JNNP: Secondary injury and inflammation after intracerebral hemorrhage: A systematic review and meta-analysis of molecular markers in patients’ brain tissue

Stroke caused by spontaneous intracerebral hemorrhage (ICH) can lead to a large number of deaths and disability
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There is no effective specific drug treatment for ICH

In order to determine the potential therapeutic targets of cerebral hemorrhage, a systematic review and meta-analysis of human brain tissue inflammation after cerebral hemorrhage were carried out.

Search for research related to molecular measurement of inflammation in brain tissue of ICH patients through Ovid MEDLINE and Ovid Embase databases
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No language restrictions were applied to the search, and no manual search or grey literature search was used

Search for research related to molecular measurement of inflammation in brain tissue of ICH patients through Ovid MEDLINE and Ovid Embase databases

Extract data independently from the included full text in a standardized form
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A summary measurement of the expression of molecules extracted from ICH cases, control brain tissues of ICH cases far away from hematomas, and control brain tissues of non-ICH controls

A total of 44 eligible research reports were identified for inclusion in the narrative comprehensive report of this article
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Six uncontrolled case series were included in the narrative review, but they were not included in further analysis

A total of 44 eligible research reports were identified for inclusion in the narrative comprehensive report of this article

experiment process

Only one molecule meets the criteria of a meta-analysis
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The interleukin-1β (IL-1β) protein was analyzed through three independent studies

The interleukin-1β (IL-1β) protein was analyzed through three independent studies

Document Chord Diagram

Other molecules were analyzed through multiple studies, but did not meet the meta-analysis criteria
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Five studies analyzed the subunits of the NF-κB complex 10 times and measured the abundance of mRNA and protein

Eleven studies used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) to identify double-stranded DNA breaks associated with apoptosis.
All of these studies determined that double-stranded DNA breaks increased after ICH.

Forest plot of independent correlation between IL-1β protein and cerebral hemorrhage

The preliminary finding that IL-1β protein increased more than 6 hours after intracerebral hemorrhage was supported by experimental studies, which showed that hemorrhage-induced IL-1β expression in rodent brains was associated with worse functional outcomes
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Because of the significant differences between the human cerebral hemorrhage model and the experimental cerebral hemorrhage model, interleukin-1 receptor antagonists are the subject of ongoing phase II trials of ICH treatment, supported by the consistent association between ICH and IL-1β expression The priority of IL-1β pathway modulators in the treatment of ICH
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The secondary analysis of GO enrichment revealed biological processes that may be activated or inhibited after ICH in humans
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Among the large number of genes increased after ICH, GO terms related to neutrophil degranulation and negative regulation of apoptosis are abundant
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This indicates that neutrophils accumulate in the human brain after intracerebral hemorrhage, and is supported by studies in rodent models of intracerebral hemorrhage, in which the rapid accumulation of neutrophils leads to blood-brain barrier dysfunction and neuronal damage
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Neutrophils obtained from hematomas discharged from patients with cerebral hemorrhage showed induction of pro-inflammatory genes, including IL-1β
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36 Increased peripheral blood neutrophil count is associated with poorer functional outcome 3 months after ICH
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11 studies found that compared with control tissues, TUNEL signal increased after ICH, indicating an increase in apoptosis after ICH
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The preliminary finding that IL-1β protein increased more than 6 hours after intracerebral hemorrhage was supported by experimental studies, which showed that hemorrhage-induced IL-1β expression in rodent brains was associated with worse functional outcomes
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The preliminary finding that IL-1β protein increased more than 6 hours after intracerebral hemorrhage was supported by experimental studies, which showed that hemorrhage-induced IL-1β expression in rodent brains was associated with worse functional outcomes
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In short, interleukin-1β pathway modulators can optimize the inflammatory response of ICH and are worthy of experimentation in clinical trials
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In short, interleukin-1β pathway modulators can optimize the inflammatory response of ICH and are worthy of experimentation in clinical trials
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Loan  JJ ,  Kirby  C ,  Emelianova  K Loan  JJ Loan Kirby  C Kirby Emelianova  K Emelianova , et al Secondary injury and inflammation after intracerebral haemorrhage: a systematic review and meta-analysis of molecular markers in patient brain tissue Journal of Neurology, Neurosurgery & Psychiatry  Published Online First:  06 August 2021.
  Published Online First: doi:  10.
1136/jnnp-2021-327098 doi:

 

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