Effect of advanced maternal age on ischemic stroke vulnerability in aged rats: Investigating on blood-brain barrier permeability and gene expression

Abstract

Background: Advanced maternal age (AMA), commonly defined as pregnancy at or above 35 years old. Based on the evidence, this trend has raised concerns about potential health consequences for mothers, particularly in relation to ischemic stroke. Studies suggest that AMA may be associated with a higher risk of ischemic stroke in women due to physiological changes that impact vascular health and increase cardiovascular risk factors. The aim of this study was to investigate the effect of AMA on the extent of damage after ischemic stroke in aged rats.

Methods: Female rats that gave birth at an old age (10 months) and at a young age (4 months) were subjected to ischemic stroke in old age (20 months) and subsequently compared.We assessed neurological deficits, infarct volume, blood-brain barrier (BBB) permeability, TNF-alpha levels, total oxidant capacity, and gene expressions that play a role in BBB integrity (VEGF, Occludin, and MMP-9) following ischemic stroke.

Results: There were significantly elevated levels of MMP-9 expression and reduced levels of occludin in AMA rats. Additionally, AMA rats had significantly higher levels of TNF-alpha and total oxidant capacity after experiencing an ischemic stroke. AMA rats showed significantly higher brain water content (BBB permeability), infarct volume, and neurological deficits compared to young-aged pregnancies.

Discussion: Complex relationship between pregnancy-related physiological changes, aging, vascular gene expression, and inflammatory factors may play a role in the increased vulnerability observed in older pregnant rats. The similarities between pregnancy-related alterations and aging highlight the influence of advanced maternal age on susceptibility to ischemic stroke.

Keywords: Advanced maternal age; Aging; MMP9; Occluding; Stroke; VEGF.

Fig. 1

Experimental design overview.

Fig. 2

Displays the (a-b) infarct volume (n = 5 rats/group), (c) brain Evans blue content (n = 4 rats/group) and (d) scores for neurological deficits (n = 14–16 rats/group) in the SHAM, ISO, YPS, and AMAPS groups. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 3

Depicts the mRNA expression levels of (a) VEGF (n = 5–6 rats/group), (b) Occludin (n = 5–6 rats/group), and (c) MMP9 (n = 5–6 rats/group) in the brain ischemic tissue across the SHAM, ISO, YPS, and AMAPS groups.

Fig. 4

Presents the levels of TNF-α (n = 5–6 rats/group) and TOC (n = 5–6 rats/group) in ischemic tissue across the SHAM, ISO, YPS, and AMAPS groups.