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: 10673535
• 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 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10673535
• 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.

项目总结