Effect of Insulin on Neuroplasticity and Cognitive Rehabilitation

在对大脑胰岛素水平在中风康复中的重要性的理解上存在着根本性的差距。这一差距 之所以重要，是因为脑胰岛素在神经可塑性和抗炎方面具有重要意义， 胰岛素的抗血栓、血管扩张和抗凋亡特性在脑复苏中起着至关重要的作用 受伤。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。 这项应用的目的是研究减量脑胰岛素的作用和治疗潜力 鼻腔胰岛素对卒中远期康复(卒中后4个月)的影响。胰岛素抵抗是一种常见的 中风幸存者的共病会导致大脑中胰岛素的缺乏。中心假设是 提高大脑胰岛素水平将促进中风的康复。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中的胰岛素水平会影响 神经可塑性和鼻内胰岛素可能为促进中风的康复提供一种新的治疗方法。 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 2)确定鼻腔内胰岛素治疗对中风的治疗潜力 恢复。在目标1中，中风的恢复(认知、感觉运动和运动功能)是在共病中评估的。 脑胰岛素缺乏的小鼠模型(高脂饮食)和非共病小鼠模型(标准饮食) 在缺血性中风后，鼻腔注射胰岛素粘附体分子，可降低脑内胰岛素水平。 在第二个目标下，卒中后实施鼻腔胰岛素治疗，以加强康复诱导 神经可塑性和改善中风的康复。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4个月的长期卒中恢复，并使用鼻腔 胰岛素作为增强神经可塑性和改善中风康复的治疗方法。这项拟议的研究具有重要意义 因为它有望导致鼻内胰岛素作为一种潜在的治疗中风的方法的建立 恢复。最终，Cobre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临床。

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.