Early H-1 brain injury and behavioral outcome in rats

大鼠早期 H-1 脑损伤和行为结果

基本信息

批准号：
7257226
负责人：
ROSLYN HOLLY FITCH
金额：
$ 18.31万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-10 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7257226
关键词：
Address Adolescent Adult Affect Age Anatomy Animals Architecture Auditory Behavioral Benchmarking Birth Birth trauma Brain Brain Hypoxia-Ischemia Brain Injuries Child Clinical Clinical Data Clinical Treatment Cognitive Cognitive deficits Cortical Dysplasia Data Depressed mood Development Developmental Disabilities Disruption Dose Erythropoietin Event Exposure to Female Future Hand Hippocampus (Brain)Holly Homeostasis Human Hypoxia Impairment Incidence Individual Infant Injury Knowledge Language Language Development Language Disorders Lead Learning Learning Disabilities Literature Location Longevity Low Birth Weight Infant Lung Measures Memory Memory impairment Modeling Neonatal Neurologic Neuroprotective Agents Outcome Oxygen Pathology Pattern Performance Perinatal Brain Injury Perinatal Hypoxia Population Premature Infant Prematurity of fetus Process Radial Range Rattus Relative (related person)Reporting Research Research Personnel Risk Rodent ST5 Protein ST5 gene Secondary to Sensory Process Severities Sex Characteristics Sex Functioning Short-Term Memory Stroke Structure Testing Time Upper arm Very Low Birth Weight Infant Work base behavior measurement boys clinically relevant day deprivation design girls gray matter indexing injured insight male morris water maze neonatal hypoxic-ischemic brain injury neonate neurodevelopment neuropathology postnatal prenatal programs pup relating to nervous system research study response sex skills trend visual process visual processing white matter white matter damage white matter injury

项目摘要

DESCRIPTION (provided by applicant): Neurological impairment due to oxygen deprivation (hypoxia/ischemia or HI) is a common mechanism of damage to the premature and/or very low birth-weight (VLBW) infant brain. Such injuries contribute to a significant increase in the incidence of long-term behavioral and cognitive deficits (such as language and learning disabilities) among premature/VLBW populations. However, many factors impede a direct assessment of neurodevelopmental trends in this population. For example, precise details on timing, extent, and location of brain damage are often difficult to obtain in neonates, limiting the ability to statistically assess relationships between HI injury and long term outcome. Fortunately related research has shown that neonatal induction of HI injuries in rodents produces a neuropathology strikingly similar to that seen in human premature/VLBW neonates. Several reports show a decrement in learning and cognitive skill for rats with neonatal HI injuries, but no research of which we are aware has examined the impact of experimental manipulations of injury on long term outcome using a variety of functional assessments - the central aim of this proposal. Specifically, the studies proposed here will assess the consequences of timing and severity of an induced neonatal HI injury (measured by age at injury and duration of hypoxia) on cognitive/behavioral outcome in a rat model. We will also assess interactions between HI injury and sex, based on clinical evidence of gender differences in response to HI injury, as well as potential ameliorative effects of a neuroprotective agent on long-term behavioral outcome and neuropathology. Dependent variables will include behavioral measures (sensory processing indices, and spatial and non-spatial learning indices, from juveniles and adults), electrophysiological indices, and post mortem anatomical indices. Convergent data will allow for a comprehensive statistical assessment of the impact of experimental variables on functional and anatomical outcome, as well as correlations between function and anatomy. Our findings will contribute general information to the field of neurodevelopmental assessment, with specific implications for clinical treatment of premature/VLBW infants. Future applications may include improvements in cognitive outcome predictions following HI injury, as well as increased insight on amelioration treatment and therapy for infants suffering early HI injuries.

描述（由申请人提供）：由于缺氧而引起的神经损害（缺氧/缺血或HI）是对早产和/或非常低的出生体重（VLBW）婴儿大脑损害的常见机制。这种伤害导致长期行为和认知缺陷（例如语言和学习障碍）的发生率显着增加。但是，许多因素阻碍了对该人群中神经发育趋势的直接评估。例如，在新生儿中通常很难获得有关时间，程度和位置的精确细节，从而限制了统计评估HI损伤与长期结局之间关系的能力。幸运的是，相关的研究表明，啮齿动物中HI损伤的新生儿诱导产生的神经病理学与人类早产/VLBW新生儿中的神经病理非常相似。几份报告表明，新生儿HI伤害的大鼠学习和认知技能的下降，但我们知道，使用各种功能评估，我们知道的研究已经检查了损伤实验操作对长期结局的影响，这是该提案的主要目的。具体而言，此处提出的研究将评估诱发的新生儿HI损伤的时间和严重程度的后果（通过损伤和缺氧持续时间在大鼠模型中的认知/行为结果测量）。我们还将根据对HI损伤的性别差异的临床证据以及神经保护剂对长期行为结果和神经病理学的潜在改善作用来评估HI损伤与性别之间的相互作用。因变量将包括行为度量（感官处理指数，空间和非空间学习指数，来自少年和成人），电生理指数以及验尸后解剖学指数。收敛数据将允许对实验变量对功能和解剖结局的影响以及功能与解剖学之间的相关性进行全面的统计评估。我们的发现将为神经发育评估领域提供一般信息，对早产/VLBW婴儿的临床治疗具有具体影响。未来的应用可能包括改善HI受伤后认知结果预测，以及对早期HI损伤的婴儿的改善治疗和治疗的见解。