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Advanced Neurology

REVIEW ARTICLE
Implications of age-related changes in the

blood-brain barrier for ischemic stroke and new
treatment strategies

Sarah Eide, Zhong-Ping Feng*

Department of Physiology, University of Toronto, 3308 Medical Sciences Building, 1 King’s College
Circle, Toronto, Ontario, Canada M5G 1A8

Abstract

Ischemic strokes are prevalent across all age groups. Recent research has highlighted
the importance of better understanding ischemia-induced damage of the blood-
brain barrier (BBB) because it is related to both the severity of ischemic injury and
neurological outcomes. The influence of advancing age on the structure and function
of the BBB and the potential influence of these changes on ischemic stroke injury
have received little consideration to date. Therefore, the present review outlines how
ischemic injury influences the structure and function of the BBB at the anatomical,
cellular, and molecular levels, and how these changes differ between adult and
elderly populations with and without age-related comorbid diseases. This review
further discusses how age-dependent changes and features of the BBB, and the
corresponding alterations in response to ischemia, can affect the efficacy and delivery
of current and future treatment options. Current research efforts are underway to
develop prospective stroke treatment strategies that target the restoration of BBB
*Corresponding author: functionality. This review also discusses the importance of considering the unique
Zhong-Ping Feng properties and characteristics of the BBB in elderly individuals for developing new
(zp.feng@utoronto.ca) stroke treatment strategies.
Citation: Eide S, Feng ZP, 2022,
Implications of age-related changes
in the blood-brain barrier for Keywords: Ischemic stroke; Blood-brain barrier; Inflammation; Drug delivery; Diabetes;
ischemic stroke and new treatment Alzheimer’s disease
strategies. Adv Neuro, 1(2): 1
https://doi.org/10.36922/an.v1i2.1
Received: December 13, 2021
Accepted: May 13, 2022 1. Introduction
Published Online: August 12, 2022 Ischemic strokes can occur at any point in life, independent of age. Nevertheless,
the blood-brain barrier (BBB) changes with age , and changes in BBB integrity and
[1]
Copyright: © 2022 Author(s).
This is an Open Access article functionality may significantly affect the brain. With a growing line of evidence focusing
distributed under the terms of the on the effect of BBB integrity on ischemic injury and recovery [2-4] , it is of increasing
Creative Commons Attribution importance that age-dependent characteristics of the BBB be considered. In a healthy
License, permitting distribution,
and reproduction in any medium, state, the BBB acts as a physical and enzymatic barrier that protects the neuronal
provided the original work is environment from blood-borne toxins, inflammation, and potential fluctuations in ion
properly cited. and water homeostasis to maintain neuronal health and activity . This is accomplished
[5]
Publisher’s Note: AccScience by a single-cell layer of specialized endothelial cells connected together through tight
Publishing remains neutral with junctional complexes made of occludin, zona occludens (ZO), and claudin proteins. This
regard to jurisdictional claims in
published maps and institutional microvascular barrier of the brain limits paracellular and transcellular movement from
affiliations. the blood into the brain .
[5]

Volume 1 Issue 2 (2022) 1 https://doi.org/10.36922/an.v1i2.1