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Free Radic Biol Med. 2018 Aug 20;124:328-341. doi: 10.1016/j.freeradbiomed.2018.06.026. Epub 2018 Jun 27.

The cysteine-rich whey protein supplement, Immunocal®, preserves brain glutathione and improves cognitive, motor, and histopathological indices of traumatic brain injury in a mouse model of controlled cortical impact.

Author information

1
University of Denver, Department of Biological Sciences, Denver, CO 80208, United States. Electronic address: lizignowski@gmail.com.
2
University of Denver, Department of Biological Sciences, Denver, CO 80208, United States. Electronic address: aimee.n.winter@gmail.com.
3
University of Denver, Knoebel Institute for Healthy Aging, Denver, CO 80208, United States. Electronic address: ng.duval@gmail.com.
4
University of Denver, Knoebel Institute for Healthy Aging, Denver, CO 80208, United States. Electronic address: holly.fleming@du.edu.
5
University of Denver, Department of Biological Sciences, Denver, CO 80208, United States. Electronic address: tywall28@gmail.com.
6
University of Denver, Department of Biological Sciences, Denver, CO 80208, United States. Electronic address: evan.manning@ucdenver.edu.
7
University of Denver, Department of Biological Sciences, Denver, CO 80208, United States. Electronic address: koza.lilia@gmail.com.
8
University of Colorado Cancer Center, Aurora, CO 80045, United States. Electronic address: kendra.huber@ucdenver.edu.
9
University of Colorado Cancer Center, Aurora, CO 80045, United States. Electronic address: natalie.serkova@ucdenver.edu.
10
University of Denver, Department of Biological Sciences and Knoebel Institute for Healthy Aging, 2155 E. Wesley Ave., Denver, CO 80208, United States. Electronic address: daniel.linseman@du.edu.

Abstract

Traumatic brain injury (TBI) is a major public health problem estimated to affect nearly 1.7 million people in the United States annually. Due to the often debilitating effects of TBI, novel preventative agents are highly desirable for at risk populations. Here, we tested a whey protein supplement, Immunocal®, for its potential to enhance resilience to TBI. Immunocal® is a non-denatured whey protein preparation which has been shown to act as a cysteine delivery system to increase levels of the essential antioxidant glutathione (GSH). Twice daily oral supplementation of CD1 mice with Immunocal® for 28 days prior to receiving a moderate TBI prevented an ~ 25% reduction in brain GSH/GSSG observed in untreated TBI mice. Immunocal® had no significant effect on the primary mechanical injury induced by TBI, as assessed by MRI, changes in Tau phosphorylation, and righting reflex time or apnea. However, pre-injury supplementation with Immunocal® resulted in statistically significant improvements in motor function (beam walk and rotarod) and cognitive function (Barnes maze). We also observed a significant preservation of corpus callosum width (axonal myelination), a significant decrease in degenerating neurons, a reduction in Iba1 (microglial marker), decreased lipid peroxidation, and preservation of brain-derived neurotrophic factor (BDNF) in the brains of Immunocal®-pretreated mice compared to untreated TBI mice. Taken together, these data indicate that pre-injury supplementation with Immunocal® significantly enhances the resilience to TBI induced by a moderate closed head injury in mice. We conclude that Immunocal® may hold significant promise as a preventative agent for TBI, particularly in certain high risk populations such as athletes and military personnel.

KEYWORDS:

Cognitive function; Glutathione; Motor function; Neuroprotection; Traumatic brain injury

PMID:
29940352
PMCID:
PMC6211803
[Available on 2019-08-20]
DOI:
10.1016/j.freeradbiomed.2018.06.026

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