经颅骨骨髓-硬脑膜-类淋巴系统绕道血脑屏障的药物递送

doi:10.3969/j.issn.1006-7795.2026.01.002

首都医科大学学报

经颅骨骨髓-硬脑膜-类淋巴系统绕道血脑屏障的药物递送

张眉扬,陈壮壮,王楠星,姬若冰,杨沫,王伊龙^*

首都医科大学附属北京天坛医院神经病学中心，北京 100070

收稿日期:2025-11-03 修回日期:2025-11-26 出版日期:2026-02-21 发布日期:2026-01-20
通讯作者: 王伊龙 E-mail:yilong528@aliyun.com
基金资助:
国家自然科学基金杰出青年科学基金项目（82425101），癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项(2023ZD0504800, 2023ZD0504801, 2023ZD0504802, 2023ZD0504803, 2023ZD0504804)，北京市科技计划项目（Z231100004823036），首都医学科学创新中心资助项目(CX25YZ07)，首都卫生发展科研专项项目（首发-2022-2-2045），国家重点研发计划项目（2024YFC3044800，2022YFF1501500，2022YFF1501501，2022YFF1501502，2022YFF1501503，2022YFF1501504，2022YFF1501505）。

Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system

Zhang Meiyang, Chen Zhuangzhuang, Wang Nanxing, Ji Ruobing, Yang Mo, Wang Yilong^*

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070, China

Received:2025-11-03 Revised:2025-11-26 Online:2026-02-21 Published:2026-01-20
Supported by:
This study was supported by National Natural Science Foundation of China (82425101), Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0504800, 2023ZD0504801, 2023ZD0504802, 2023ZD0504803, 2023ZD0504804), Beijing Municipal Science & Technology Commission(Z231100004823036）, A Grant from the Chinese Institutes for Medical Research, Beijing(CX25YZ07), Capital's Funds for Health Improvement and Research(2022-2-2045), National Key Research and Development Program of China(2024YFC3044800, 2022YFF1501500, 2022YFF1501501, 2022YFF1501502, 2022YFF1501503, 2022YFF1501504, 2022YFF1501505).

摘要/Abstract

摘要： 生理状态下，血脑屏障的存在阻碍了95%以上的各类药物进入中枢神经系统。如何微创或无创地突破血脑屏障的限制，实现精准高效的颅内药物递送是目前医药研发领域的难点之一。本文旨在综述经过经颅骨骨髓-硬脑膜-类淋巴系统新途径实现绕道血脑屏障的中枢神经系统药物递送的可行性与有效性，以期为多种脑重大疾病的药物递送及治疗提供新的视角与策略。

关键词: 中枢神经系统药物递送, 经颅骨骨髓给药, 血脑屏障, 类淋巴系统, 免疫监视, 脑-骨髓轴, 颅骨骨髓免疫

Abstract: Under physiological conditions, the blood-brain barrier (BBB) blocks over 95% of various drugs from entering the central nervous system (CNS). How to achieve precise and efficient intracranial drug delivery by overcoming the BBB in a minimally invasive or non-invasive manner has become one of the current challenges in pharmaceutical research and development. This review summaries the feasibility and efficacy of a novel CNS drug delivery pathway that bypasses the BBB through the skull bone marrow-dura-glymphatic system, to provide new perspectives and strategies for drug delivery and treatment in a range of major brain diseases.

Key words: central nervous system drug delivery, intracalvariosseous drug administration, blood-brain barrier, glymphatic system, immunological surveillance, brain-bone marrow axis, skull bone marrow immunity

中图分类号:

R743

张眉扬, 陈壮壮, 王楠星, 姬若冰, 杨沫, 王伊龙. 经颅骨骨髓-硬脑膜-类淋巴系统绕道血脑屏障的药物递送[J]. 首都医科大学学报, doi: 10.3969/j.issn.1006-7795.2026.01.002.

Zhang Meiyang, Chen Zhuangzhuang, Wang Nanxing, Ji Ruobing, Yang Mo, Wang Yilong. Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2026.01.002.

