Age-related changes in choroid plexus and blood–cerebrospinal fluid barrier function in the sheep

Abstract

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A novel method to study cerebrospinal fluid dynamics in rats

“…Abnormally low rates of CSF formation have been linked to the accumulation of neurotoxic substances, including amyloid-β, in aging and in Alzheimer's disease (Serot et al, 2011; Serot et al, 2012; Arbel-Ornath et al, 2013). Our data showing age-dependent rates of CSF formation accorded with previous work performed in rats studied using ventriculocisternal perfusion (Preston, 2001; Chiu et al, 2012), in sheep studied using an in situ perfused choroid plexus technique (Chen et al, 2009; Chen et al, 2010), and in humans studied using MRI (Bouzerar et al, 2013). The marked age-related changes in the rates of CSF formation observed by us and others point to important upstream mechanisms in CSF regulation that are only beginning to be explored (Johanson et al, 2008).…”

“…For example, dysfunction of the CP and of the blood-cerebrospinal fluid barrier are believed to contribute to age-related cognitive decline and neurodegenerative disease (Chen et al, 2009). Abnormally low rates of CSF formation have been linked to the accumulation of neurotoxic substances, including amyloid-β, in aging and in Alzheimer's disease (Serot et al, 2011; Serot et al, 2012; Arbel-Ornath et al, 2013).…”

The Glymphatic System: A Beginner’s Guide

“…The findings that aging was associated with loss of perivascular AQP4 polarization, specifically along penetrating arterioles, and that presence of cortical parenchymal AQP4 was found to correlate with CSF-ISF exchange, suggests that the age related decline in glymphatic function might be in part attributable to dysregulation of astroglial water transport. Other factors perhaps contributing to the reduction of glymphatic activity with aging are the decline in CSF production by 66% and CSF pressure by 27% percent [70, 87, 88]. Aging is also accompanied by stiffening of the arterial wall leading to a reduction in arterial pulsatility, which is one of the drivers of glymphatic influx [70, 89].…”

Significance of Understanding Function of Glymphatic System to Manage Practical Clinical Problems of the Elderly

“…Hence, in the elderly the main pathways of water flow from cerebrospinal fluid to interstitial fluid is impaired. Furthermore, a 66% decrease in cerebrospinal fluid formation and a decrease in its pressure of 27% was noted [11,12]. One of the driving forces of glymphatic flow is the pulsatility of cerebral arterioles.…”

“…Much work has also already been devoted to the significance of impaired function of the glymphatic system in the development of dementia and other neurodegenerative diseases [7,8,9]. Some researchers have emphasized that the function of the glymphatic system is impaired in the elderly [10,11,12].…”