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Cholinergic Protection in Ischemic Brain Injury

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Neuroprotective Therapy for Stroke and Ischemic Disease

Part of the book series: Springer Series in Translational Stroke Research ((SSTSR))

Abstract

The cholinergic system is essential for maintenance of cognitive, autonomic, and immune homeostasis in mammals. Existing preclinical studies suggest that endogenous cholinergic tone elevated by ischemic or traumatic brain injury may serve as a combination autotherapy aiming at multiple distinct cellular and molecular pathways with converging neuroprotective and anti-inflammatory efficacies. These hardwired endogenous protective mechanisms can be augmented by cholinergic treatments including nicotinic receptor agonists, positive allosteric modulation, and vagus nerve stimulation. The α7 subtype of nicotinic acetylcholine receptors (nAChRs) is uniquely positioned as a promising therapeutic target in stroke and traumatic brain injury because of the neuroprotective anti-inflammatory efficacy of α7 nAChR activation and the ubiquitous expression of α7 nAChRs in mammalian neuronal, glial, and immune tissues. This article further explores the therapeutic promise of endogenous α7-dependent neuroprotective and anti-inflammatory injury-induced autotherapy which may act as an important physiological function of these ubiquitous receptors and may hold significant translational potential.

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Abbreviations

ATP:

Adenosine triphosphate

CaMKII:

Ca2+/calmodulin-dependent kinase-II

CDP-choline:

Cytidine diphosphate-choline

DMV:

The dorsal motor nucleus of the vagus

JAK:

Janus kinase

NAb:

The nucleus ambiguus

NfkB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PI3K/Akt:

Phosphatidylinositol-4,5-bisphosphate 3-kinase/serine/threonine-specific protein kinase

RK:

Extracellular signal-regulated kinase

STAT:

Signal transducer and activators of transcription

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Acknowledgments

I thank the William and Ella Owens Foundation for support and Dr. William Culp for insightful discussions.

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  1. Institute for Healthy Aging, Center for Neuroscience Discovery, University of North Texas Health Science Center, 3500 Camp Bowie Blvd., CBH 501, Fort Worth, TX, 76107, USA

    Victor V. Uteshev Ph.D.

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  1. Department of Neurology and Neurosurgery, Cedars-Sinai Medical Center, Los Angeles, California, USA

    Paul A. Lapchak

  2. Loma Linda University School of Medicine, Loma Linda, California, USA

    John H. Zhang

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Uteshev, V.V. (2017). Cholinergic Protection in Ischemic Brain Injury. In: Lapchak, P., Zhang, J. (eds) Neuroprotective Therapy for Stroke and Ischemic Disease. Springer Series in Translational Stroke Research. Springer, Cham. https://doi.org/10.1007/978-3-319-45345-3_17

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