Deep brain stimulation of the Nucleus Basalis of Meynert: the role of stimulation parameters in neurogenesis and cognitive recovery.

梅纳特基底核的深部脑刺激：刺激参数在神经发生和认知恢复中的作用。

• 批准号: 10551858
• 负责人: Deepak Kumbhare
• 金额: $ 14.6万
• 依托单位: LOUISIANA STATE UNIV HSC SHREVEPORT
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10551858
• 关键词: Adverse effects; Alzheimer' s Disease; Amyloid; Animal Model; Animals; Anterior; Anxiety; Arousal; Attention; Auditory; Basal Nucleus of Meynert; Cathodes; Cell Nucleus; Cells; Clinical; Clinical Treatment; Clinical Trials; Cognition; Cognitive; Data; Deep Brain Stimulation; Dementia; Disease; Economics; Electric Stimulation; Evaluation; Future; Goals; Health; Histologic; Hour; Immunoglobulin G; Individual; Learning; Lesion; Lewy Body Dementia; Lobar; Maintenance; Measures; Medial; Memory; Modeling; Modification; Monitor; Neocortex; Nerve Regeneration; Neuronal Differentiation; Nucleus Accumbens; Outcome; Parkinson' s Dementia; Persons; Play; Population; Prefrontal Cortex; Proliferating; Proteins; REM Sleep; Rattus; Residual state; Rest; Role; Sleep; Sleep Wake Cycle; Sleep disturbances; Stress; Thalamic structure; Toxin; Wakefulness; Work; awake; behavioral outcome; biological adaptation to stress; cerebral atrophy; cholinergic; cognitive process; cognitive recovery; cognitive testing; deep brain stimulator; demented; design; early phase clinical trial; effective therapy; electric field; entorhinal cortex; field study; improved; innovation; migration; mild cognitive impairment; neocortical; nerve stem cell; neuroblast; neurogenesis; neurorestoration; novel; pilot trial; preservation; prevent; response; simulation; social; subventricular zone; treatment strategy; vigilance

PROJECT SUMMARY The number of people living with dementia doubles every five years, creating an ever-growing health, social, and economic catastrophe for the future. There are currently no effective treatments for dementia. Dementia due to Alzheimers disease, Lewy Body dementia, and Parkinsons Disease dementia is associated with degeneration of the nucleus basalis if Meynert (NBM). This results in the loss of the cholinergic supply to the cortex, cortical atrophy, and the loss of a variety of abilities associated with that cortex. The potential to provide symptomatic relief through the electrical stimulation of the NBM has been recognized, with early clinical trials underway. On the other hand, the potential for NBM deep brain stimulation (DBS) to modify the course of the disease through stimulation induced neurogenesis has not been evaluated, despite multiple lines of evidence demonstrating stimulation induced neurogenesis in other stuctures. We have demonstrated this potential in our preliminary data. The goal of this proposal is charcterize and optimize this potential. To this end we will evaluate the neuroregenerative effects and cognitive improvements associated with continuous NBM stimulation in demented and control rats and monitor for adverse effects on sleep-wake cycles and stress. Because of the role that the NBM plays in sleep and the potential stress of always being alert and vigilant, we will evaluate ‘activity-dependent stimulation’ as an alternative strategy to optimize the positive effects of NBM stimulation on neurogenesis, learning, and health of the animal. The optimal parameters for disease modification will be important for the design of future clinical trials of NBM stimulation.

项目概要 患有痴呆症的人数每五年就会翻一番，造成健康、社会、 以及未来的经济灾难 目前尚无有效的痴呆症治疗方法。 由于阿尔茨海默病、路易体痴呆和帕金森病痴呆与 基底核变性（NBM），这会导致胆碱能供应的丧失。 皮质、皮质萎缩以及与该皮质相关的各种能力的丧失。 通过早期临床试验，人们已经认识到通过 NBM 电刺激可以缓解症状 另一方面，NBM 深部脑刺激（DBS）有可能改变该过程。 尽管有多种证据，但尚未对刺激诱导神经发生引起的疾病进行评估 在其他结构中证明刺激诱导神经发生我们已经在我们的研究中证明了这种潜力。 该提案的目标是描述和优化这一潜力。 评估与持续 NBM 相关的神经再生效应和认知改善 对痴呆大鼠和对照大鼠进行刺激，并监测对睡眠-觉醒周期和压力的不利影响。 由于 NBM 在睡眠中发挥的作用以及始终保持警觉和警惕的潜在压力，我们 将评估“活动依赖性刺激”作为优化 NBM 积极效果的替代策略 对动物神经发生、学习和健康的刺激 疾病的最佳参数。 修改对于 NBM 刺激的未来临床试验的设计非常重要。