Cellular insights into hydrocephalus: The diverse roles and intricate crosstalk of multiple cell types

Hydrocephalus is characterized by the abnormal accumulation of cerebrospinal fluid (CSF) within the brain's ventricular system, which can lead to ventricular dilation. This condition affects individuals across all age groups but is particularly prevalent in infants and the elderly. The etiology of hydrocephalus is multifactorial, involving excessive CSF secretion, obstruction of CSF pathways, and impairment of CSF reabsorption. Recent evidence supports the CSF permeation theory, which emphasizes the exchange of CSF with blood and interstitial fluid throughout the brain, mediated by perivascular spaces, astrocytes, and brain parenchyma. This review focuses on the role and interactions of various cell types in CSF circulation and the development of hydrocephalus, including choroid plexus cells, choroid plexus macrophages, vascular endothelial cells, neural progenitor cells, perivascular macrophages, mast cells, astrocytes, ependymal cells, and meningeal lymphatic endothelial cells(mLECs). We discuss the mechanisms by which these cells contribute to hydrocephalus, such as the disruption of blood-CSF-barrier integrity, inflammation, and alterations in CSF dynamics. Additionally, we explore potential therapeutic strategies targeting these cellular interactions, such as the inhibition of chemokine signaling and the modulation of complement pathways. Understanding the complex interplay between different cell types is crucial for developing novel treatments for hydrocephalus. This review provides a comprehensive overview of the current knowledge regarding cellular contributions to hydrocephalus and highlights areas for future research.