Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils

Context: The interruption of cerebral blood circulation may cause stroke characterized by high neurological deficits (NDs) as a result of neuronal dysfunction or destruction. Heparin may exert a neuroprotective effect against cerebral ischaemia/reperfusion injury. Objective: The objective of this st...

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Autores principales:	QingShan Ye, KeRong Hai, WenXun Liu, Yun Wang, XiaoHong Zhou, ZhenHai Ye, Xin Liu
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2019
Materias:	anticoagulation apoptosis histopathological damage Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/df7329a260b34bf2879a8a00e7ae1966
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spelling	oai:doaj.org-article:df7329a260b34bf2879a8a00e7ae19662021-11-17T14:21:56ZInvestigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils1388-02091744-511610.1080/13880209.2019.1648524https://doaj.org/article/df7329a260b34bf2879a8a00e7ae19662019-01-01T00:00:00Zhttp://dx.doi.org/10.1080/13880209.2019.1648524https://doaj.org/toc/1388-0209https://doaj.org/toc/1744-5116Context: The interruption of cerebral blood circulation may cause stroke characterized by high neurological deficits (NDs) as a result of neuronal dysfunction or destruction. Heparin may exert a neuroprotective effect against cerebral ischaemia/reperfusion injury. Objective: The objective of this study was to investigate the mechanism underlying the effects of heparin pre-treatment on cerebral injury in the gerbil. Materials and methods: A total of 80 healthy Mongolian gerbils were randomly divided into four groups to establish cerebral ischaemia model by bilateral carotid artery occlusion: control (no anaesthesia and surgery), sham (no occlusion), non-anticoagulation (occlusion), and anti-coagulation treatment groups (50 IU/100 g heparin pre-treated, occlusion). Gerbils were anesthetized with 40 mg/kg pentobarbital sodium through intraperitoneal injection before operation except for the control group. Then, the ND and histopathological damage (HD) scores were determined. The percentage of tumour necrosis factor (TNF)-α- and interleukin (IL)-1β-positive cells were calculated based on immunohistochemical results. The mRNA and protein levels of caspase-9, caspase-8, FasL, and calpain were evaluated with real-time polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Compared with non-anticoagulation group, heparin pre-treatment (50 IU/100 g) delayed the onset of dyspnoea (p < 0.05), and showed a significant decrease in ND (p < 0.01), mortality rate (p < 0.05), HD (p < 0.01) and percentage of positive cells for TNF-α, IL-1β (p < 0.01) in cerebral ischaemia gerbils. Besides, the expression levels of caspase-9, caspase-8, FasL, and calpain were reduced after pre-treatment with 50 IU/100 g heparin. Discussion and conclusions: The damage caused to gerbil brain was reduced upon pre-treatment with heparin, possibly through the amelioration of neuronal cell apoptosis and expression of TNF-α and IL-1β. These findings are expected to provide a new breakthrough in the study and treatment of cerebral ischaemia.QingShan YeKeRong HaiWenXun LiuYun WangXiaoHong ZhouZhenHai YeXin LiuTaylor & Francis Grouparticleanticoagulationapoptosishistopathological damageTherapeutics. PharmacologyRM1-950ENPharmaceutical Biology, Vol 57, Iss 1, Pp 519-528 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	anticoagulation apoptosis histopathological damage Therapeutics. Pharmacology RM1-950
spellingShingle	anticoagulation apoptosis histopathological damage Therapeutics. Pharmacology RM1-950 QingShan Ye KeRong Hai WenXun Liu Yun Wang XiaoHong Zhou ZhenHai Ye Xin Liu Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
description	Context: The interruption of cerebral blood circulation may cause stroke characterized by high neurological deficits (NDs) as a result of neuronal dysfunction or destruction. Heparin may exert a neuroprotective effect against cerebral ischaemia/reperfusion injury. Objective: The objective of this study was to investigate the mechanism underlying the effects of heparin pre-treatment on cerebral injury in the gerbil. Materials and methods: A total of 80 healthy Mongolian gerbils were randomly divided into four groups to establish cerebral ischaemia model by bilateral carotid artery occlusion: control (no anaesthesia and surgery), sham (no occlusion), non-anticoagulation (occlusion), and anti-coagulation treatment groups (50 IU/100 g heparin pre-treated, occlusion). Gerbils were anesthetized with 40 mg/kg pentobarbital sodium through intraperitoneal injection before operation except for the control group. Then, the ND and histopathological damage (HD) scores were determined. The percentage of tumour necrosis factor (TNF)-α- and interleukin (IL)-1β-positive cells were calculated based on immunohistochemical results. The mRNA and protein levels of caspase-9, caspase-8, FasL, and calpain were evaluated with real-time polymerase chain reaction (RT-PCR) and western blotting, respectively. Results: Compared with non-anticoagulation group, heparin pre-treatment (50 IU/100 g) delayed the onset of dyspnoea (p < 0.05), and showed a significant decrease in ND (p < 0.01), mortality rate (p < 0.05), HD (p < 0.01) and percentage of positive cells for TNF-α, IL-1β (p < 0.01) in cerebral ischaemia gerbils. Besides, the expression levels of caspase-9, caspase-8, FasL, and calpain were reduced after pre-treatment with 50 IU/100 g heparin. Discussion and conclusions: The damage caused to gerbil brain was reduced upon pre-treatment with heparin, possibly through the amelioration of neuronal cell apoptosis and expression of TNF-α and IL-1β. These findings are expected to provide a new breakthrough in the study and treatment of cerebral ischaemia.
format	article
author	QingShan Ye KeRong Hai WenXun Liu Yun Wang XiaoHong Zhou ZhenHai Ye Xin Liu
author_facet	QingShan Ye KeRong Hai WenXun Liu Yun Wang XiaoHong Zhou ZhenHai Ye Xin Liu
author_sort	QingShan Ye
title	Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
title_short	Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
title_full	Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
title_fullStr	Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
title_full_unstemmed	Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
title_sort	investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils
publisher	Taylor & Francis Group
publishDate	2019
url	https://doaj.org/article/df7329a260b34bf2879a8a00e7ae1966
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Investigation of the protective effect of heparin pre-treatment on cerebral ischaemia in gerbils

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