between gut microbiota and blood inflammatory indicators as well as their role in the hematoma expansion following an early-stage mild-to-moderate ICH (emICH) remain unknown. This study analyzes these changes and associations in order to predict and prevent hematoma expansion after emICH.MethodsThe study included 100 participants, with 70 individuals diagnosed with emICH (30 with hematoma expansion and 40 without hematoma expansion, referred to as the HE and NE groups) and 30 healthy controls matched in terms of age and gender (HC). We used 16S rRNA gene sequencing to explore the gut microbial structure and its underlying associations with blood inflammatory parameters in the HE group.ResultsOur findings showed a significant decrease in the diversity and even distribution of microorganisms in the HE group when compared to the HC and NE groups. The composition of the gut microbiota experienced notable alterations in the emICH group, especially in HE. These changes included a rise in the number of gram-negative pro-inflammatory bacteria and a decline in the level of probiotics. Furthermore, we observed strong positive connections between bacteria enriched in the HE group and levels of systemic inflammation. Several microbial biomarkers (e.g. Escherichia_Shigella, Enterobacter, and Porphyromonas) were revealed in disparateiating HE from HC and NE. Analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) exposed disturbances in essential physiological pathways, especially those related to inflammation (such as the Toll-like receptor signaling pathway), in the HE group.ConclusionsOur exploration indicated that individuals with emICH, especially those with HE, demonstrate notably different host-microbe interactions when compared to healthy individuals. We deduced that emICH could rapidly trigger the dysbiosis of intestinal flora, and the disturbed microbiota could, in turn, exacerbate inflammatory response and increase the risk of hematoma expansion. Our comprehensive research revealed the potential of intestinal flora as a potent diagnostic tool, emphasizing its significance as a preventive target for HE.

Project description:Background and purposeDelirium portends worse outcomes after intracerebral hemorrhage (ICH), but it is unclear if symptom resolution or postacute care intensity may mitigate its impact. We aimed to explore differences in outcome associated with delirium resolution before hospital discharge, as well as the potential mediating role of postacute discharge site.MethodsWe performed a single-center cohort study on consecutive ICH patients over 2 years. Delirium was diagnosed according to DSM-5 criteria and further classified as persistent or resolved based on delirium status at hospital discharge. We determined the impact of delirium on unfavorable 3-month outcome (modified Rankin Scale score, 4-6) using logistic regression models adjusted for established ICH predictors, then used mediation analysis to examine the indirect effect of delirium via postacute discharge site.ResultsOf 590 patients (mean age 70.5±15.5 years, 52% male, 83% White), 59% (n=348) developed delirium during hospitalization. Older age and higher ICH severity were delirium risk factors, but only younger age predicted delirium resolution, which occurred in 75% (161/215) of ICH survivors who had delirium. Delirium was strongly associated with unfavorable outcome, but patients with persistent delirium fared worse (adjusted odds ratio [OR], 7.3 [95% CI, 3.3-16.3]) than those whose delirium resolved (adjusted OR, 3.1 [95% CI, 1.8-5.5]). Patients with delirium were less likely to be discharged to inpatient rehabilitation than skilled nursing facilities (adjusted OR, 0.31 [95% CI, 0.17-0.59]), and postacute care site partially mediated the relationship between delirium and functional outcome in ICH survivors, leading to a 25% reduction in the effect of delirium (without mediator: adjusted OR, 3.0 [95% CI, 1.7-5.6]; with mediator: adjusted OR, 2.3 [95% CI, 1.2-4.3]).ConclusionsAcute delirium resolves in most patients with ICH by hospital discharge, which was associated with better outcomes than in patients with persistent delirium. The impact of delirium on outcomes may be further mitigated by postacute rehabilitation.

Dataset Information

Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

Publications

Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

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