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The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats.

Authors :
Bömers, Jesper Peter
Grell, Anne-Sofie
Edvinsson, Lars
Johansson, Sara Ellinor
Haanes, Kristian Agmund
Source :
Pharmaceuticals (14248247). Dec2022, Vol. 15 Issue 12, p1446. 15p.
Publication Year :
2022

Abstract

Aneurysmal subarachnoid haemorrhage (SAH) is a haemorrhagic stroke that causes approximately 5% of all stroke incidents. We have been working on a treatment strategy that targets changes in cerebrovascular contractile receptors, by blocking the MEK/ERK1/2 signalling pathway. Recently, a positive effect of trametinib was found in male rats, but investigations of both sexes in pre-clinical studies are an important necessity. In the current study, a SAH was induced in female rats, by autologous blood-injection into the pre-chiasmatic cistern. This produces a dramatic, transient increase in intracranial pressure (ICP) and an acute and prolonged decrease in cerebral blood flow. Rats were then treated with either vehicle or three doses of 0.5 mg/kg trametinib (specific MEK/ERK1/2 inhibitor) intraperitoneally at 3, 9, and 24 h after the SAH. The outcome was assessed by a panel of tests, including intracranial pressure (ICP), sensorimotor tests, a neurological outcome score, and myography. We observed a significant difference in arterial contractility and a reduction in subacute increases in ICP when the rats were treated with trametinib. The sensory motor and neurological outcomes in trametinib-treated rats were significantly improved, suggesting that the improved outcome in females is similar to that of males treated with trametinib. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
14248247
Volume :
15
Issue :
12
Database :
Academic Search Index
Journal :
Pharmaceuticals (14248247)
Publication Type :
Academic Journal
Accession number :
161038376
Full Text :
https://doi.org/10.3390/ph15121446