ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2021
Optimized lactoferrin as a highly promising treatment for intracerebral hemorrhage: Pre-clinical experience.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed.
- Single-cell analysis of microglia and monocyte dynamics uncovers distinct TNF-driven neuroimmune signatures in humans after intracerebral hemorrhage.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Article
- Single-Cell Analysis of Microglia and Monocyte Dynamics Uncover Distinct TNF-α-driven Neuroimmune Signatures after Intracerebral Hemorrhage.bioRxiv : the preprint server for biology · 2026Article
- Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.Nature aging · 2025Article
- Biopharming of Lactoferrin: Current Strategies and Future Prospects.Pharmaceutics · 2025Review
- Lactoferrin Attenuates Pro-Inflammatory Response and Promotes the Conversion into Neuronal Lineages in the Astrocytes.International journal of molecular sciences · 2025Article
- Bioactive Self-Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Neutrophils in Intracerebral Hemorrhage: Roles, Mechanisms, and Therapeutic Implications.Mediators of inflammation · 2025Review
- Article
- A cytotoxic effect of human lactoferrin fusion with Fc domain of IgG.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Modulation of TDM-induced granuloma pathology by human lactoferrin: a persistent effect in mice.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- CNS-peripheral immune interactions in hemorrhagic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Review
- Examining the long-term effects of traumatic brain injury on fear extinction in male rats.Frontiers in behavioral neuroscience · 2023Article
- Early, Intense Rehabilitation Fails to Improve Outcome After Intra-Striatal Hemorrhage in Rats.Neurorehabilitation and neural repair · 2022Article
- Protective role of TLR9-induced macrophage/microglia phagocytosis after experimental intracerebral hemorrhage in mice.CNS neuroscience & therapeutics · 2022Article
- Microglial phagocytosis and regulatory mechanisms after stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan.Nutrients · 2022Review
- Lithium attenuates blood-brain barrier damage and brain edema following intracerebral hemorrhage via an endothelial Wnt/β-catenin signaling-dependent mechanism in mice.CNS neuroscience & therapeutics · 2022Article
- Neuron derived fractalkine promotes microglia to absorb hematoma via CD163/HO-1 after intracerebral hemorrhage.Cellular and molecular life sciences : CMLS · 2022Article
- The hallmark and crosstalk of immune cells after intracerebral hemorrhage: Immunotherapy perspectives.Frontiers in neuroscience · 2022Review
- Erythrophagocytosis by Microglia/Macrophage in Intracerebral Hemorrhage: From Mechanisms to Translation.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
Intracerebral hemorrhage (ICH) is the deadliest form of stroke for which there is no effective treatment, despite an endless number of pre-clinical studies and clinical trials. The obvious therapeutic target is the neutralization of toxic products of red blood cell (RBC) lysis that lead to cytotoxicity, inflammation, and oxidative damage. We used rigorous approaches and translationally relevant experimental ICH models to show that lactoferrin-(LTF)-based monotherapy is uniquely robust in reducing brain damage after ICH. Specifically, we designed, produced, and pharmacokinetically/toxicologically characterized an optimized LTF, a fusion of human LTF and the Fc domain of human IgG (FcLTF) that has a 5.8-fold longer half-life in the circulation than native LTF. Following dose-optimization studies, we showed that FcLTF reduces neurological injury caused by ICH in aged male/female mice, and in young male Sprague Dawley (SD) and spontaneously hypertensive rats (SHR). FcLTF showed a remarkably long 24-h therapeutic window. In tissue culture systems, FcLTF protected neurons from the toxic effects of RBCs and promoted microglia toward phagocytosis of RBCs and dead neurons, documenting its pleotropic effect. Our findings indicate that FcLTF is safe and effective in reducing ICH-induced damage in animal models used in this study.
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Registered trials
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.