RNS60, a physically-modified saline, inhibits glial activation, suppresses neuronal apoptosis and protects memory in a mouse model of traumatic brain injury

Traumatic brain injury (TBI) is a serious health issue that causes long-term neurological disability, particularly in young adults, athletes and war veterans. Despite the use of different medications or surgical procedures, no effective therapy is currently available to halt its pathogenesis. Here, we have undertaken a novel approach to reduce neuroinflammation and improve cognitive, social and locomotor behaviors in a mouse model of TBI. RNS60 is a physiologic saline solution containing oxygen nanobubbles that is generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. Recently we have delineated that RNS60 inhibits the expression of proinflammatory molecules in glial cells via type 1A phosphatidylinositol-3 kinase (PI3K)-mediated upregulation of IκBα. In this study, we found that TBI decreased the level of IκBα and increased the activation of NF-κB in hippocampus and cortex as monitored by the upregulation of p-p65. However, intraperitoneal administration of RNS60 increased and/or restored the level of IκBα and inhibited the activation of NF-κB in hippocampus and cortex of TBI mice. Accordingly, RNS60 treatment decreased the activation of astrocytes and microglia and reduced neuronal apoptosis in the brain of TBI mice. RNS60 treatment also reduced vascular damage, attenuated blood-brain barrier leakage and decreased the size of lesion in the brain of TBI mice. Importantly, RNS60 treated mice showed significant improvements in memory, social behavior and locomotor activities while displaying reduction in depression-like behaviors. These results delineate a novel neuroprotective property of RNS60 and suggest its possible therapeutic use in TBI.