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Neurotransmitter regulation of extracellular signal-regulated kinase expression following subarachnoid hemorrhage 被引量:2

Neurotransmitter regulation of extracellular signal-regulated kinase expression following subarachnoid hemorrhage
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摘要 BACKGROUND: Very few studies have addressed neuronal injury in cerebral vasospasm and subarachnoid hemorrhage (SAH), and the role of neurotransmitters in the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) expression following SAH. OBJECTIVE: To analyze neurotransmitter regulation of ERK1/2 expression through the use of signal transduction, and to investigate cerebral injury mechanisms following SAH. DESIGN, TIME AND SETTING: A completely randomized grouping and controlled animal experiment was performed at the Experimental Center of Medical College of Xi'an Jiaotong University from March to December 2008. MATERIALS: Extraceliular signal-regulated ERK1/2 polyclonal antibody and streptavidin-peroxidase method kits were purchased from Beijing Biosynthesis Biotechnology, China; DAB kit was purchased from Zhongshan Golden Bridge Biotechnology, China; TUNEL kit was purchased from Promega, USA. METHODS: A total of 114 male, Sprague Dawley rats, aged 55-63 days old, were randomly assigned to five groups: SAH (n = 30), saline control (n = 30), puncture control (n = 30), normal control (n = 6), and neurotransmitter-treated (n = 18). The SAH model was established by twice injecting blood through the cisterna magna. The neurotransmitters-treated group was subdivided into three groups according to drugs injected into the lateral cerebral ventricle: acetylcholine chloride, norepinephrine, and saline, with six animals in each group. MAIN OUTCOME MEASURES: Rats from the SAH, saline control, and puncture control groups were respectively sacrificed at 6, 12, and 24 hours, as well as 3 and 5 days, with six rats at each time point. The normal control group rats were sacrificed at 6 hours, and the neurotransmitter group rats were sacrificed 3 days following neurotransmitter injection. Morphological cellular changes were observed by hematoxylin and eosin staining. Immunohistochemical SP method was used to detect expression of ERK1/2 in the cortex, and cortical apoptosis was detected using the TUNEL method. RESULTS: Neural tissue edema, apoptosis, and necrosis occurred in the cortex of the SAH group. ERK1/2-positive cells were first observed at 6 hours, peaked at 12 hours following SAH in the cortex, and gradually decreased thereafter. Cellular apoptosis was observed in the cortex at 6 hours and peaked at 24 hours following SAH. ERK1/2 distribution in the brain overlapped apoptotic cells to a great degree. The number of ERK1/2-positive and apoptotic cells was significantly greater in the SAH group compared with the three control groups (P 〈 0.05). Compared to the number of ERK1/2-positive cells in the saline-treated group, acetylcholine chloride treatment resulted in decreased ERK1/2 expression and apoptosis (P 〈 0.05). Norepinephrine resulted in increased ERK1/2 expression, but there was no significance in apoptosis compared to the saline-treated group (P 〉 0.05). CONCLUSION: Apoptosis was observed early in the rat cortex following SAH. In addition, ERK1/2 was expressed earlier than apoptosis. Acetylcholine chloride treatment resulted in decreased numbers of apoptotic cells following SAH, possibly by down-regulating ERK1/2 expression. BACKGROUND: Very few studies have addressed neuronal injury in cerebral vasospasm and subarachnoid hemorrhage (SAH), and the role of neurotransmitters in the regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) expression following SAH. OBJECTIVE: To analyze neurotransmitter regulation of ERK1/2 expression through the use of signal transduction, and to investigate cerebral injury mechanisms following SAH. DESIGN, TIME AND SETTING: A completely randomized grouping and controlled animal experiment was performed at the Experimental Center of Medical College of Xi'an Jiaotong University from March to December 2008. MATERIALS: Extraceliular signal-regulated ERK1/2 polyclonal antibody and streptavidin-peroxidase method kits were purchased from Beijing Biosynthesis Biotechnology, China; DAB kit was purchased from Zhongshan Golden Bridge Biotechnology, China; TUNEL kit was purchased from Promega, USA. METHODS: A total of 114 male, Sprague Dawley rats, aged 55-63 days old, were randomly assigned to five groups: SAH (n = 30), saline control (n = 30), puncture control (n = 30), normal control (n = 6), and neurotransmitter-treated (n = 18). The SAH model was established by twice injecting blood through the cisterna magna. The neurotransmitters-treated group was subdivided into three groups according to drugs injected into the lateral cerebral ventricle: acetylcholine chloride, norepinephrine, and saline, with six animals in each group. MAIN OUTCOME MEASURES: Rats from the SAH, saline control, and puncture control groups were respectively sacrificed at 6, 12, and 24 hours, as well as 3 and 5 days, with six rats at each time point. The normal control group rats were sacrificed at 6 hours, and the neurotransmitter group rats were sacrificed 3 days following neurotransmitter injection. Morphological cellular changes were observed by hematoxylin and eosin staining. Immunohistochemical SP method was used to detect expression of ERK1/2 in the cortex, and cortical apoptosis was detected using the TUNEL method. RESULTS: Neural tissue edema, apoptosis, and necrosis occurred in the cortex of the SAH group. ERK1/2-positive cells were first observed at 6 hours, peaked at 12 hours following SAH in the cortex, and gradually decreased thereafter. Cellular apoptosis was observed in the cortex at 6 hours and peaked at 24 hours following SAH. ERK1/2 distribution in the brain overlapped apoptotic cells to a great degree. The number of ERK1/2-positive and apoptotic cells was significantly greater in the SAH group compared with the three control groups (P 〈 0.05). Compared to the number of ERK1/2-positive cells in the saline-treated group, acetylcholine chloride treatment resulted in decreased ERK1/2 expression and apoptosis (P 〈 0.05). Norepinephrine resulted in increased ERK1/2 expression, but there was no significance in apoptosis compared to the saline-treated group (P 〉 0.05). CONCLUSION: Apoptosis was observed early in the rat cortex following SAH. In addition, ERK1/2 was expressed earlier than apoptosis. Acetylcholine chloride treatment resulted in decreased numbers of apoptotic cells following SAH, possibly by down-regulating ERK1/2 expression.
出处 《Neural Regeneration Research》 SCIE CAS CSCD 2010年第3期214-220,共7页 中国神经再生研究(英文版)
基金 the National Natural Science Foundation of China, No. 30870844 the National High Technology Research and Development Program of China (863 Program), No. 2006AA02Z4Z4 the New Century Excellent Talents in University, Ministry of Education, No. NECT-05-0831
关键词 extracellular signal-regulated kinase subarachnoid hemorrhage APOPTOSIS NEUROTRANSMITTERS brain injury neural regeneration extracellular signal-regulated kinase subarachnoid hemorrhage apoptosis neurotransmitters brain injury neural regeneration
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