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

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.

Assessment of Long-Term Effects of Sports-Related Concussions: Biological Mechanisms and Exosomal Biomarkers

“…In some cases, astrogliosis persisted for up to 28 days post-TBI, which was the longest time point analyzed post-injury in these studies (Susarla et al, 2014). Our group has similarly observed astrogliosis in mice exposed to mTBI induced by controlled cortical impact (see Figure 1; Ignowski et al, 2018). In mice subjected to repeated mTBIs, long-term cognitive deficits were associated with persistent astrogliosis up to one-year post-injury (Mannix et al, 2013).…”

“…For instance, a single unilateral impact in un-anesthetized mice induced rapid tauopathy within 24 h of injury, which persisted and progressed to the contralateral uninjured cortex by 5.5 months post-injury (Tagge et al, 2018). Several other models of single or repetitive mTBIs also produce aberrant Tau pathology (Kane et al, 2012;Luo et al, 2014;Petraglia et al, 2014;Yang et al, 2015;Ignowski et al, 2018). Of note, un-anesthetized mice administered 6 concussive impacts daily for 7 days, displayed elevated cortical p-Tau immunoreactivity up to 6 months post-mTBI (Petraglia et al, 2014).…”

Early‐life N‐arachidonoyl‐dopamine exposure increases antioxidant capacity of the brain tissues and reduces functional deficits after neonatal hypoxia in rats

“…We may propose that NADAs' ability to reduce oxidative stress in cells (Bobrov et al, 2008; Grabiec and Dehghani, 2017) resulted in decrease of basal ROS production and increased glutathione antioxidant buffer capacity. Previous findings on traumatic brain injury suggest that a strategy aimed at sustaining or enhancing brain GSH levels may be a viable approach to mitigate secondary injury and the subsequent long term cognitive, physical, and emotional deficiencies (Ignowski et al, 2018).…”

Whey Protein Concentrate WPC-80 Intensifies Glycoconjugate Catabolism and Induces Oxidative Stress in the Liver of Rats

“…Due to its varied composition, whey is commonly supplemented to emaciated patients (e.g., during convalescence or cancer cachexia), children with cow’s milk protein allergy and sportsmen to increase their muscle mass [ 1 , 4 ]. Whey proteins are also a valuable source of sulphuric amino acids: cysteine and methionine, crucial for the synthesis of reduced glutathione (GSH) [ 5 ]. GSH reveals strong antioxidant properties, which affects the proper functioning of the body, both healthy and ill [ 5 ].…”

“…Whey proteins are also a valuable source of sulphuric amino acids: cysteine and methionine, crucial for the synthesis of reduced glutathione (GSH) [ 5 ]. GSH reveals strong antioxidant properties, which affects the proper functioning of the body, both healthy and ill [ 5 ].…”