权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neuroprotective Actions of hCG in a Mouse Model of Term and Preterm Brain Injury

hCG 在足月和早产脑损伤小鼠模型中的神经保护作用

基本信息

批准号：
10404106
负责人：
Rafael Galindo
金额：
$ 34.45万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10404106
关键词：
Address Animals Anti-Inflammatory Agents Asphyxia Neonatorum Behavioral Biochemical Biological Blood - brain barrier anatomy Brain Brain Hypoxia-Ischemia Brain Injuries Cerebral Ischemia-Hypoxia Cerebrum Chorionic Gonadotropin Chronic Cognitive Cyclic AMP-Dependent Protein Kinases Data Dependence Development Developmental Disabilities Differentiation and Growth Disease Dose Drug Kinetics Electroencephalography Encephalitis Evaluation Exposure to Fetus Functional disorder Genes Glutamate Receptor Growth Health Hippocampus (Brain)Histologic Hormones Human Human Chorionic Gonadotropin In Vitro Infant Injections Injury Knockout Mice LH Receptors LIF gene Life Lipopolysaccharides Luteinizing Hormone MEKs Measures Mediating Methods Modeling Molecular Morbidity - disease rate Mus Neonatal Neonatal Brain Injury Nerve Degeneration Nervous System Physiology Nervous system structure Neurologic Neurologic Effect Neuronal Injury Neurons Neuroprotective Agents Newborn Infant Pathway interactions Peripheral Pharmacology Phosphotransferases Pregnancy Preterm brain injury Prevention Process Property Proteins Receptor Activation Research Rice Role Safety Seizures Signal Pathway Term Birth Testing Therapeutic Agents Time Vascular Endothelial Growth Factors cerebral degeneration clinically significant disability excitotoxicity exposed human population fetal improved in vivo inhibitor injured innovation intraperitoneal knock-down mouse model neonatal hypoxic-ischemic brain injury neonatal mice neonate neurobehavioral neurobiological mechanism neuronal survival neurophysiology neuroprotection neurotrophic factor newborn brain injury novel novel therapeutics premature preterm newborn pup receptor receptor function small hairpin RNA systemic inflammatory response tissue injury translational impact treatment strategy

项目摘要

ABSTRACT Brain injury from neonatal hypoxia-ischemia (HI) in the term and preterm newborn often results in chronic neurological and developmental disability and yet, only limited therapies are available for its prevention and treatment. Human chorionic gonadotropin (hCG) is a placentally derived hormone with biological properties that make it suitable for its use in neuroprotection of the injured newborn brain. hCG structurally and functionally acts as an immunomodulating neurotrophin protein, enhancing the survival, growth and differentiation of immature neurons. Furthermore, hCG receptors are found in the fetal nervous system and hCG itself can cross the blood brain barrier and enter the brain. We also find that peripheral intraperitoneal administration of this hormone protects the newborn mouse brain against the effect of HI. Furthermore, direct exposure of hCG to immature injured neurons increases their survival and growth and protects them against glutamate receptor-mediated excitotoxicity. However, little is known about hCG’s maximal neuroprotective efficacy, safety and the cellular mechanisms responsible its anti-degenerative effects. Furthermore, the function of brain hCG receptors in the healthy and diseased developing brain remains unknown. To address this concern, we propose to use biochemical, molecular, histological, behavioral and neurophysiological methods to explore the neuroprotective function of hCG and hCG receptors in a mouse model of preterm and term brain injury. The central hypothesis of this project is that central hCG receptor activation by hCG in the injured term and preterm mouse brain reduces cerebral dysfunction and decreases neuronal degeneration via a PKA/ERK-mediated pathway. This research can serve as a translatable platform for the development of hCG and/or its mechanisms in the prevention and treatment of the devastating neurological effects brought on by neonatal cerebral injury.

摘要