AXONAL GROWTH IN THE CHRONICALLY INJURED SPINAL CORD

慢性损伤脊髓的轴突生长

• 批准号: 6639407
• 负责人: John D. Houle
• 金额: $ 28.19万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-08-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6639407
• 关键词: axon; brain stem; chronic disease /disorder; dorsal horn; embryo /fetus cell /tissue; fluorescent dye /probe; gene induction /repression; immunocytochemistry; laboratory rat; nervous system regeneration; nervous system transplantation; neurogenetics; neuronal guidance; neuronal transport; neurotrophic factors; peripheral nervous system; spinal cord; spinal cord injury

DESCRIPTION: (Verbatim from the Applicant's Abstract) The long term goals of the proposal are to determine the extent to which modulation of the local injury site, combined with trophic factor support and neural tissue transplantation can lead to structural repair of the chronically injured spinal cord. The specific aims address the hypothesis that combinations of experimental interventions in the chronic state after injury can promote axonal regeneration and integration across an injury site. It will also be determined whether progressive changes in chronically injured neurons influence their ability to respond to these interventive approaches and whether non-neuronal cells associated with the injury site modulate the neuronal response to injury and to trophic factor treatment. Aim I will utilize an established SCI-peripheral nerve graft model to determine how treatments of the graft spinal cord interface with compounds that modulate the non-neuronal cell response to injury can effectively promote axonal growth beyond the PN graft, into the dorsal horn of the spinal cord. The second aim will determine if a combination of neurotrophic factors and fetal tissue transplantation can increase axonal growth from a PN graft, into the spinal cord. Experiments for Aim III will determine why the regenerative effort of some neurons at different post injury intervals appears to be greater than that exhibited by other neurons. Neuronal survival, axonal retraction and changes in the expression of regeneration associated genes at various stages after spinal cord injury and in response to trophic factor treatment will be measured in relation to the regenerative response of specific brainstem neuron populations. In aim IV, changes in the cellular and biochemical composition of nonneuronal cells at a chronic lesion site and after trophic factor treatment will be examined by immunocytochemical labeling and multiprobe ribonuclease protection assays. We will compare these changes with the regenerative effort of factor-treated neurons observed in the previous Aims to reach and understanding of the impact of non-neuronal cell responses on the ability to promote regeneration. Overall, these experiments will provide valuable information about cellular and molecular aspects of the neuronal and non-neuronal response to long term injury and will assist in the design of interventive therapies to repair the chronically injured spinal cord.

描述：（逐字从申请人的摘要中）长期 该提案的目标是确定 调节当地伤害部位，结合营养因子 支撑和神经组织移植会导致结构 修复长期受伤的脊髓。具体目标 解决实验组合的假设 受伤后慢性状态的干预措施可以促进轴突 伤害部位的再生和整合。也将是 确定长期受伤的渐进变化是否 神经元影响他们应对这些干预措施的能力 方法以及非神经元细胞是否与 损伤部位调节对损伤和营养的神经元反应 因子处理。目的，我将利用已建立的Sci-Fipheral 神经移植模型，以确定移植脊柱的治疗方法 带有调节非神经元细胞的化合物的脐带界面 对伤害的反应可以有效地促进轴突生长 PN移植物进入脊髓的背喇叭。第二个目标 将确定神经营养因子和胎儿的结合 组织移植可以增加PN移植物的轴突生长， 进入脊髓。 AIM III的实验将确定为什么 某些神经元在不同后受伤后的再生努力 间隔似乎大于其他展览 神经元。神经元存活，轴突缩回和变化 再生在各个阶段的再生相关基因的表达 脊髓损伤和对营养因子治疗的反应 根据特定的再生反应进行测量 脑干神经元种群。在AIM IV中，细胞的变化 非神经元细胞的生化组成在慢性 病变部位和营养因素治疗将通过 免疫细胞化学标记和多核核酸酶保护 测定。我们将将这些变化与再生努力进行比较 在先前的目标中观察到的因子处理的神经元 并理解非神经元细胞反应对 促进再生的能力。总体而言，这些实验 将提供有关细胞和分子的宝贵信息 长期神经元和非神经元反应的方面 受伤，将有助于设计干预疗法 修复长期受伤的脊髓。

项目成果

Nerve growth factor (NGF)-treated nitrocellulose enhances and directs the regeneration of adult rat dorsal root axons through intraspinal neural tissue transplants.

神经生长因子 (NGF) 处理的硝化纤维通过椎管内神经组织移植增强并指导成年大鼠背根轴突的再生。

• DOI: 10.1016/0304-3940(89)90478-3
• 发表时间: 1989
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Houle,JD;Johnson,JE
• 通讯作者: Johnson,JE

PEGylated interferon-beta modulates the acute inflammatory response and recovery when combined with forced exercise following cervical spinal contusion injury.

• DOI: 10.1016/j.expneurol.2010.01.009
• 发表时间: 2010-06
• 期刊: EXPERIMENTAL NEUROLOGY
• 影响因子: 5.3
• 作者: Sandrow-Feinberg, Harra R.;Zhukareya, Victoria;Santi, Lauren;Miller, Kassi;Shumsky, Jed S.;Baker, Darren P.;Houle, John D.
• 通讯作者: Houle, John D.

Exercise after spinal cord injury as an agent for neuroprotection, regeneration and rehabilitation.

• DOI: 10.1016/j.brainres.2015.03.052
• 发表时间: 2015-09-04
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Sandrow-Feinberg HR;Houlé JD
• 通讯作者: Houlé JD

Peripheral nerve grafts after cervical spinal cord injury in adult cats.

• DOI: 10.1016/j.expneurol.2010.06.011
• 发表时间: 2010-09
• 期刊: EXPERIMENTAL NEUROLOGY
• 影响因子: 5.3
• 作者: Cote, Marie-Pascale;Hanna, Amgad;Lemay, Michel A.;Ollivier-Lanvin, Karen;Santi, Lauren;Miller, Kassi;Monaghan, Rebecca;Houle, John D.
• 通讯作者: Houle, John D.

Trophic factor modulation of c-Jun expression in supraspinal neurons after chronic spinal cord injury.

慢性脊髓损伤后脊髓上神经元 c-Jun 表达的营养因子调节。

• DOI: 10.1006/exnr.1998.6954
• 发表时间: 1998
• 期刊: Experimental neurology.
• 作者: Houle,JD;Schramm,P;Herdegen,T
• 通讯作者: Herdegen,T