MRI detects blood-brain barrier alterations in a rat model of Alzheimer’s disease and lung infection

Yolanda Ohene; William J. Morrey; Elizabeth   Powell; Katherine  F.   Smethers; Nadim Luka; Kieron South; Michael Berks; Catherine B. Lawrence; Geoffrey J. M. Parker; Laura M. Parkes; Hervé Boutin; Ben R. Dickie

MRI detects blood-brain barrier alterations in a rat model of Alzheimer’s disease and lung infection

Yolanda Ohene, William J. Morrey, Elizabeth Powell , Katherine F. Smethers, Nadim Luka, Kieron South, Michael Berks, Catherine B. Lawrence, Geoffrey J. M. Parker, Laura M. Parkes, Hervé Boutin, Ben R. Dickie

University of Manchester (UOM)

Research output: Contribution to journal › Article › peer-review

Abstract

Pneumonia is a common infection in people suffering with Alzheimer’s disease, leading to delirium, critical illness or severe neurological decline, which may be due to an amplified response of the blood-brain barrier (BBB) to peripheral insult. We assess the response of the BBB to repeated Streptococcus pneumoniae lung infection in rat model of Alzheimer’s disease (TgF344-AD), at 13- and 18-months old, using dynamic contrast-enhanced (DCE) MRI and filter exchange imaging. Higher BBB water exchange rate is initially detected in infected TgF344-AD rats. BBB water exchange rates correlated with hippocampus aquaporin-4 water channel expression in infected animals. We detected no differences in BBB permeability to gadolinium contrast agent measured by DCE-MRI, confirmed by staining for tight junction proteins, occludin and claudin-5. These findings provide insight into the mechanisms of how peripheral inflammation impacts the BBB.

Original language	English
Journal	npj Imaging
Publication status	Accepted/In press - 23 Jan 2025

Keywords

Alzheimer’s disease
Aquaporin-4
Blood-brain barrier
Lung infection
Neuroinflammation
Water-exchange MRI

Cite this

@article{9c0b377e2f7945fdb87db29e4102afbb,

title = "MRI detects blood-brain barrier alterations in a rat model of Alzheimer{\textquoteright}s disease and lung infection",

abstract = "Pneumonia is a common infection in people suffering with Alzheimer{\textquoteright}s disease, leading to delirium, critical illness or severe neurological decline, which may be due to an amplified response of the blood-brain barrier (BBB) to peripheral insult. We assess the response of the BBB to repeated Streptococcus pneumoniae lung infection in rat model of Alzheimer{\textquoteright}s disease (TgF344-AD), at 13- and 18-months old, using dynamic contrast-enhanced (DCE) MRI and filter exchange imaging. Higher BBB water exchange rate is initially detected in infected TgF344-AD rats. BBB water exchange rates correlated with hippocampus aquaporin-4 water channel expression in infected animals. We detected no differences in BBB permeability to gadolinium contrast agent measured by DCE-MRI, confirmed by staining for tight junction proteins, occludin and claudin-5. These findings provide insight into the mechanisms of how peripheral inflammation impacts the BBB.",

keywords = "Alzheimer{\textquoteright}s disease, Aquaporin-4, Blood-brain barrier, Lung infection, Neuroinflammation, Water-exchange MRI",

author = "Yolanda Ohene and Morrey, {William J.} and Elizabeth Powell and Smethers, {Katherine F.} and Nadim Luka and Kieron South and Michael Berks and Lawrence, {Catherine B.} and Parker, {Geoffrey J. M.} and Parkes, {Laura M.} and Herv{\'e} Boutin and Dickie, {Ben R.}",

year = "2025",

month = jan,

day = "23",

language = "English",

}

TY - JOUR

T1 - MRI detects blood-brain barrier alterations in a rat model of Alzheimer’s disease and lung infection

AU - Ohene, Yolanda

AU - Morrey, William J.

AU - Powell , Elizabeth

AU - Smethers, Katherine F.

AU - Luka, Nadim

AU - South, Kieron

AU - Berks, Michael

AU - Lawrence, Catherine B.

AU - Parker, Geoffrey J. M.

AU - Parkes, Laura M.

AU - Boutin, Hervé

AU - Dickie, Ben R.

PY - 2025/1/23

Y1 - 2025/1/23

N2 - Pneumonia is a common infection in people suffering with Alzheimer’s disease, leading to delirium, critical illness or severe neurological decline, which may be due to an amplified response of the blood-brain barrier (BBB) to peripheral insult. We assess the response of the BBB to repeated Streptococcus pneumoniae lung infection in rat model of Alzheimer’s disease (TgF344-AD), at 13- and 18-months old, using dynamic contrast-enhanced (DCE) MRI and filter exchange imaging. Higher BBB water exchange rate is initially detected in infected TgF344-AD rats. BBB water exchange rates correlated with hippocampus aquaporin-4 water channel expression in infected animals. We detected no differences in BBB permeability to gadolinium contrast agent measured by DCE-MRI, confirmed by staining for tight junction proteins, occludin and claudin-5. These findings provide insight into the mechanisms of how peripheral inflammation impacts the BBB.

AB - Pneumonia is a common infection in people suffering with Alzheimer’s disease, leading to delirium, critical illness or severe neurological decline, which may be due to an amplified response of the blood-brain barrier (BBB) to peripheral insult. We assess the response of the BBB to repeated Streptococcus pneumoniae lung infection in rat model of Alzheimer’s disease (TgF344-AD), at 13- and 18-months old, using dynamic contrast-enhanced (DCE) MRI and filter exchange imaging. Higher BBB water exchange rate is initially detected in infected TgF344-AD rats. BBB water exchange rates correlated with hippocampus aquaporin-4 water channel expression in infected animals. We detected no differences in BBB permeability to gadolinium contrast agent measured by DCE-MRI, confirmed by staining for tight junction proteins, occludin and claudin-5. These findings provide insight into the mechanisms of how peripheral inflammation impacts the BBB.

KW - Alzheimer’s disease

KW - Aquaporin-4

KW - Blood-brain barrier

KW - Lung infection

KW - Neuroinflammation

KW - Water-exchange MRI

M3 - Article

SN - 2948-197X

JO - npj Imaging

JF - npj Imaging

ER -

MRI detects blood-brain barrier alterations in a rat model of Alzheimer’s disease and lung infection

Abstract

Keywords

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