ArticleThe journal of trauma and acute care surgery2017
Early heparin administration after traumatic brain injury: Prolonged cognitive recovery associated with reduced cerebral edema and neutrophil sequestration.
Article in The journal of trauma and acute care surgery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.
What it found
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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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Compartmental Cerebrospinal Fluid Events Occurring after Subarachnoid Hemorrhage: An "Heparin Oriented" Systematic Review.International journal of molecular sciences · 2023Pooled it
- The Relationship Between Inflammation and the Development of Cerebral Ischaemia and Hypoxia in Traumatic Brain Injury-A Narrative Review.International journal of molecular sciences · 2025Review
- Sevoflurane Dampens Acute Pulmonary Inflammation via the Adenosine Receptor A2B and Heme Oxygenase-1.Cells · 2022Article
- Inhibition of CXCR4 and CXCR7 Is Protective in Acute Peritoneal Inflammation.Frontiers in immunology · 2020Article
- [Formation of gap junctions between adipose stem cells-derived Schwann cells in a rat model of dyskinesia induced by brain injury].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2019Article
- Inflammation: the link between comorbidities, genetics, and Alzheimer's disease.Journal of neuroinflammation · 2018Review
- A concomitant bone fracture delays cognitive recovery from traumatic brain injury.The journal of trauma and acute care surgery · 2018Article
- Early low-anticoagulant desulfated heparin after traumatic brain injury: Reduced brain edema and leukocyte mobilization is associated with improved watermaze learning ability weeks after injury.The journal of trauma and acute care surgery · 2018Article
- Heparin: The Silver Bullet of Aneurysmal Subarachnoid Hemorrhage?Frontiers in neurology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEarly administration of unfractionated heparin (UFH) after traumatic brain injury (TBI) reduces early in vivo circulating leukocytes (LEUs) in peri-injury penumbral brain tissue, enhancing cognitive recovery 2 days after injury. It remains unclear how long this effect lasts and if this is related to persistently accumulating LEUs in penumbral brain tissue. We hypothesized that UFH reduces LEU brain tissue sequestration resulting in prolonged cognitive recovery.
methodsCD1 male mice underwent either TBI by controlled cortical impact (CCI) or sham craniotomy. Unfractionated heparin (75 or 225 U/kg) or vehicle was repeatedly administered after TBI. Neurologic function (Garcia Neurological Test [maximum score = 18]) and body weight loss ratios were evaluated at 24 hours to 96 hours after TBI. Brain and lung wet-to-dry ratios, hemoglobin levels, and brain LEU sequestration (Ly6G immunohistochemistry) were evaluated 96 hours postmortem. Analysis of variance with Bonferroni correction determined significance (p < 0.05).
resultsCompared with untreated CCI animals (24 hours, 14.7 ± 1.0; 48 hours, 15.5 ± 0.7; 72 hours, 15.0 ± 0.8; 96 hours, 16.5 ± 0.9), UFH75 (24 hours, 16.0 ± 1.0, p < 0.01; 48 hours, 16.5 ± 0.7, p < 0.05; 72 hours, 17.1 ± 0.6, p < 0.01; 96 hours, 17.4 ± 0.7, p < 0.05) increased cognitive recovery throughout the entire observation period after TBI. At 48 hours, UFH225 significantly worsened body weight loss (10.2 ± 4.7%) as compared with uninjured animals (5.5 ± 2.9%, p < 0.05). Both UFH75 (60.8 ± 40.9 PMNs per high-power field [HPF], p < 0.05) and UFH225 (36.0 ± 17.6 PMNs/HPF, p < 0.01) significantly decreased brain neutrophil sequestration found in untreated CCI animals (124.2 ± 44.1 PMNs/HPF) 96 hours after TBI. Compared with untreated CCI animals (78.8 ± 0.8%), UFH75 (77.3 ± 0.6%, p = 0.04) reduced cerebral edema to uninjured levels (77.4 ± 0.6%, p = 0.04 vs. CCI). Only UFH225 (10.6 ± 1.2 g/dL) resulted in lower hemoglobin than in uninjured animals (13.0 ± 1.2 g/dL, p < 0.05).
conclusionsHeparin after TBI reduces tissue LEU sequestration and edema in injured brain for up to 4 days. This is associated with persistent improved cognitive recovery, but only when low-dose UFH is given. Early administration of UFH following TBI may blunt LEU-related cerebral swelling and slow progression of secondary brain injury.
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