Prostaglandin E1-Mediated Collateral Recruitment Is Delayed in a Neonatal Rat Stroke Model

Abstract

While arterial reflow after a stroke represents an important challenge for better outcomes, it is also very important that sudden recanalization does not produce local oxidative and nitrogen species, deleterious for the brain and more particularly the immature brain. Our objective was to determine whether a supply in prostaglandin (Pg) E1 (Alprostadil), via its action on arterial pressure, might progressively improve cerebral reperfusion in a neonatal stroke model. Arterial blood flow was measured using ultrasonography. Rate-limiting and Pg terminal synthesizing enzymes were evaluated using reverse-transcriptase polymerase chain reaction. Our data suggests that a supply in PgE1 might delay and improve the ipsilateral reperfusion by decreasing thromboxane A synthase-1 gene, the density of reactive astrocytes and lesion volume.

Prostaglandin E1 Alleviates Cognitive Dysfunction in Chronic Cerebral Hypoperfusion Rats by Improving Hemodynamics

“…Currently, the underlying mechanism remains unknown. Since it has been reported that PGE1 might improve ipsilateral reperfusion and decrease the number of reactive astrocytes and lesion volume in neonatal stroke model rats (Bonnin et al, 2018), we speculate that PGE1-mediated CBF enhancement may contribute to the reduction in astrocyte activation, which in turn may reduce inflammatory responses and alleviate cognitive impairment. In addition, it has been reported that endoplasmic reticulum stress plays critical roles in determining the degree of astroglial activation after brain ischemia (Yoshikawa et al, 2015).…”

Collateral Supply in Preclinical Cerebral Stroke Models

“…No increase was observed in the adult rats at this time point. Data provided for neonatal stroke from references [9,16,32,33], and for adult stroke from [55] depending of early reinforcement of the collateral supply from tissue that is already infarcted, thus the inner and outer boundaries of ischemic penumbra. Cortical collateral circulation has been scored with CT angiography that allows for temporal discrimination between patients with poor from those with good collateral recruitment [68].…”

“…No increase was observed in the adult rats at this time point. Data provided for neonatal stroke from references [ 9 , 16 , 32 , 33 ], and for adult stroke from [ 55 ] …”

“…By contrast, in the same model, Alprostadil® (PgE1, 20 µg/kg administered i.p., with 4 injections every 5 min) No effect on lesion [40] enhanced collateral supply 1 h after reperfusion for the left ICA (supplying the left hemisphere) only. This collateral supply is unlikely to correspond to a steal phenomenon, although the necessary measurements were not made to confirm this, as PgE1 treatment also reduced thromboxane A-synthase-1 gene expression 2 h after treatment, and reactive astrocyte density and lesion volume after 48 h of recovery [33]. Ultrasound measurements were taken at only one time point (1 h after CCAo release).…”

Leptomeningeal anastomoses: Mechanisms of pial collateral remodeling in ischemic stroke

“…Treatment with prostaglandin E1 in neonatal rats showed improvements in blood flow back to basal levels and significant reductions in lesion volume 2 days following injury in treated mice. The restoration in blood flow was thought to be due to increases in recruitment and blood flow through primary collaterals in the circle of Willis or through pial collaterals, although no direct analysis of the collateral vessels was performed (Bonnin et al, 2018). While this work sets the stage to solidify prostaglandin E1 as a potential therapy for stroke aimed at improving collateral vasodilation, more direct studies of LMAs are necessary.…”