Ventricular and Periventricular Anomalies in the Aging and Cognitively Impaired Brain

Abstract

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. Loss of ependymal cells would compromise trans-ependymal bulk flow mechanisms required for clearance of proteins and metabolites from the brain parenchyma. 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. 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. 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. 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.

Characterization of the ventricular-subventricular stem cell niche during human brain development

“…3A,B). Semi-automated segmentation using ITK-SNAP (Shook et al, 2014;Snippert et al, 2010;Todd et al, 2017;Yushkevich et al, 2006) followed by 3D reconstruction of the lateral ventricles and whole brain using 3D Slicer (Acabchuk et al, 2015;Shook et al, 2014) revealed that the average total brain volume increases rapidly from 15 gw to 1 year. Regression analysis predicts that from 19 gw to birth, the brain grows at a nearly linear rate of 1.2×10 6 mm 3 /year (23 cm 3 /week) and from birth to 1 year at 5.5×10 5 mm 3 /year (11 cm 3 /week) (see also Kinoshita et al, 2001).…”

“…Regions corresponding to the LGE in fetal tissue and the lateral wall of the lateral ventricle in postnatal tissue were dissected and sectioned coronally at 100 mm thickness. Immunohistochemistry was performed as described (Todd et al, 2017) using the following antibodies: goat polyclonal anti-GFAP (1:250; Abcam, #ab53554), mouse monoclonal anti-FOXJ1 (1:250; Invitrogen, #14-9965-80), guinea pig anti-doublecortin (DCX) (1:1000, EMD Millipore, #AB2253) and rabbit anti-Ki67 (1:1000; Novocastra, #6013874). Alexa Fluor dye-conjugated polyclonal secondary antibodies (1:500) were used: donkey anti-mouse 405 (Abcam, #ab175658), donkey anti-mouse 488 (Invitrogen, #21202), donkey antirabbit 546 (Invitrogen, #A10040), donkey anti-goat-647 (Invitrogen, #A21447) and donkey anti-rat 647 (Invitrogen, #A18744).…”

“…loni.usc.edu, 7T MRI scanner) and Yale School of Medicine (3T MRI scanner) (Table 1). Lateral ventricle and whole-brain semi-automated segmentation and volume/surface area analyses were completed using ITK-SNAP and 3D Slicer software as previously described (Acabchuk et al, 2015;Todd et al, 2017). To determine accurate whole-brain volume and surface area measurements, skulls were digitally removed from MRI scans using Brain Suite software (www.brainsuite.org).…”

Brain ependymocytes in neurogenesis and maintaining integrity of blood-cerebrospinal fluid barrier

“…Роль эпендимоцитов в нейрогенезе В последние годы достаточно широко обсуждается вопрос участия эпендимальных клеток в нейрогенезе. Однако факт того, что в боковых желудочках взрослого человека отсутствуют эпендимальные клетки, позволяет предположить, что эпендимоциты в нейроге-ОБЗОРНЫЕ СТАТЬИ ® незе участвуют ограниченно, только во внутриутробном периоде развития ЦНС [17][18][19][20].…”

Lateral ventricle volume trajectories predict response inhibition in older age - a longitudinal brain imaging and machine learning approach

“…The choice of LV volumes is further supported by studies describing the brain’s fluid-filled ventricles as a biomarker of the aging brain [27–29], and studies linking age-related ventricular expansion to changes in cognitive function at a subject-specific level [30–32]. A study by Todd et al [33] showed a strong linear relationship between LV volume expansion and worsening of cognitive performance over a two-years period. The study assessed cognitive function by tests primarily designed to reveal symptoms of major neurocognitive disorders.…”