Rethinking the cilia hypothesis of hydrocephalus
Dysfunction of motile cilia in ependymal cells has been proposed to be a pathogenic cause of cerebrospinal fluid (CSF) overaccumulation leading to ventricular expansion in hydrocephalus, primarily based on observations of enlarged ventricles in mouse models of primary ciliary dyskinesia. Here, we re...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996122003059 |
| _version_ | 1798006596840718336 |
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| author | Phan Q. Duy Ana B.W. Greenberg William E. Butler Kristopher T. Kahle |
| author_facet | Phan Q. Duy Ana B.W. Greenberg William E. Butler Kristopher T. Kahle |
| author_sort | Phan Q. Duy |
| collection | DOAJ |
| description | Dysfunction of motile cilia in ependymal cells has been proposed to be a pathogenic cause of cerebrospinal fluid (CSF) overaccumulation leading to ventricular expansion in hydrocephalus, primarily based on observations of enlarged ventricles in mouse models of primary ciliary dyskinesia. Here, we review human and animal evidence that warrants a rethinking of the cilia hypothesis in hydrocephalus. First, we discuss neuroembryology and physiology data that do not support a role for ependymal cilia as the primary propeller of CSF movement across the ventricles in the human brain, particularly during in utero development prior to the functional maturation of ependymal cilia. Second, we highlight that in contrast to mouse models, motile ciliopathies infrequently cause hydrocephalus in humans. Instead, gene mutations affecting motile cilia function impact not only ependymal cilia but also motile cilia found in other organ systems outside of the brain, causing a clinical syndrome of recurrent respiratory infections and situs inversus, symptoms that do not typically accompany most cases of human hydrocephalus. Finally, we postulate that certain cases of hydrocephalus associated with ciliary gene mutations may arise not necessarily just from loss of cilia-generated CSF flow but also from altered neurodevelopment, given the potential functions of ciliary genes in signaling and neural stem cell fate beyond generating fluid flow. Further investigations are needed to clarify the link between motile cilia, CSF physiology, and brain development, the understanding of which has implications for the care of patients with hydrocephalus and other related neurodevelopmental disorders. |
| first_indexed | 2024-04-11T12:57:10Z |
| format | Article |
| id | doaj.art-605b8a6ac3a04921a5d5704d5343edcf |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-04-11T12:57:10Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-605b8a6ac3a04921a5d5704d5343edcf2022-12-22T04:23:03ZengElsevierNeurobiology of Disease1095-953X2022-12-01175105913Rethinking the cilia hypothesis of hydrocephalusPhan Q. Duy0Ana B.W. Greenberg1William E. Butler2Kristopher T. Kahle3Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT, USA; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT, USA; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USADepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USADepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USADepartment of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital, Boston, MA, USA; Corresponding author at: Department of Neurosurgery, Massachusetts General Hospital, Boston, MA, USA.Dysfunction of motile cilia in ependymal cells has been proposed to be a pathogenic cause of cerebrospinal fluid (CSF) overaccumulation leading to ventricular expansion in hydrocephalus, primarily based on observations of enlarged ventricles in mouse models of primary ciliary dyskinesia. Here, we review human and animal evidence that warrants a rethinking of the cilia hypothesis in hydrocephalus. First, we discuss neuroembryology and physiology data that do not support a role for ependymal cilia as the primary propeller of CSF movement across the ventricles in the human brain, particularly during in utero development prior to the functional maturation of ependymal cilia. Second, we highlight that in contrast to mouse models, motile ciliopathies infrequently cause hydrocephalus in humans. Instead, gene mutations affecting motile cilia function impact not only ependymal cilia but also motile cilia found in other organ systems outside of the brain, causing a clinical syndrome of recurrent respiratory infections and situs inversus, symptoms that do not typically accompany most cases of human hydrocephalus. Finally, we postulate that certain cases of hydrocephalus associated with ciliary gene mutations may arise not necessarily just from loss of cilia-generated CSF flow but also from altered neurodevelopment, given the potential functions of ciliary genes in signaling and neural stem cell fate beyond generating fluid flow. Further investigations are needed to clarify the link between motile cilia, CSF physiology, and brain development, the understanding of which has implications for the care of patients with hydrocephalus and other related neurodevelopmental disorders.http://www.sciencedirect.com/science/article/pii/S0969996122003059HydrocephalusCerebrospinal fluidVentriclesEpendymal cellsCiliaPrimary ciliary dyskinesia |
| spellingShingle | Phan Q. Duy Ana B.W. Greenberg William E. Butler Kristopher T. Kahle Rethinking the cilia hypothesis of hydrocephalus Neurobiology of Disease Hydrocephalus Cerebrospinal fluid Ventricles Ependymal cells Cilia Primary ciliary dyskinesia |
| title | Rethinking the cilia hypothesis of hydrocephalus |
| title_full | Rethinking the cilia hypothesis of hydrocephalus |
| title_fullStr | Rethinking the cilia hypothesis of hydrocephalus |
| title_full_unstemmed | Rethinking the cilia hypothesis of hydrocephalus |
| title_short | Rethinking the cilia hypothesis of hydrocephalus |
| title_sort | rethinking the cilia hypothesis of hydrocephalus |
| topic | Hydrocephalus Cerebrospinal fluid Ventricles Ependymal cells Cilia Primary ciliary dyskinesia |
| url | http://www.sciencedirect.com/science/article/pii/S0969996122003059 |
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