Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/147000
Title: Direct myosin-2 inhibition enhances cerebral perfusion resulting in functional improvement after ischemic stroke
Authors: Pénzes, Máté
Túrós, Demeter
Máthé, Domokos
Szigeti, Krisztián
Hegedűs, Nikolett
Rauscher, Anna Ágnes
Tóth, Péter
Ivic, Ivan
Padmanabhan, Parasuraman
Pál, Gabriella
Dobolyi, Árpád
Gyimesi, Máté
Málnási-Csizmadia, András
Keywords: Science::Medicine
Issue Date: 2020
Source: Pénzes, M., Túrós, D., Máthé, D., Szigeti, K., Hegedűs, N., Rauscher, A. Á., Tóth, P., Ivic, I., Padmanabhan, P., Pál, G., Dobolyi, Á., Gyimesi, M. & Málnási-Csizmadia, A. (2020). Direct myosin-2 inhibition enhances cerebral perfusion resulting in functional improvement after ischemic stroke. Theranostics, 10(12), 5341-5356. https://dx.doi.org/10.7150/thno.42077
Journal: Theranostics
Abstract: Acute ischemic stroke treatment faces an unresolved obstacle as capillary reperfusion remains insufficient after thrombolysis and thrombectomy causing neuronal damage and poor prognosis. Hypoxia-induced capillary constriction is mediated by actomyosin contraction in precapillary smooth muscle cells (SMCs) therefore smooth muscle myosin-2 could be an ideal target with potentially high impact on reperfusion of capillaries. Methods: The myosin-2 inhibitor para-aminoblebbistatin (AmBleb) was tested on isolated human and rat arterioles to assess the effect of AmBleb on vasodilatation. Transient middle cerebral artery occlusion (MCAO) was performed on 38 male Wistar rats followed by local administration of AmBleb into the ischemic brain area. Development of brain edema and changes in cerebrovascular blood flow were assessed using MRI and SPECT. We also tested the neurological deficit scores and locomotor asymmetry of the animals for 3 weeks after the MCAO operation. Results: Our results demonstrate that AmBleb could achieve full relaxation of isolated cerebral arterioles. In living animals AmBleb recovered cerebral blood flow in 32 out of the 65 affected functional brain areas in MCAO operated rats, whereas only 8 out of the 67 affected areas were recovered in the control animals. Animals treated with AmBleb also showed significantly improved general and focal deficit scores in neurological functional tests and showed significantly ameliorated locomotor asymmetry. Conclusion: Direct inhibition of smooth muscle myosin by AmBleb in pre-capillary SMCs significantly contribute to the improvement of cerebral blood reperfusion and brain functions suggesting that smooth muscle myosin inhibition may have promising potential in stroke therapies as a follow-up treatment of physical or chemical removal of the occluding thrombus.
URI: https://hdl.handle.net/10356/147000
ISSN: 1838-7640
DOI: 10.7150/thno.42077
Rights: © 2020 The Author(s). All rights reserved. This paper was published in Theranostics and is made available with permission of The Author(s).
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

Files in This Item:
File Description SizeFormat 
thnov10p5341.pdf2.9 MBAdobe PDFView/Open

Page view(s)

103
Updated on Jun 26, 2022

Download(s)

9
Updated on Jun 26, 2022

Google ScholarTM

Check

Altmetric


Plumx

Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.