Spinal serotonin in cerebral palsy

脑瘫中的脊髓血清素

基本信息

批准号：
9511923
负责人：
Alexander Drobyshevsky
金额：
$ 34.04万
依托单位：
NORTHSHORE UNIVERSITY HEALTHSYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-30 至 2020-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9511923
关键词：
2 year old Anatomy Animal Model Animals Biomechanics Brain Brain Hypoxia-Ischemia Brain Injuries Cerebral Palsy Child Clinical Research Conceptions Corticospinal Tracts Development Diagnosis Diffusion Disease Electrophysiology (science)Etiology FDA approved Family Felidae Fiber Functional disorder Gene Expression Profiling High Pressure Liquid Chromatography Human Hyporeflexia Image In Vitro Incidence Injury Interneurons Interruption Light Live Birth Maintenance Measures Modeling Motor Motor Neurons Muscle Hypertonia Muscle Spasticity Muscle Tonus Neuromodulator Neurons Neurotransmitters Newborn Infant Norepinephrine Oryctolagus cuniculus Palliative Care Pathway interactions Patients Perinatal Pharmaceutical Preparations Property Receptor Gene Reflex action Regulation Rehabilitation therapy Research Risk Rodent Role Selective Serotonin Reuptake Inhibitor Serotonergic System Serotonin Serotonin Agents Serotonin Agonists Serotonin Antagonists Spinal Spinal Cord Synapses Testing Therapeutic Intervention Time antenatal base clinically relevant data modeling experimental study falls fetus hypoxia innovation motor deficit motor disorder neonatal care neurotransmission non-invasive imaging novel postnatal postsynaptic prevent public health relevance receptor serotonin receptor serotonin transporter stretch reflex white matter injury

项目摘要

DESCRIPTION (provided by applicant): The incidence of cerebral palsy is 1-2 per 1000 live births and has not declined in recent decades despite the improvement of neonatal care. Currently there is no cure for cerebral palsy and pathophysiology of motor deficits in this disorder is poorly understood. The proposal explores previously not described mechanism of muscle hypertonia in cerebral palsy after fetal hypoxia-ischemia brain injury acting via abnormally increased input of brain serotonin to spinal cord. We hypothesize that the elevated spinal serotonin increases spinal cord excitability and acts in development of motor deficits in cerebral palsy. A novel clinically relevant rabbit model of fetal hypoxia-ischemia, resulted in pronounced motor deficits in newborns, including muscle hypertonia, will be used to elucidate the proposed pathophysiological mechanism and therapeutic interventions. The proposed hypothesis will be tested using a combination of non-invasive imaging, electrophysiological recordings, biomechanical analysis of motor deficits and gene expression analysis. First, we will test whether white matter injury to the descending supraspinal projections and increased spinal serotonin explain postnatal muscle hypertonia after antenatal H-I independently or act synergistically. Second, we will test whether hypertonia could be directly caused by 5HT increasing intrinsic excitability of spinal motoneurons or due to altered synaptic excitation, including both pre- and postsynaptic modulation of synaptic inputs to motoneurons by 5HT, and decreased supraspinal inhibition due to white matter injury.

描述（由适用提供）：脑瘫的事件是每1000例活产1-2，尽管有新生儿护理的改善，但近几十年来却没有下降。目前，尚无法治愈这种疾病中运动缺陷的脑瘫和病理生理学的治疗方法。该提案探讨了先前未描述胎儿缺氧 - 缺血性脑损伤的肌肉高渗的机制，该脑损伤是通过新型的胎儿低氧缺血性临床相关的兔子兔模型作用的，导致新生儿的明显运动缺乏症，包括肌肉高血压，包括肌肉hypertonia，将用于肌肉高血压，以促进肌肉的机制。提出的假设首先，我们将测试白质造成脊柱上跨性别预测的损伤，并增加了静脉肌肉肌肉在H-I后产后肌肉高血压的解释，或者是独立行动的。其次，我们将测试是否可以直接由5HT引起脊柱运动神经元的固有兴奋性或由于突触兴奋的改变，包括在5HT上对运动神经元的突触输入前和突触后调节，以及由于白物质损伤而降低了肩部抑制。