ArticleEBioMedicine2025
Intracalvariosseous injection: an approach for central nervous system drug delivery through skull bone marrow with a preclinical research in stroke.
Article in EBioMedicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Efficacy and safety of Y-3 intracalvariosseous injection versus intravenous injection in the treatment of acute large hemispheric infarction (SOLUTION-2): rationale and design of a multicentre, prospective, randomised, open-label, blind endpoint (PROBE) trial.Stroke and vascular neurology · 2026Article
- Adiposity measured by body roundness index is significantly associated with increased stroke prevalence: a population-based cross-sectional study.Frontiers in endocrinology · 2026Article
- Nano-flow intracalvariosseous infusion enables skull-to-brain delivery of BBB-impermeable molecular and nanoscale agents in mice and rabbits.Theranostics · 2026Article
- Immunotherapy in central nervous system tumors.International journal of surgery (London, England) · 2025Review
- Inflammation of central nervous system fiber tracts is active in patients over six months post-intracerebral hemorrhage.Acta neuropathologica communications · 2025Article
- Direct delivery of MRI contrast through skull vessel/marrow pathways into the brain guided by microCT.Theranostics · 2025Article
- Plant polysaccharides in neuroprotection: mechanistic insights across central nervous system disorders.Frontiers in pharmacology · 2025Review
- Interpreting blood-brain barrier bypass claims in reperfused stroke: a minimum reporting framework for intracalvarial immune-assisted nanoparticle delivery.Frontiers in neurologyArticle
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12 authors.
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Abstract
backgroundCentral nervous system (CNS) accessibility constitutes a major hurdle for drug development to treat neurological diseases. Existing drug delivery methods rely on breaking the blood-brain barrier (BBB) for drugs to penetrate the CNS. Researchers have discovered natural microchannels between the skull bone marrow and the dura mater, providing a pathway for drug delivery through the skull bone marrow. However, there has been no research on the feasibility, safety, and efficacy of this delivery method for drug treatment of stroke.
methodsWe used a microporous method for intracalvariosseous (ICO) injection to deliver drugs directly into brain parenchyma through skull bone marrow. Safety of ICO was assessed by monitoring changes in skull and peripheral blood neutrophil counts, and FITC-dextran extravasation across the BBB. Drug delivery pathways were observed through transparent skull-dura mater-brain tissue. In a rodent stroke model, NA-1 or Y-3 neuroprotective agents were administered via ICO to evaluate safety and efficacy by assessing neurological deficits, infarct size, neuroinflammatory factors, neuronal apoptosis, and liver/kidney function. Drug concentration in tissues was measured using fluorescence tracing and high-performance liquid chromatography to gauge ICO delivery efficiency.
findingsICO injection delivers drugs to the brain parenchyma through microchannels between the skull bone marrow and the dura mater, offering higher delivery efficiency than intravenous injection. After ICO injection, there were no changes in neutrophil counts in the skull bone marrow and peripheral blood, and the amount of FITC-dextran passing through the BBB remained unchanged. This confirmed that ICO injection does not cause skull infection or break BBB, which suggested ICO injection is safe and feasible. In the treatment of stroke with neuroprotective agents, although the drug dosage of ICO injection was lower than intravenous injection, drug accumulation in the brain increased after ICO injection, which helped repair nerve damage, reduce neuronal apoptosis, and decrease the expression of inflammatory factors.
interpretationICO injection is a central nervous system drug delivery method that utilizes natural microchannels between the skull and dura mater for efficient drug delivery. Our results assessed the feasibility and safety of ICO injection at the preclinical level and evaluated its efficacy in animal models of stroke. The findings provided a foundation for the clinical translation of ICO injection.
fundingThis study was supported by The National Natural Science Foundation of China (No. 82425101); Beijing Municipal Science & Technology Commission (No. Z231100004823036); Capital's Funds for Health Improvement and Research (2022-2-2045); National Key Research & Development Program of China (2022YFF1501500, 2022YFF1501501, 2022YFF1501502, 2022YFF1501503, 2022YFF1501504, 2022YFF1501505).
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