INDUCED NEOCORTICAL MALFORMATIONS

诱发新皮质畸形

• 批准号: 6301906
• 负责人: GLENN D ROSEN
• 金额: $ 13.96万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2001-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6301906
• 关键词: age difference; brain injury; developmental neurobiology; disease /disorder model; dyslexia; experimental brain lesion; immunocytochemistry; intercellular connection; laboratory rat; neocortex; neural information processing; neuroanatomy; neuropathology; neuropsychological tests; newborn animals; stimulus /response

Accumulated evidence suggests that multiple neurologic systems are aberrantly organized in individuals with developmental dyslexia, ranging from developmental anomalies of the neocortex to defects in lower level sensory systems. It is hypothesized that these anomalies are correlated, and further that they influence each other in a top-down manner. Specifically, we hypothesize that early focal neocortical injury sets into motion a cascade of events that results in the disruption of connectionally-related anatomic structures - a disruption that may in turn lead to defects in the function of fast components of primary sensory systems. The proposed set of experiments will explore the anatomic substrates of developmental dyslexia - a uniquely human disorder - with an animal model of neonatal focal neocortical damage. This animal model involves the induction of focal neuronal migration disorders by small freezing lesions to the developing cortical plate of the rat. These lesions result in the formation of an area of dysgenetic cortex resembling 4-layered microgyria, and are associated with fast component temporal processing deficits in this animal. It is the goal of this proposal to investigate how early neocortical damage might affect the organization of the developing brain connectionally and cytoarchitectonically, and how to ameliorate the anatomic effects of early brain injury. Specifically, we will attempt to determine (1) the effects of neonatal neocortical injury in different locations on neuronal connectivity of the rat, first by examining connections in adulthood and then by determining their formation developmentally; (2) the effects of neonatal neocortical injury on the volumetric and cellular morphometry of connectionally-related and - unrelated cortical and subcortical regions by measuring architectonic volume, neuronal size and density, and neuronal activation; (3) whether the reported amelioration of behavior by enrichment is associated with changes in the volumetric, connectional, and morphometric characteristics of the brain, and (4) the effects of age of lesion on the formation developmental cortical anomalies.

积累的证据表明多个神经系统是 在发育阅读障碍的人群中异常组织 从新皮层的发育异常到较低级别的缺陷 感觉系统。假设这些异常是相关的， 此外，他们以自上而下的方式相互影响。 具体而言，我们假设早期的局灶性新皮质损伤将 运动一系列事件导致破坏 与连接相关的解剖结构 - 依次可能 导致主要感觉的快速组成部分的功能缺陷 系统。拟议的一组实验将探索解剖学 发育阅读障碍的底物 - 一种独特的人类疾病 - 新生儿局灶性新皮质损伤的动物模型。这个动物模型 涉及小型诱导局灶性神经元迁移障碍 将大鼠发育中的皮质板的冰冻病变。这些 病变导致形成类似的失去障碍皮质区域 4层微毛，与快速分量时间有关 该动物的处理缺陷。这是该提议的目标 调查新皮层损害可能如何影响组织 发展的大脑在连接和细胞结构上，以及如何 改善早期脑损伤的解剖作用。具体来说，我们 将尝试确定（1）新生儿新皮质损伤的影响 在大鼠神经元连通性的不同位置，首先 在成年后检查连接，然后确定其形成 发展（2）新生儿新皮质损伤对 与连接相关的体积和细胞形态计量法和 - 通过测量建筑型，无关的皮质和皮质下区域 体积，神经元的大小和密度以及神经元激活； （3）是否 据报道，通过富集改善行为的改善与 体积，连接和形态计量特征的变化 大脑和（4）病变年龄对形成的影响 发育性皮质异常。