Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke.
Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke.
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DOI：
10.1007/s12975-015-0409-7
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发表时间：
2015-08
影响因子：
6.9
通讯作者：
Novak V
中科院分区：
文献类型：
--
作者：
Lioutas VA;Alfaro-Martinez F;Bedoya F;Chung CC;Pimentel DA;Novak V
中风的治疗选择仍然有限。特别是，神经保护疗法总是无法在中风患者中产生预期的好处，尽管有坚实的理论和机制背景以及有希望的动物数据。胰岛素和胰岛素样生长因子-1(IGF-1)在能量平衡、神经元生长和分化等关键脑功能中起着关键作用。它们在急性缺血性卒中中可能表现出神经保护作用，其基础是血管扩张、抗炎和抗血栓作用，以及改善功能连接、神经元代谢、神经递质调节和重新髓鞘形成。鼻腔注射胰岛素对老年人的认知功能衰退有预防作用，而胰岛素样生长因子-1在改善急性缺血性中风动物模型的功能结果方面显示出潜在的益处。鼻腔给药途径提供了一种可行、耐受、安全、特别有效的给药途径，绕过血脑屏障，最大限度地分配到中枢神经系统(CNS)，没有全身副作用和首过代谢的缺点。本文综述了鼻腔注射胰岛素和胰岛素样生长因子-1对中风患者的神经保护作用。我们介绍了胰岛素和胰岛素样生长因子-1鼻腔给药的理论背景和病理生理机制，动物和人体研究，以及经鼻腔给药给药的安全性和可行性。
Treatment options for stroke remain limited. Neuroprotective therapies, in particular, have invariably failed to yield the expected benefit in stroke patients, despite robust theoretical and mechanistic background and promising animal data. Insulin and insulin-like growth factor 1 (IGF-1) play a pivotal role in critical brain functions, such as energy homeostasis, neuronal growth, and differentiation. They may exhibit neuroprotective properties in acute ischemic stroke based upon their vasodilatory, anti-inflammatory and antithrombotic effects, as well as improvements of functional connectivity, neuronal metabolism, neurotransmitter regulation, and remyelination. Intranasally administered insulin has demonstrated a benefit for prevention of cognitive decline in older people, and IGF-1 has shown potential benefit to improve functional outcomes in animal models of acute ischemic stroke. The intranasal route presents a feasible, tolerable, safe, and particularly effective administration route, bypassing the blood–brain barrier and maximizing distribution to the central nervous system (CNS), without the disadvantages of systemic side effects and first-pass metabolism. This review summarizes the neuroprotective potential of intranasally administered insulin and IGF-1 in stroke patients. We present the theoretical background and pathophysiologic mechanisms, animal and human studies of intranasal insulin and IGF-1, and the safety and feasibility of intranasal route for medication administration to the CNS.