Abstract
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1–40 or 1–42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.
Highlights
Traumatic brain injury (TBI) has emerged as a signature injury of the early 21st century
We investigated the effects of molecular hydrogen given in drinking water, a method of delivery that should be readily translatable to clinical situations, on the brain edema, tau pathology, neuroinflammation, and gene expression induced by controlled cortical impact (CCI), an animal model of TBI
CCI did not produce a remarkable increase in GFAP staining, but CCI mice treated with molecular hydrogen given in drinking water (mHW) had less GFAP staining that either sham or CCI mice (Figure 4)
Summary
Traumatic brain injury (TBI) has emerged as a signature injury of the early 21st century. Injuries that penetrate the skull are more rare but a very serious form of TBI [3]. TBI arises from a variety of injuries, the clincial endpoints that result and the mechanisms that drive the CNS towards those endpoints are thought to be shared among TBI’s, and by a host of neurodegenerative diseases [4,5]. These endpoints and mechanisms include brain edema, tauopathy, blood-brain barrier (BBB) disruption and dysfunction, and neuroinflammation [6,7,8]. Preventative and interventive therapeutics are needed to treat TBI as early as possible
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