Ventricle expansion rates correlate strongly with declining cognitive performance ( Carmichael et al., 2007 Nestor et al., 2008 Grimm et al., 2012 Madsen et al., 2015) and the rate of ventricle volume increase has been linked to an increase in Alzheimer’s disease (AD)-related amyloid-beta (Aβ) plaques and tau neurofibrillary tangles ( Silbert et al., 2003), as well as alterations in CSF biomarker composition. Longitudinal magnetic resonance imaging (MRI)-based studies have established that expansion of the brain’s fluid-filled lateral ventricles (LVs), or ventriculomegaly, is a defining feature of the aging brain ( Matsumae et al., 1996 Resnick et al., 2000, 2003 Scahill et al., 2003 Preul et al., 2006 Shook et al., 2014). Pathological conditions in humans that are characterized by ependymal cell stretching and/or loss, including hydrocephalus, typically result in decreased CSF turnover rates and impaired clearance of proteins and metabolites resulting in a harmful buildup of these substances in brain parenchymal tissue ( Silverberg et al., 2001, 2003 Praticò et al., 2004 Redzic et al., 2005 Johanson et al., 2008). This ependyma-mediated bidirectional CSF-ISF exchange, as well as the formation of a cell barrier to prevent movement of proteins and metabolites from the CSF back into the ISF, relies on the presence of an intact ependymal cell monolayer with motile cilia, microvilli, and tight and adherens junctions ( Del Bigio, 1995). A special epithelial lining along the ventricle walls composed of multiciliated ependymal cells allows for the movement of CSF nutrients into the brain parenchyma as well as clearance of proteins and metabolites from the interstitial fluid (ISF Johanson et al., 2008, 2011 Del Bigio, 2010). The human brain’s ventricular system is essential for the movement of nutrient-rich cerebrospinal fluid (CSF) throughout the central nervous system, providing trophic support of brain function via a wide array of vitamins, growth factors, peptides and nucleosides ( Johanson et al., 2008). These findings reveal pathophysiological outcomes associated with normal brain aging and cognitive impairment, and indicate that a multifactorial analysis is best suited to predict and monitor cognitive decline. We found that the trajectory of ventricle expansion and periventricular edema progression correlated with degree of cognitive impairment in both speed and severity, and confirmed that areas of expansion showed ventricle surface gliosis accompanied by edema and periventricular accumulation of protein aggregates, suggesting impaired clearance mechanisms in these regions.
![ventricular system of the brain ventricular system of the brain](https://i0.wp.com/brainmadesimple.com/wp-content/uploads/2019/10/Ventricular-System.png)
In collaboration with the Baltimore Longitudinal Study of Aging (BLSA) and Alzheimer’s Disease Neuroimaging Initiative (ADNI), we analyzed longitudinal structural magnetic resonance imaging (MRI) and subject-matched fluid-attenuated inversion recovery (FLAIR) MRI and periventricular biospecimens to map spatiotemporally the progression of ventricle expansion and associated periventricular edema and loss of transependymal exchange functions in healthy aging individuals and those with varying degrees of cognitive impairment. However, little is known about the interplay between age-related ventricle expansion, the decline in ependymal integrity, altered periventricular fluid homeostasis, abnormal protein accumulation and cognitive impairment. Loss of ependymal cells would compromise trans-ependymal bulk flow mechanisms required for clearance of proteins and metabolites from the brain parenchyma. Ventriculomegaly (expansion of the brain’s fluid-filled ventricles), a condition commonly found in the aging brain, results in areas of gliosis where the ependymal cells are replaced with dense astrocytic patches. 5Department of Psychological Sciences, University of Connecticut, Storrs, CT, United States.4UConn Center on Aging, University of Connecticut School of Medicine, Farmington, CT, United States.
![ventricular system of the brain ventricular system of the brain](https://i.pinimg.com/originals/a8/63/95/a8639543fae36bebefc77835e6c4a340.jpg)