Biomechanical instability of the brain–CSF interface in hydrocephalus

Abstract

Abstract Hydrocephalus, characterized by progressive expansion of the cerebrospinal fluid (CSF)-filled ventricles (ventriculomegaly), is the most common reason for brain surgery. “Communicating” (i.e., non-obstructive) hydrocephalus is classically attributed to a primary derangement in CSF homeostasis, such as choroid plexus-dependent CSF hypersecretion, impaired cilia-mediated CSF flow currents, or decreased CSF reabsorption via the arachnoid granulations or other pathways. Emerging data suggest abnormal biomechanical properties of the brain parenchyma are an underappreciated driver of ventriculomegaly in multiple forms of communicating hydrocephalus across the lifespan. We discuss recent evidence from human and animal studies that suggests impaired neurodevelopment in congenital hydrocephalus, neurodegeneration in elderly normal pressure hydrocephalus, and, in all age groups, inflammation-related neural injury post-infectious and post-hemorrhagic hydrocephalus, can result in loss of stiffness and viscoelasticity of the brain parenchyma. Abnormal brain biomechanics creates barrier alterations at the brain-CSF interface that pathologically facilitates secondary enlargement of the ventricles, even at normal or low intracranial pressures. This “brain-centric” paradigm has implications for the diagnosis, treatment, and study of hydrocephalus from womb to tomb.