Switching Off Vascular MAPK Signaling: A Novel Strategy to Prevent Delayed Cerebral Ischemia Following Subarachnoid Hemorrhage.

Autor: Edvinsson L; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Sölvegatan 19, 22100, Lund, Sweden. lars.edvinsson@med.lu.se.; Department of Experimental Research, Glostrup Research Institute, CopenhagenUniversity, Copenhagen, Denmark. lars.edvinsson@med.lu.se., Krause DN; Division of Experimental Vascular Research, Department of Clinical Sciences, Lund University, Sölvegatan 19, 22100, Lund, Sweden.; Department of Pharmaceutical Sciences, SchoolofPharmacy&PharmaceuticalSciences, University of California at Irvine, Irvine, CA, USA.
Jazyk: angličtina
Zdroj: Translational stroke research [Transl Stroke Res] 2024 Feb 09. Date of Electronic Publication: 2024 Feb 09.
DOI: 10.1007/s12975-024-01234-z
Abstrakt: Patients who initially survive the rupture and repair of a brain aneurysm often take a devastating turn for the worse some days later and die or suffer permanent neurologic deficits. This catastrophic sequela is attributed to a delayed phase of global cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH), but we lack effective treatment. Here we present our view, based on 20 years of research, that the initial drop in blood flow at the time of rupture triggers genomic responses throughout the brain vasculature that manifest days later as increased vasoconstriction and decreased cerebral blood flow. We propose a novel treatment strategy to prevent DCI by early inhibition of the vascular mitogen-activated protein kinase (MAPK) pathway that triggers expression of vasoconstrictor and inflammatory mediators. We summarize evidence from experimental SAH models showing early treatment with MAPK inhibitors "switches off" these detrimental responses, maintains flow, and improves neurological outcome. This promising therapy is currently being evaluated in clinical trials.
(© 2024. The Author(s).)
Databáze: MEDLINE
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