NEURAL AND BEHAVIORAL PLASTICITY AFTER BRAIN DAMAGE

脑损伤后的神经和行为可塑性

• 批准号: 3408126
• 负责人: TIMOTHY SCHALLERT
• 金额: $ 14.02万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-08-01 至 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3408126
• 关键词: amphetamines; anticonvulsants; behavior test; brain injury; brain subcortex; cerebral cortex; diazepam; experimental brain lesion; immobilization of body part; inhibitor /antagonist; laboratory rat; limb movement; longitudinal animal study; nervous system regeneration; neural degeneration; neural plasticity; neuroanatomy; neuropharmacology; neurophysiology; neurotransmitters; nonhuman therapy evaluation; psychomotor function; sensorimotor system; stimulant /agonist

We will continue to investigate the disruptive effects of diazepam and related drugs on recovery of sensorimotor function after unilateral damage to anteromedial cortical regions. Moreover, experiments carried out during the current funding period have led to an additional focus on novel anatomical events that appear to have an important role in restoration of function. The general strategy outlined in this proposal is to manipulate the recovery process using disruptive or facilitating treatments, to define sensitive periods during which the treatments are effective, to analyze behavior in detail, and to describe relevant structural changes in subcortical and cortical regions of the ipsilateral and contralateral hemisphere. We very recently found that in response to injury of the sensorimotor cortex a large increase in thickness occurred exclusively in the homotopic area of the contralateral hemisphere, followed by a reduction in thickness but not a complete return to baseline. Maximum increases in thickness corresponded in time with excessive use of the unimpaired limb in home-cage postural-motor behavior, especially movements having weight-bearing/shifting consequences. This raises the possibility that the morphological changes may be related to behavioral strategies adopted by the animals to compensate for lesion-induced impairments in the contralateral forelimb. In a followup experiment, we found that in the region of increased thickness there was a time-dependent dramatic growth of layer V neuronal dendrites, followed by partial pruning. Pruning may represent an adjustment to the recovery of more symmetrical limb use or may correspond to improved cross-midline coordination of both forelimbs. We plan to characterize further the novel biphasic (growth-pruning) dendritic sequence and its potential behavioral significance, and to manipulate each phase independently by drug and behavioral interventions in an effort to establish how it might be involved in restoration of function after brain damage. For example, one sleeve casts or open-sleeve (control) casts will be used to permit use of the ipsilateral, contralateral, or both forelimbs during home-cage behaviors in rats with unilateral sensorimotor cortex lesions or sham operations. Preliminary results suggest that the dramatic arborization in the intact cortex occurs only after brain injury combined with limb use experience. The long-term goal is to better understand plasticity after brain damage while assessing time-dependent influences of pharmacological and behavioral interventions.

我们将继续研究地西泮和地西泮的破坏性影响 相关药物对单侧损伤后感觉运动功能恢复的影响 至前内侧皮质区域。 此外，期间进行的实验 当前的资助期导致了对新颖性的额外关注 似乎对恢复具有重要作用的解剖事件 功能。 该提案中概述的总体策略是操纵 使用破坏性或促进性治疗的恢复过程，以定义 治疗有效的敏感期，分析 详细的行为，并描述相关的结构变化 同侧和对侧的皮质下和皮质区域 半球。 我们最近发现，为了应对受伤 感觉运动皮层厚度的大幅增加仅发生在 对侧半球的同伦面积，然后减少 厚度但未完全恢复到基线。 最大增加量 厚度与过度使用未受损肢体的时间相对应 家笼姿势运动行为，尤其是具有以下特征的运动 负重/转移的后果。 这提出了一种可能性，即 形态变化可能与动物所采取的行为策略有关 动物来补偿损伤引起的损伤 对侧前肢。 在后续的实验中，我们发现 厚度增加的区域存在随时间变化的急剧增长 V层神经元树突，然后进行部分修剪。 修剪可以 代表对更对称肢体使用的恢复的调整，或者可能 对应于改善的两个前肢的跨中线协调。 我们 计划进一步表征新型双相（生长修剪）树突 序列及其潜在的行为意义，并操纵每个 通过药物和行为干预独立阶段，以努力 确定它如何参与大脑功能的恢复 损害。 例如，单袖石膏或开袖（对照）石膏将 用于允许使用同侧、对侧或双前肢 单侧感觉运动皮层大鼠的家笼行为 病变或假手术。 初步结果表明，戏剧性的 完整皮质中的树枝化仅在脑损伤合并后发生 有肢体使用经验。 长期目标是更好地理解 脑损伤后的可塑性，同时评估时间依赖性影响 药物和行为干预。