关键词: 脑细胞保护剂; 颅骨骨髓; 类淋巴系统; 中枢神经系统药物递送

Abstract: The blood-brain barrier (BBB) prevents peripheral pathogenic microorganisms from entering the brain, yet simultaneously blocks macromolecular and polypeptide drugs from reaching the central nervous system. Commonly used brain cytoprotective agents, such as free radical scavengers, calcium antagonists, and anti-inflammatory modulators, have demonstrated clear brain cytoprotective effects in preclinical stroke studies, yet their clinical translation has often been disappointing owing to insufficient BBB penetration. The novel drug delivery route via the skull bone marrow-cerebral dura mater-glymphatic system for intracerebral drug delivery holds promise for bypassing the BBB, offering a novel strategy for efficient brain delivery of brain cytoprotective agents. In recent years, multiple preclinical and clinical studies have progressively demonstrated that skull bone marrow administration has good feasibility, safety, and efficacy in the treatment of stroke, traumatic brain injury, and other conditions. Moreover, given the important immune surveillance function of the skull bone marrow, this route holds promise for combining multimodal delivery strategies, such as nano‑drug delivery systems and immune cell‑based drug delivery, to achieve precise and efficient intracerebral drug delivery. This review systematically summarizes recent advances in the delivery of brain cytoprotective agents via the skull bone marrow route, with a focus on the novel delivery mode of drug transport via this approach. It highlights the unique advantages of this route in bypassing the BBB, rapidly targeting cerebral lesions, and enhancing local drug concentration. 

Key words: Brain cytoprotective agent; Skull bone marrow; Glymphatic system; Central nervous system drug delivery