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

迈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: 10354896
• 负责人: Deepak Kumbhare
• 金额: --
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 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 2022-05-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10354896
• 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; Diffuse; 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; Proteins; REM Sleep; Rattus; Residual state; Rest; Role; Sleep; Sleep Wake Cycle; Sleep disturbances; Stress; Toxin; Wakefulness; Work; awake; base; 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; 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.

项目摘要 患有痴呆症的人数每五年翻倍，创造不断发展的健康，社交， 和未来的经济灾难。目前没有有效的痴呆疗法。失智 由于阿尔茨海默氏病，刘易体内痴呆和帕金森病痴呆症与 如果Meynert（NBM），则巴萨利核的变性。这导致胆碱能供应损失 皮质，皮质萎缩以及与该皮质相关的多种能力的丧失。提供的潜力 通过早期临床试验，已经确认了通过对NBM的电刺激的症状缓解 进行。另一方面，NBM深脑刺激（DB）的潜力改变了 通过刺激诱导的神经发生尚未评估疾病，目的地多行证据 证明模拟在其他统治中诱导的神经发生。我们已经在我们的 初步数据。该提案的目的是充电并优化这种潜力。为此，我们将 评估与连续NBM相关的神经创收效应和认知改善 刺激和控制大鼠的刺激，并监测对睡眠效果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“依赖于活动的模拟”作为优化NBM积极影响的替代策略 对动物的神经发生，学习和健康的刺激。疾病的最佳参数 修改对于设计NBM刺激的未来临床试验至关重要。