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Fixed arteriovenous malformation in the differential expression of leptin to its bleeding mechanism of angiogenesis-related genes in the human brain

Author: XieQing
Tutor: ChenXianCheng;GongZuo;GuYuXiang
School: Fudan University
Course: Surgery
Keywords: Cerebral arteriovenous malformations Angiogenesis Gene Chip Leptin Leptin receptor Signal transducer and activator of transcription 3 Cerebral hemorrhage Cerebral edema Heat shock protein Behavior
CLC: R743.4
Type: PhD thesis
Year: 2007
Downloads: 101
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Abstract


PARTⅠDIFFERENTIAL ANGIOGENESIS GENE EXPRESSION OF DIFFERENT PARTS IN HUMAN BRAIN ARTERIOVENOUS MALFORMATIONS BY FOCUSED DNA MICROARRAY ANALYSISAbstract Background and Purpose: A typical human brain arteriovenous malformation (BAVM) is composed of arterial, nidal and venous parts. There is active vascular remodeling in BAVM. We examined angiogenesis gene expression patterns at these different parts in BAVM by the focused DNA microarray technique. Methods: We analyzed arterial, nidal, venous and adjacent brain tissue from six resected BAVMs by quantifying mRNA expression levels on Oligo GEArray Human Angiogenesis Microarray OHS-024 (SuperArray, Inc., Frederick, MD). Adjacent brain tissue is as self control. Results: By comparison, 44 of 113 angiogenesis related key genes are found differential expressed. Our focus is mainly on nidus, but the results also showed distinct expression patterns of the other parts in BAVM. Conclusions: It’ s the first time to use focused DNA microarray technique to compare gene expressions at different parts of BAVM. Self-contrast is a promising way to focus special gene expression pattern of BAVM, so that it may help us to find the phenotype of hemorrhagic BAVM and develop new strategies on treating this disease.PARTⅡEXPRESSION AND EFFECT OF LEPTIN ON HUMAN BRAIN ARTERIOVENOUS MALFORMATIONSAbstract Background and Purpose: The common clinical manifestation of human brain arteriovenous malformation (BAVM) is intracerebral hemorrhage (ICH). The goal of modern therapy is to lessen the morbidity and mortality of ICH. But the mechanism of BAVM rupture to hemorrhage is still unclear. The goal is to investigate expression and effect of leptin on human BAVM. Methods: We analyzed transcription and translation level of leptin, leptin receptor and STAT3 by different methods, as gene chip, RT-PCR, realtime-PCR, immunohistochemistry and western blot. Results: Compared with brain tissue around BAVM, arterial and venous parts, leptin, leptin receptor and STAT3 expressed highly on nidus of BAVM. Conclusions: It suggests that leptin may play an important role in rupture to hemorrhage of BAVM. It opens a brand-new window on investigating the mechanism of BAVM hemorrhage and find new effect of leptin, which is mainly an endocrine on obesity.PARTⅢTHE ROLE OF LEPTIN IN EXPERIMENTAL INTRACEREBRAL HEMORRHAGE OF RATS: A PRELIMINARY STUDY ON ITS EARLY CHANGES AND EFFECTAbstract Background and Purpose: Leptin may play a role in occurrence and development of intracerebral hemorrhage. Since brain arteriovenous malformations usually rupture into intracranial hemorrhage, they are similar to the changes of rat model after experimental intracerebral hemorrhage which has been used at our study group for many years. Our goals are to exam early changes of leptin, leptin receptor and STAT3 after EICH, and typical time courses of other factors after EICH such as activity of thrombin, water content, behavioral test and levels of heat shock proteins. Methods: Male Sprague-Dawley rats received an intracerebral infusion of 100μL autologous blood or sham needle. Factors were tested as activity of thrombin, water content, behavioral test and levels of heat shock proteins by western blot. Realtime-PCR was used to test the early changes of leptin, leptin receptor and STAT3.Results: Activity of thrombin raised at 1 hour after EICH and maintained at high level at 24hr. Brain swelling was more severe at 3 days after ICH (P<0.05) . There were also more severe neurological deficits at 1 day after ICH, which persisted for the 2 weeks of monitoring (P<0.05) . The rats also had a change of perihematomal induction of HSP27 and HSP32 (P<0.05) by Western blot analysis. Leptin increased as 5 times as before EICH, while leptin receptor 1.5 times and STAT3 0.8 times. Conclusions: The results showed there might be relationships among changes of leptin, thrombin, heat shock protein and brain swelling after EICH. With the high expression of leptin in the ICH model of rat, it confirms that leptin may play an important role in bleeding and developing of BAVM after rupture.

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CLC: > Medicine, health > Neurology and psychiatry > Neurology > Cerebrovascular disease > Cerebral vascular malformations
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