参考文献

［1］Li X Y, Kong X M, Yang C H, et al. Global, regional, and national burden of ischemic stroke, 1990－2021: an analysis of data from the global burden of disease study 2021［J］. EClinicalMedicine, 2024, 75: 102758.
［2］Pedder J H, Sonabend A M, Cearns M D, et al. Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease［J］. Lancet Neurol, 2025, 24(3): 246－260.
［3］Nance E, Pun S H, Saigal R, et al. Drug delivery to the central nervous system［J］. Nat Rev Mater, 2022, 7(4): 314－331.
［4］Wu D, Chen Q, Chen X J, et al. The blood-brain barrier: structure, regulation, and drug delivery［J］. Signal Transduct Target Ther, 2023, 8(1): 217.
［5］Khang M, Bindra R S, Mark Saltzman W. Intrathecal delivery and its applications in leptomeningeal disease［J］. Adv Drug Deliv Rev, 2022, 186: 114338.
［6］Meng Y, Goubran M, Rabin J S, et al. Blood-brain barrier opening of the default mode network in Alzheimer's disease with magnetic resonance-guided focused ultrasound［J］. Brain, 2023, 146(3): 865－872.
［7］Nong J, Glassman P M, Myerson J W, et al. Targeted nanocarriers co-opting pulmonary intravascular leukocytes for drug delivery to the injured brain［J］. ACS Nano, 2023, 17(14): 13121－13136.
［8］Rust R, Yin H, Achón Buil B, et al. The blood-brain barrier: a help and a hindrance［J］. Brain, 2025, 148(7): 2262－2282.
［9］Cugurra A, Mamuladze T, Rustenhoven J, et al. Skull and vertebral bone marrow are myeloid cell reservoirs for the meninges and CNS parenchyma［J］. Science, 2021, 373(6553): eabf7844.
［10］Pinho-Correia L M, McCullough S J C, Ghanizada H, et al. CSF transport at the brain-meningeal border: effects on neurological health and disease［J］. Lancet Neurol, 2025, 24(6): 535－547.
［11］Liu W Q, Yang M, Wang N X, et al. Intracalvariosseous injection: an approach for central nervous system drug delivery through skull bone marrow with a preclinical research in stroke［J］. EBioMedicine, 2025, 112: 105568.
［12］Kwon D. Guardians of the brain: how a special immune system protects our grey matter［J］. Nature, 2022, 606(7912): 22－24.
［13］Herisson F, Frodermann V, Courties G, et al. Direct vascular channels connect skull bone marrow and the brain surface enabling myeloid cell migration［J］. Nat Neurosci, 2018, 21(9): 1209－1217.
［14］Brioschi S, Wang W L, Peng V, et al. Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS Borders［J］. Science, 2021, 373(6553): eabf9277.
［15］Pulous F E, Cruz-Hernández J C, Yang C B, et al. Cerebrospinal fluid can exit into the skull bone marrow and instruct cranial hematopoiesis in mice with bacterial meningitis［J］. Nat Neurosci, 2022, 25(5): 567－576.
［16］Mazzitelli J A, Smyth L C D, Cross K A, et al. Cerebrospinal fluid regulates skull bone marrow niches via direct access through dural channels［J］. Nat Neurosci, 2022, 25(5): 555－560.
［17］Yang M, Li Y X, Shi K B, et al. Single-cell transcriptomes of immune cells from multiple compartments redefine the ontology of myeloid subtypes post-stroke［J］. Adv Sci, 2025, 12(13): e2408722.
［18］Kang J H, Yang J K, Cho K H, et al. Intracalvariosseous administration of donepezil microspheres protects against cognitive impairment by virtue of long-lasting brain exposure in mice［J］. Theranostics, 2024, 14(17): 6708－6725.
［19］Kang J H, Ko Y T. Intraosseous administration into the skull: potential blood-brain barrier bypassing route for brain drug delivery［J］. Bioeng Transl Med, 2022, 8(2): e10424.
［20］Dubey A, Yamashita E, Stangeland B, et al. Brain tumors induce widespread disruption of calvarial bone and alteration of skull marrow immune landscape［J］. Nat Neurosci, 2025, 28(11): 2231－2246.
［21］Kigar S L, Lynall M E, DePuyt A E, et al. Chronic social defeat stress induces meningeal neutrophilia via type I interferon signaling in male mice［J］. Nat Commun, 2025, 16(1): 8153.
［22］Wang N X, Zhang M Y, Yang M, et al. 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［J/OL］. Stroke Vasc Neurol, 2025: svn－2024－004011. (2025－06－03)［2025－10－20］. https://pubmed.ncbi.nlm.nih.gov/40461153/.
［23］Weiser G, Hoffmann Y, Galbraith R, et al. Current advances in intraosseous infusion-a systematic review［J］. Resuscitation, 2012, 83(1): 20－26.

经颅骨骨髓-硬脑膜-类淋巴系统绕道血脑屏障的药物递送

Bypassing the blood-brain barrier: a novel drug delivery pathway via the skull bone marrow-dura-glymphatic system

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