A neural stem cell paradigm of pediatric hydrocephalus.

Autor:	Duy PQ; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA.; Medical Scientist Training Program, Yale University School of Medicine, New Haven, CT 06510, USA.; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA., Rakic P; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA., Alper SL; Division of Nephrology and Vascular Biology Research Center, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, MA 02215, USA., Robert SM; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA., Kundishora AJ; Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA., Butler WE; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA., Walsh CA; Division of Genetics and Genomics, Manton Center for Orphan Disease Research, Department of Pediatrics, and Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA 02115, USA.; Departments of Pediatrics and Neurology, Harvard Medical School, Boston, MA 02115, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA., Sestan N; Department of Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA., Geschwind DH; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA., Jin SC; Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA., Kahle KT; Department of Neurosurgery, Massachusetts General Hospital, Boston, MA 02114, USA.; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.; Harvard Center for Hydrocephalus and Neurodevelopmental Disorders, Massachusetts General Hospital, Boston, MA 02114, USA.
Jazyk:	angličtina
Zdroj:	Cerebral cortex (New York, N.Y. : 1991) [Cereb Cortex] 2023 Apr 04; Vol. 33 (8), pp. 4262-4279.
DOI:	10.1093/cercor/bhac341
Abstrakt:	Pediatric hydrocephalus, the leading reason for brain surgery in children, is characterized by enlargement of the cerebral ventricles classically attributed to cerebrospinal fluid (CSF) overaccumulation. Neurosurgical shunting to reduce CSF volume is the default treatment that intends to reinstate normal CSF homeostasis, yet neurodevelopmental disability often persists in hydrocephalic children despite optimal surgical management. Here, we discuss recent human genetic and animal model studies that are shifting the view of pediatric hydrocephalus from an impaired fluid plumbing model to a new paradigm of dysregulated neural stem cell (NSC) fate. NSCs are neuroprogenitor cells that comprise the germinal neuroepithelium lining the prenatal brain ventricles. We propose that heterogenous defects in the development of these cells converge to disrupt cerebrocortical morphogenesis, leading to abnormal brain-CSF biomechanical interactions that facilitate passive pooling of CSF and secondary ventricular distention. A significant subset of pediatric hydrocephalus may thus in fact be due to a developmental brain malformation leading to secondary enlargement of the ventricles rather than a primary defect of CSF circulation. If hydrocephalus is indeed a neuroradiographic presentation of an inborn brain defect, it suggests the need to focus on optimizing neurodevelopment, rather than CSF diversion, as the primary treatment strategy for these children. (© The Author(s) 2022. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu