Evidence map›Paper›PMID 34671423›Full record

ReviewTherapeutic advances in neurological disorders2021

Secondary mechanisms of injury and viable pathophysiological targets in intracerebral hemorrhage.

Wendy Bautista, P David Adelson, Nathan Bicher, Marios Themistocleous, Georgios Tsivgoulis, Jason J Chang

Open access · goldAbstract readReview
In one paragraph

Review in Therapeutic advances in neurological disorders, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.

  1. Pooled it
  2. Early neurological improvement with deferoxamine after intracerebral hemorrhage: A post hoc analysis of the i-DEF trial.International journal of stroke : official journal of the International Stroke Society · 2025
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  15. Intraparenchymal B cell therapy protects neurological function and modulates local neuroinflammation in experimental hemorrhagic stroke.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 6 institutions in 2 countries.

Wendy BautistaCenter for Advanced Preclinical Research (CAPR), National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
P David AdelsonDivision of Pediatric Neurosurgery, Department of Child Health, Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ, USA.
Nathan BicherDepartment of Neurology, Georgetown University Medical Center, Washington, DC, USA.
Marios ThemistocleousDepartment of Neurosurgery, Pediatric Hospital of Athens, Agia Sophia, Athens, Greece.
Georgios TsivgoulisDepartment of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA.ORCID https://orcid.org/0000-0002-0640-3797
Jason J ChangDepartment of Critical Care Medicine, MedStar Washington Hospital Center, 110 Irving Street, NW, Rm 4B42, Washington, DC 20010, USA.ORCID https://orcid.org/0000-0002-0825-3008
Barrow Neurological Institute · USChildren's Hospital Agia Sophia · GRGeorgetown University · USMedStar Washington Hospital Center · USNational Institutes of Health · USUniversity of Tennessee Health Science Center · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Intracerebral hemorrhage (ICH) can be divided into a primary and secondary phase. In the primary phase, hematoma volume is evaluated and therapies are focused on reducing hematoma expansion. In the secondary, neuroprotective phase, complex systemic inflammatory cascades, direct cellular toxicity, and blood-brain barrier disruption can result in worsening perihematomal edema that can adversely affect functional outcome. To date, all major randomized phase 3 trials for ICH have targeted primary phase hematoma volume and incorporated clot evacuation, intensive blood pressure control, and hemostasis. Reasons for this lack of clinical efficacy in the major ICH trials may be due to the lack of therapeutics involving mitigation of secondary injury and inflexible trial design that favors unilateral mechanisms in a complex pathophysiology. Potential pathophysiological targets for attenuating secondary injury are highlighted in this review and include therapies increasing calcium, antagonizing microglial activation, maintaining macrophage M1 versus M2 balance by decreasing M1 signaling, aquaporin inhibition, NKCCl inhibition, endothelin receptor inhibition, Sur1-TRPM4 inhibition, matrix metalloproteinase inhibition, and sphingosine-1-phosphate receptor modulation. Future clinical trials in ICH focusing on secondary phase injury and, potentially implementing adaptive trial design approaches with multifocal targets, may improve insight into these mechanisms and provide potential therapies that may improve survival and functional outcome.

Indexed as

intracerebral hemorrhageneuroprotectionperihematomal edemasecondary injuryvasogenic edema

Identifiers

PMID34671423
PMCPMC8521409
OpenAlexW3205026092

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.