Scientific American May 2021 pp42-47 | Neuroscience|”Holes In The Shield” “Leaks in a protective filter called the blood-brain barrier may lead to Alzheimer’s and other dementias. Reversing the effects makes aging animal brains look young and healthy” By Daniela Kaufer and Alon Friedman.
Image from eurekalert.org
Read the article for all detail. Also see the author’s paper in Science Translational Medicine published in 2019
Summary provided by 2244
Our recent readings in Neuroscience have struck on brain inflammation as a key component of Alzheimer’s and other dementias. This article presents research of Daniela Kaufer (UC Berkeley), Alon Friedman (Dalhousie University), Barry Hart (Innovation Pathways-Palo Alto) and others showing that after traumatic brain injury and in time with animal and human aging that Blood-Brain-Barrier (BBB) begins to breakdown and lose the function of it’s selective barrier. In health, the BBB allows the passage of needed substances like glucose and oxygen but blocks larger molecules like proteins and also restricts microbes from entering the brain.
Using animal and human imaging studies, these researchers to their surprise and dismay found that albumin, one of the most abundant circulating proteins, is a likely culprit contributing to at least some of the pathology and functional deficits associated with brain inflammation. As albumin from the blood enters the brain “it appears to stimulate astrocytes”, [Astrocytes are one of several cell types that support neurons], by binding to cell receptors for transforming growth factor beta (TGF beta) and setting off inflammation that’s is mediated by “many damaging chemicals.” A controlled amount of inflammation in the body or brain is helpful in promoting healing of damaged tissue but unchecked can be damaging.
Experiments testing this albumin-hypothesis have demonstrated a correlation between albumin's presence, damage in the hippocampus and a reduced ability of mice to navigate maze challenges. The hippocampus is a brain area that is important for memory and key to the ability of mice to navigate a maze. Using MRI, other researchers “such as Berislav V. Ziokovic (USC-Keck School of Medicine), “show[ed] barrier deterioration in aging people with cognitive impairment.” Kaufer and Friedman, performed autopsy studies, that demonstrated that “heightened albumin levels accompany greater amounts of TGF-beta, always in astrocytes. With these findings, the team used genetic mice without TGF-beta receptors and demonstrated that these mice when challenged with albumin subsequently have “low levels of inflammation" and that these mice performed well in maze studies.
Based on these findings, Barry Hart (Innovation Pathways) started collaborating with Kaufer and Friedman, suggesting that investigations evaluate an anti-cancer drug IBW that was designed “specifically…[to block] the activity of the TGFB receptor. Mice with BBB damage showed restored brain tissue and “within days…the treated mice were almost as good at learning the maze as rodents half their age.” Such a “brain rejuvenation” is particularly promising as this suggests “the aging brain has a hidden capacity to rebound from some types of insults.”
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