Recombinant soluble form of receptor for advanced glycation end products ameliorates microcirculation impairment and neuroinflammation after subarachnoid hemorrhage.
Journal
Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
Series/Report No.
Neurotherapeutics
Journal Volume
21
Journal Issue
2
Start Page
e00312
ISSN
1878-7479
Date Issued
2024-03
Author(s)
Yang, Ling-Yu
Tang, Sung-Chun
Lee, Jing-Er
Chen, Yong-Ren
Chen, Yi-Tzu
DOI
10.1016/j.neurot.2023.e00312
Abstract
Impaired cerebral microcirculation after subarachnoid hemorrhage (SAH) has been shown to be related to delayed ischemic neurological deficits (DIND). We previously demonstrated the involvement of the receptor for advanced glycation end products (RAGE) in the pathogenesis of SAH related neuronal death. In the present study, we aimed to investigate the therapeutic effects of a recombinant soluble form of RAGE (sRAGE) on microcirculation impairment following SAH. Intrathecal injection of autologous blood in rats, mixed primary astrocyte and microglia cultures exposed to hemolysates and endothelial cells (ECs) from human brain microvascular exposed to glia-conditioned medium or SAH patient's CSF were used as experimental SAH models in vivo and in vitro. The results indicated that intrathecal administration of recombinant sRAGE significantly ameliorated the vasoconstriction of cortical arterioles and associated perfusion impairment, brain edema, reduced cell death, endothelial dysfunction, and improved motor performance at 24 and 48 h after SAH induction in rats. The in vitro results further showed that recombinant sRAGE significantly reduced astrocyte swelling and microglia activation, in parallel with decreased mRNA expression levels of pro-inflammatory cytokines including interleukin-6 (IL-6) and interleukin-1β (IL-1β) in vitro. Moreover, the in vitro model of SAH-induced p-eNOS and eNOS suppression, along with stress fiber formation in brain microvascular ECs, was effectively reversed by sRAGE treatment and led to a decrease in cleaved-caspase 3 expression. In summary, recombinant sRAGE effectively lessened microcirculation impairment and vascular injury after SAH via the mechanism of anti-inflammation, which may provide a potential therapeutic strategy for SAH.
Subjects
Aneurysmal subarachnoid hemorrhage
Brain edema
Endothelial dysfunction
Microcirculation impairment
Neuroinflammation
Soluble form of receptor for advanced glycation end products (sRAGE)
SDGs
Publisher
Elsevier B.V.
Type
journal article