ArticleThe journal of trauma and acute care surgery2018
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.
Article in The journal of trauma and acute care surgery, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed, 14 citations in OpenAlex.
- Emerging Role, Molecular Mechanisms, and Therapeutic Potential of 2-O, 3-O Desulfated Heparin (ODSH) Across Inflammatory and Vascular Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Persistent Blunting of Penumbral Leukocyte Mobilization by Beta Blockade Administered for Two Weeks After Traumatic Brain Injury.The Journal of surgical research · 2022Article
- Article
- Multi-target approaches to CNS repair: olfactory mucosa-derived cells and heparan sulfates.Nature reviews. Neurology · 2020Review
- An inflammatory pulmonary insult post-traumatic brain injury worsens subsequent spatial learning and neurological outcomes.The journal of trauma and acute care surgery · 2019Article
- Article
- Review
- Leukocyte Heparanase: A Double-Edged Sword in Tumor Progression.Frontiers in oncology · 2019Review
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundUnfractionated heparin administered immediately after traumatic brain injury (TBI) reduces brain leukocyte (LEU) accumulation, and enhances early cognitive recovery, but may increase bleeding after injury. It is unknown how non-anticoagulant heparins, such as 2,3-O desulfated heparin (ODSH), impact post-TBI cerebral inflammation and long-term recovery. We hypothesized that ODSH after TBI reduces LEU-mediated brain inflammation and improves long-term neurologic recovery.
methodsCD1 male mice (n = 66) underwent either TBI (controlled cortical impact [CCI]) or sham craniotomy. 2,3-O desulfated heparin (25 mg/kg [25ODSH] or 50 mg/kg [50ODSH]) or saline was administered for 48 hours after TBI in 46 animals. At 48 hours, intravital microscopy visualized rolling LEUs and fluorescent albumin leakage in the pial circulation, and the Garcia Neurologic Test assessed neurologic function. Brain edema (wet/dry ratio) was evaluated post mortem. In a separate group of animals (n = 20), learning/memory ability (% time swimming in the Probe platform quadrant) was assessed by the Morris Water Maze 17 days after TBI. Analysis of variance with Bonferroni correction determined significance (p < 0.05).
resultsCompared with CCI (LEU rolling: 32.3 ± 13.7 LEUs/100 μm per minute, cerebrovascular albumin leakage: 57.4 ± 5.6%), both ODSH doses reduced post-TBI pial LEU rolling (25ODSH: 18.5 ± 9.2 LEUs/100 μm per minute, p = 0.036; 50ODSH: 7.8 ± 3.9 LEUs/100 μm per minute, p < 0.001) and cerebrovascular albumin leakage (25ODSH: 37.9 ± 11.7%, p = 0.001, 50ODSH: 32.3 ± 8.7%, p < 0.001). 50ODSH also reduced injured cerebral hemisphere edema (77.7 ± 0.4%) vs. CCI (78.7 ± 0.4 %, p = 0.003). Compared with CCI, both ODSH doses improved Garcia Neurologic Test at 48 hours. Learning/memory ability (% time swimming in target quadrant) was lowest in CCI (5.9 ± 6.4%) and significantly improved in the 25ODSH group (27.5 ± 8.2%, p = 0.025).
conclusion2,3-O desulfated heparin after TBI reduces cerebral LEU recruitment, microvascular permeability and edema. 2,3-O desulfated heparin may also improve acute neurologic recovery leading to improved learning/memory ability weeks after injury.
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Registered trials
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