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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.

在理解脑胰岛素水平在中风恢复中的重要性方面存在根本性的差距。这一差距是重要的，因为脑胰岛素在神经可塑性和抗炎方面的重要性，胰岛素的抗血栓形成、血管扩张和抗凋亡特性，在脑损伤的恢复中发挥重要作用，损伤长期目标是了解合并症对大脑健康的作用，特别是认知老化。本申请的目的是研究脑胰岛素减少的作用和鼻内胰岛素对长期卒中恢复（卒中后4个月）的影响。胰岛素抵抗是一种常见的中风幸存者的合并症会导致大脑中胰岛素缺乏。核心假设是，增加脑胰岛素水平将改善中风恢复。这一假设是基于初步数据在申请人的实验室生产。这项研究的基本原理是，大脑胰岛素水平会影响神经可塑性和鼻内胰岛素可能提供一种新的治疗方法，以改善中风的恢复。这一假设将通过追求两个具体目标来检验：1）确定胰岛素缺乏对糖尿病患者的影响。脑卒中恢复，2）确定鼻内胰岛素治疗卒中的治疗潜力复苏根据目标1，在共病患者中评估卒中恢复（认知、感觉运动和运动功能），脑胰岛素缺乏的小鼠模型（高脂肪饮食）和非共病小鼠模型（标准饮食）在缺血性中风后，用鼻内胰岛素受体分子治疗，该分子降低脑胰岛素水平。在第二个目标下，在中风后实施鼻内胰岛素治疗以增强康复诱导的神经可塑性和改善中风恢复。这种方法是创新的，因为它利用了一种共病动物缺血性卒中模型，评估卒中后长达4个月的长期卒中恢复，并使用鼻内胰岛素作为增强神经可塑性和改善中风恢复的疗法。所提出的研究是有意义的因为它有望导致鼻内胰岛素作为一种潜在的治疗方法的建立，复苏最终，COBRE还将提供与临床研究人员合作的独特机会，将这些基础科学研究转化为临床。