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Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke

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Abstract

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.

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Abbreviations

IN:

Intranasal

AIS:

Acute ischemic stroke

ICH:

Intracerebral hemorrhage

BBB:

Blood–brain barrier

CNS:

Central nervous system

IGF-1:

Insulin-like growth factor 1

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Acknowledgments

The authors wish to thank Katharina Dormanns, PhD candidate Brains Trust Research Group, BlueFern Supercomputing Unit (University of Canterbury), for her contribution in the design of the figures presented in the paper.

Dr V.N. has received grants from the NIH–National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (5R21-DK-084463-02 and 1R01 DK103902-01A1) and National Institute on Aging (NIA) (1R01-AG-0287601-A2) and National Instittute of Diabetes and Digestive and Kidney Diseases  (1R01DK103902-01A1) related to this study, and V.N. received salaries from these grants.

Conflict of Interest

Drs Lioutas, Alfaro-Martinez, Bedoya, Chung, Pimentel, and Novak declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Neurology, Division of Cerebrovascular Diseases, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Palmer 127, Boston, MA, 02215, USA

    Vasileios-Arsenios Lioutas, Freddy Alfaro-Martinez, Francisco Bedoya, Chen-Chih Chung, Daniela A. Pimentel & Vera Novak

  2. Department of Neurology, Shuang Ho Hospital, Taipei, Taiwan

    Chen-Chih Chung

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  1. Vasileios-Arsenios Lioutas
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  2. Freddy Alfaro-Martinez
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  3. Francisco Bedoya
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  5. Daniela A. Pimentel
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  6. Vera Novak
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Correspondence to Vasileios-Arsenios Lioutas.

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Lioutas, VA., Alfaro-Martinez, F., Bedoya, F. et al. Intranasal Insulin and Insulin-Like Growth Factor 1 as Neuroprotectants in Acute Ischemic Stroke. Transl. Stroke Res. 6, 264–275 (2015). https://doi.org/10.1007/s12975-015-0409-7

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  • DOI: https://doi.org/10.1007/s12975-015-0409-7

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