ArticleNeurocritical care2018
Mannitol and Hypertonic Saline Reduce Swelling and Modulate Inflammatory Markers in a Rat Model of Intracerebral Hemorrhage.
Article in Neurocritical care, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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.
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.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- A systematic review and meta-analysis on the efficacy of glibenclamide in animal models of intracerebral hemorrhage.PloS one · 2023Pooled it
- Chemical profiling of Egregia menziesii and anti-inflammatory potential in LPS-activated RAW 264.7 macrophages.Molecular biology reports · 2026Article
- Disruption of macrophage cell volume drives inflammatory responses and type I interferon signaling.The Journal of cell biology · 2026Article
- Immunomodulatory Effects ofInternational journal of molecular sciences · 2026Article
- Influence of Culture Conditions on Bioactive Compounds inFoods (Basel, Switzerland) · 2025Review
- Article
- No Benefit of 3% Hypertonic Saline Following Experimental Intracerebral Hemorrhage.Neurotoxicity research · 2024Article
- Activation of osmo-sensitive LRRC8 anion channels in macrophages is important for micro-crystallin joint inflammation.Nature communications · 2024Article
- Cerebral edema in intracerebral hemorrhage: pathogenesis, natural history, and potential treatments from translation to clinical trials.Frontiers in stroke · 2023Review
- Expression of DEspR in acute intracerebral hemorrhage.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2022Observational
- Molecular, Pathological, Clinical, and Therapeutic Aspects of Perihematomal Edema in Different Stages of Intracerebral Hemorrhage.Oxidative medicine and cellular longevity · 2022Review
- Potentially Detrimental Effects of Hyperosmolality in Patients Treated for Traumatic Brain Injury.Journal of clinical medicine · 2021Review
- Hypertonic Sodium Lactate to Alleviate Functional Deficits Following Diffuse Traumatic Brain Injury: An Osmotic or a Lactate-Related Effect?Neurocritical care · 2021Article
- Glycerol Improves Intracerebral Hemorrhagic Brain Injury and Associated Kidney Dysfunction in Rats.Antioxidants (Basel, Switzerland) · 2021Article
- LRRC8A is essential for hypotonicity-, but not for DAMP-induced NLRP3 inflammasome activation.eLife · 2020Article
- Resuscitation Strategies for Traumatic Brain Injury.Current surgery reports · 2019Article
- Intracerebral hemorrhage induces monocyte-related gene expression within six hours: Global transcriptional profiling in swine ICH.Metabolic brain disease · 2019Article
- Particulate and solubilized β-glucan and non-β-glucan fractions ofJournal of inflammation research · 2019Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSpontaneous intracerebral hemorrhage (ICH) leaves most survivors dependent at follow-up. The importance of promoting M2-like microglial responses is increasingly recognized as a key element to ameliorate brain injury following ICH. The osmotherapeutic agents, mannitol and hypertonic saline (HTS), which are routinely used to reduce intracranial pressure, have been shown to reduce neuroinflammation in experimental ischemic and traumatic brain injury, but anti-inflammatory effects of osmotherapies have not been investigated in ICH.
methodsWe studied the effects of iso-osmotic mannitol and HTS in rat models of ICH utilizing high-dose and moderate-dose collagenase injections into the basal ganglia, associated with high and low mortality, respectively. We studied the effects of osmotherapies, first given 5 h after ICH induction, and then administered every 12 h thereafter (4 doses total). Immunohistochemistry was used to quantify microglial activation and polarization.
resultsCompared to controls, mannitol and HTS increased plasma osmolarity 1 h after infusion (301 ± 1.5, 315 ± 4.2 and 310 ± 2.0 mOsm/kg, respectively), reduced mortality at 48 h (82, 36 and 53%, respectively), and reduced hemispheric swelling at 48 h (32, 21, and 17%, respectively). In both perihematomal and contralateral tissues, mannitol and HTS reduced activation of microglia/macrophages (abundance and morphology of Iba1 + cells), and in perihematomal tissues, they reduced markers of the microglia/macrophage M1-like phenotype (nuclear p65, TNF, and NOS2), increased markers of the microglia/macrophage M2-like phenotype (arginase, YM1, and pSTAT3), and reduced infiltration of CD45 + cells.
conclusionsRepeated dosing of osmotherapeutics at regular intervals may be a useful adjunct to reduce neuroinflammation following ICH.
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