Comparative overview of hydrocephalus models.
| Model type | Features & mechanism | Advantages | Limitations | References |
|---|---|---|---|---|
| Genetic animal models | L1CAM, CCDC39, Rsph9, Foxj1, GemC1 mutants | Define mechanisms, mimic congenital hydrocephalus | Species-specific CSF dynamics, embryonic lethality, systemic abnormalities, and limited translation | [18–22, 24, 52, 54, 116] |
| Induced animal models | Kaolin injection, neuraminidase, intraventricular hemorrhage | Temporal control, mimic secondary hydrocephalus, reproducible | Variable phenotypes, methodology-dependent, less suited for developmental studies | [47, 61, 65–67] |
| Large animal models | Pig, dog (natural or induced hydrocephalus) | Closer ventricular size and CSF hydrodynamics to humans | Costly, ethical concerns, and fewer genetic tools | [43, 50, 68] |
| iPSC-derived organoids | Patient-derived, CRISPR-edited | Human genetic background, personalized modeling, and drug screening | Lack of vascularization and CSF flow, heterogeneity, and scalability issues | [35, 48, 49, 69, 70, 77] |
| Assembloids | Fusion of brain + vascular or choroid plexus organoids | Introduce barrier and vascular elements, model CSF interactions | Early stage, structural heterogeneity, scalability challenges | [41, 77, 134] |
| Bioengineered organ on chip | SVZ-on-chip, CSF flow chips | Dynamic CSF-like flow, biomechanical fidelity, human relevance | Fabrication complexity, standardization, and regulatory challenges | [36, 83, 84, 134, 135] |
The table summarizes major experimental platforms, detailing their origin, mechanisms, advantages, disadvantages, and representative references. In addition to traditional genetic, induced, and large-animal models, it encompasses new ones such as organoids from iPSCs, assembloids, and organ-on-chip platforms reflecting the evolution of hydrocephalus research. CSF: cerebrospinal fluid; iPSC: induced pluripotent stem cell; SVZ: subventricular zone.
IA: Conceptualization, Methodology, Investigation, Writing—original draft, Writing—review & editing, Visualization, Project administration. The author read and approved the submitted version.
The author declares that there are no competing interests.
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This review article does not contain original datasets. All information discussed is available in the published literature and cited accordingly.
This work was supported by the Hellenic Foundation for Research and Innovation (HFRI), 3rd call for postdoctoral fellows (Research Grant No. 7371). The funder had no role in study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the article for publication.
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