TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion

Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion in...
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Autor*in:	Bo Chen [verfasserIn] Shunhui Wei [verfasserIn] See Wee Low [verfasserIn] Charlene Priscilla Poore [verfasserIn] Andy Thiam-Huat Lee [verfasserIn] Bernd Nilius [verfasserIn] Ping Liao [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	transient receptor potential channels antibody reperfusion injury middle cerebral artery occlusion model vascular

Übergeordnetes Werk:	In: Biomedicines - MDPI AG, 2014, 11(2023), 5, p 1480
Übergeordnetes Werk:	volume:11 ; year:2023 ; number:5, p 1480

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc

DOI / URN:	10.3390/biomedicines11051480

Katalog-ID:	DOAJ09441324X

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520			\|a Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management.
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allfieldsSound	10.3390/biomedicines11051480 doi (DE-627)DOAJ09441324X (DE-599)DOAJ8e4a42b0dd034554b1f8e22bf77dcef2 DE-627 ger DE-627 rakwb eng QH301-705.5 Bo Chen verfasserin aut TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management. transient receptor potential channels antibody reperfusion injury middle cerebral artery occlusion model vascular Biology (General) Shunhui Wei verfasserin aut See Wee Low verfasserin aut Charlene Priscilla Poore verfasserin aut Andy Thiam-Huat Lee verfasserin aut Bernd Nilius verfasserin aut Ping Liao verfasserin aut In Biomedicines MDPI AG, 2014 11(2023), 5, p 1480 (DE-627)750370483 (DE-600)2720867-9 22279059 nnns volume:11 year:2023 number:5, p 1480 https://doi.org/10.3390/biomedicines11051480 kostenfrei https://doaj.org/article/8e4a42b0dd034554b1f8e22bf77dcef2 kostenfrei https://www.mdpi.com/2227-9059/11/5/1480 kostenfrei https://doaj.org/toc/2227-9059 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 11 2023 5, p 1480
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callnumber-first	Q - Science
author	Bo Chen
spellingShingle	Bo Chen misc QH301-705.5 misc transient receptor potential channels misc antibody misc reperfusion injury misc middle cerebral artery occlusion misc model misc vascular misc Biology (General) TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion
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topic_title	QH301-705.5 TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion transient receptor potential channels antibody reperfusion injury middle cerebral artery occlusion model vascular
topic	misc QH301-705.5 misc transient receptor potential channels misc antibody misc reperfusion injury misc middle cerebral artery occlusion misc model misc vascular misc Biology (General)
topic_unstemmed	misc QH301-705.5 misc transient receptor potential channels misc antibody misc reperfusion injury misc middle cerebral artery occlusion misc model misc vascular misc Biology (General)
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title	TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion
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title_full	TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion
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author_browse	Bo Chen Shunhui Wei See Wee Low Charlene Priscilla Poore Andy Thiam-Huat Lee Bernd Nilius Ping Liao
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title_sort	trpm4 blocking antibody protects cerebral vasculature in delayed stroke reperfusion
callnumber	QH301-705.5
title_auth	TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion
abstract	Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management.
abstractGer	Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management.
abstract_unstemmed	Reperfusion therapy for acute ischemic stroke aims to restore the blood flow of occluded blood vessels. However, successful recanalization is often associated with disruption of the blood-brain barrier, leading to reperfusion injury. Delayed recanalization increases the risk of severe reperfusion injury, including severe cerebral edema and hemorrhagic transformation. The TRPM4-blocking antibody M4P has been shown to alleviate reperfusion injury and improve functional outcomes in animal models of early stroke reperfusion. In this study, we examined the role of M4P in a clinically relevant rat model of delayed stroke reperfusion in which the left middle cerebral artery was occluded for 7 h. To mimic the clinical scenario, M4P or control IgG was administered 1 h before recanalization. Immunostaining showed that M4P treatment improved vascular morphology after stroke. Evans blue extravasation demonstrated attenuated vascular leakage following M4P treatment. With better vascular integrity, cerebral perfusion was improved, leading to a reduction of infarct volume and animal mortality rate. Functional outcome was evaluated by the Rotarod test. As more animals with severe injuries died during the test in the control IgG group, we observed no difference in functional outcomes in the surviving animals. In conclusion, we identified the potential of TRPM4 blocking antibody M4P to ameliorate vascular injury during delayed stroke reperfusion. If combined with reperfusion therapy, M4P has the potential to improve current stroke management.
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title_short	TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion
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author2	Shunhui Wei See Wee Low Charlene Priscilla Poore Andy Thiam-Huat Lee Bernd Nilius Ping Liao
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up_date	2024-07-03T23:01:15.914Z
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TRPM4 Blocking Antibody Protects Cerebral Vasculature in Delayed Stroke Reperfusion

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