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Neural transplants to promote respiratory plasticity after spinal cord injury

神经移植促进脊髓损伤后呼吸可塑性

基本信息

批准号：
10238115
负责人：
Michael Aron Lane
金额：
$ 33.61万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-15 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10238115
关键词：
Address Adult Anatomy Animals Astrocytes Behavior Brain-Derived Neurotrophic Factor Breathing Cell Survival Cell Therapy Cell Transplantation Cells Cervical Cervical spinal cord injury Chronic Clinical Contusions Cues Data Electrodes Electrophysiology (science)Genes Glutamates Goals Growth Heterogeneity Hypoxia Impairment Implant Injury Interneurons Ipsilateral Maps Modeling Morbidity - disease rate Motor Motor Neurons Motor Pathways Muscle Neuroglia Neuronal Plasticity Neurons Oligodendroglia Paralysed Pathway interactions Pattern Phenotype Phrenic Motor System Plethysmography Population Population Heterogeneity Proliferating Rattus Recovery Regenerative capacity Reporting Research Respiration Respiration Disorders Respiratory Diaphragm Respiratory Muscles Respiratory physiology Site Source Spinal Spinal Cord Spinal cord injury Stem cell transplant Supporting Cell Synapses System Testing Therapeutic Therapeutic Intervention Tissues Training Transplantation Treatment Efficacy Work anatomical tracing awake axon growth axon guidance base clinically relevant designer receptors exclusively activated by designer drugs experience experimental study functional plasticity gene therapy improved improved functioning improved outcome injured innovation mortality mortality risk motor recovery nerve stem cell novel novel strategies post-transplant progenitor programs receptor relating to nervous system repaired respiratory stem cell therapy synaptic pruning therapeutic target therapy outcome ventilation

项目摘要

Impaired breathing is a devastating consequence of cervical spinal cord injury (SCI), representing a significant burden to injured people and increasing the risk of mortality. Respiratory dysfunction and associated secondary complications remain the leading cause of morbidity and mortality in people with cervical SCI. Particularly concerning are reports indicating that the number of cervical SCIs has increased in recent years. While there is mounting clinical and experimental evidence for spontaneous improvements in respiration, the extent of recovery – or functional plasticity – remains incomplete. However, plasticity is reliant on spared neural substrates after incomplete spinal cord injury (SCI). Thus, the extent of recovery without therapeutic intervention and anatomical repair is limited. To address this limitation, and amplify plasticity and recovery of breathing following cervical SCI, the proposed work aims to use a novel cell therapy to promote repair of phrenic motor pathways that control function of the diaphragm – a respiratory muscle essential to breathing. Results from our recent experimental studies have demonstrated that transplantation of interneuron-rich neural progenitor cells at the site of injury can promote anatomical repair and improve respiratory function following SCI. Transplanted neural precursor cells survive, proliferate and become integrated with injured host spinal cord, contributing to repair of respiratory pathways. The experiments proposed here build upon our extensive experience with the phrenic motor system, to test a novel strategy for transplanting refined interneuronal precursors that are associated with phrenic function. Using a clinically relevant contusion model of cervical SCI, we will test whether transplanted neural progenitors can anatomically and functionally integrate with this phrenic system, and promote consistent, lasting recovery of diaphragm. Not only will these experiments test an innovative and promising treatment approach, but they will significantly improve our understanding of the therapeutic potential of a wide range of neuronal transplantation approaches, including many of the stem cell therapies currently being tested experimentally and clinically.

呼吸障碍是颈脊髓损伤（SCI）的一种严重后果