Effect of Insulin on Neuroplasticity and Cognitive Rehabilitation

胰岛素对神经可塑性和认知康复的影响

基本信息

批准号：
9904720
负责人：
Catrina Sims Robinson
金额：
$ 20.18万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-02 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9904720
关键词：
Address Affect Animal Model Animals Anti-Inflammatory Agents Apoptotic Basic Science Brain Brain Injuries Brain region Centers of Research Excellence Cerebrospinal Fluid Clinic Clinical Investigator Cognition Cognitive Cognitive aging Data Dendritic Spines Diabetes Mellitus Diagnosis Diet Effectiveness Goals High Fat Diet Hippocampus (Brain)Hour Human Hyperinsulinism Insulin Insulin Resistance Insulin deficiency Ischemic Stroke Laboratories Lead Lesion Magnetic Resonance Imaging Memory Middle Cerebral Artery Occlusion Modeling Motor Mus Nervous System Physiology Neurologic Neuronal Plasticity Outcome Pathway interactions Peripheral Phenotype Play Property Proteins Recovery Recovery of Function Rehabilitation therapy Reporting Research Research Personnel Role Severities Stroke Structure Synapses Testing Therapeutic Time Tissues Translating Traumatic Brain Injury Work base behavior test brain health cognitive function cognitive rehabilitation comorbidity disability environmental enrichment for laboratory animals impaired glucose tolerance improved innovation motor recovery mouse model novel therapeutic intervention novel therapeutics post stroke programs stroke patient stroke recovery stroke rehabilitation stroke survivor synaptogenesis

项目摘要

There is a fundamental gap in understanding the importance of brain insulin levels in stroke recovery. This gap is important because of the significance of brain insulin with regard to neuroplasticity and the anti-inflammatory, anti-thrombotic, vasodilatory and anti-apoptotic properties of insulin, which play a vital role in recovery from brain injury. The long-term goal is to understand the role of comorbidities on brain health, specifically cognitive aging. The objective of this application is to investigate the role of reduced brain insulin and the therapeutic potential of intranasal insulin on long-term stroke recovery (4 months post-stroke). Insulin resistance, which is a common comorbidity among stroke survivors, leads to a deficiency of insulin in the brain. The central hypothesis is that increasing brain insulin levels will improve stroke recovery. This hypothesis is based on preliminary data produced in the applicant’s laboratory. The rationale for the proposed research is that brain insulin levels affect neuroplasticity, and intranasal insulin may offer a new therapeutic approach to improve recovery from stroke. This hypothesis will be tested by pursuing two specific aims: 1) Determine the impact of insulin deficiency in the brain on stroke recovery, and 2) Ascertain the therapeutic potential of intranasal insulin therapy on stroke recovery. Under Aim 1, stroke recovery (cognitive, sensorimotor and motor function) is assessed in a comorbid mouse model (high-fat diet) with brain insulin deficiency, and in a non-comorbid mouse model (standard diet) treated with intranasal insulin affibody molecules, which reduce brain insulin levels, following an ischemic stroke. Under the second aim, intranasal insulin therapy is implemented post-stroke to enhance rehabilitation-induced neuroplasticity and improve stroke recovery. The approach is innovative, because it utilizes a comorbid animal model of ischemic stroke, assesses long-term stroke recovery up to 4 months post-stroke, and uses intranasal insulin as a therapy to enhance neuroplasticity and improve stroke recovery. The proposed research is significant because it is expected to lead to the establishment of intranasal insulin as a potential therapy to enhance stroke recovery. Ultimately, the COBRE also will provide the unique opportunity to work with clinical investigators to translate this basic science research into the clinic.

理解脑胰岛素水平在中风恢复中的重要性存在根本的差距。这个差距很重要，因为脑胰岛素在神经塑性和抗炎药方面的重要性，胰岛素的抗栓性，血管舒张和抗凋亡特性，在从大脑中恢复中起着至关重要的作用受伤。长期目标是了解合并症在大脑健康方面的作用，特别是认知衰老。该应用的目的是调查脑胰岛素减少的作用和治疗潜力的作用长期中风恢复的鼻内胰岛素（冲程后4个月）。胰岛素抵抗，这是一种常见中风存活之间的合并症导致大脑中胰岛素的缺乏。中心假设是大脑胰岛素水平的提高将改善中风的恢复。该假设基于初步数据在申请人的实验室中生产。拟议研究的理由是大脑胰岛素水平会影响神经可塑性和鼻内胰岛素可能会提供一种新的治疗方法，以改善中风的恢复。该假设将通过追求两个具体目的来检验：1）确定胰岛素缺乏症对中风恢复的大脑，2）确定鼻内胰岛素治疗对中风的治疗潜力恢复。在AIM 1下，在合并症中评估了中风恢复（认知，感觉运动和运动功能）小鼠模型（高脂饮食）伴有脑胰岛素缺乏症和非瘤小鼠模型（标准饮食）在缺血性中风后，用鼻内胰岛素催化剂分子治疗，降低脑胰岛素水平。在第二个目的下，鼻内胰岛素治疗将在中风后实施，以增强康复引起的神经可塑性并改善中风恢复。这种方法是创新的，因为它利用了合并症缺血性中风的模型，评估势后4个月的长期中风恢复，并使用鼻内胰岛素作为一种疗法，可增强神经可塑性并改善中风恢复。拟议的研究很重要因为预计将导致建立鼻内胰岛素作为增强中风的潜在疗法恢复。最终，毛绒还将提供与临床研究人员合作的独特机会将这项基础科学研究转化为诊所。