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The MEK Inhibitor T...
The MEK Inhibitor Trametinib Improves Outcomes following Subarachnoid Haemorrhage in Female Rats
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- Bömers, Jesper Peter (författare)
- Copenhagen University Hospital
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- Grell, Anne Sofie (författare)
- Copenhagen University Hospital
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- Edvinsson, Lars (författare)
- Lund University,Lunds universitet,Experimentell kärlforskning,Forskargrupper vid Lunds universitet,LTH profilområde: Avancerade ljuskällor,LTH profilområden,Lunds Tekniska Högskola,Experimental Vascular Research,Lund University Research Groups,LTH Profile Area: Photon Science and Technology,LTH Profile areas,Faculty of Engineering, LTH,Copenhagen University Hospital
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- Johansson, Sara Ellinor (författare)
- Copenhagen University Hospital
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- Haanes, Kristian Agmund (författare)
- Copenhagen University Hospital
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(creator_code:org_t)
- 2022-11-22
- 2022
- Engelska.
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Ingår i: Pharmaceuticals. - : MDPI AG. - 1424-8247. ; 15:12
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- cerebral artery
- ET-1
- rat
- SAH
- subarachnoid haemorrhage
- trametinib
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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