We are currently investigating the use of engineered cerium oxide nanoparticles (CeONP) for the treatment of TBI. CeONP have been used for years in materials science as a coating to reduce oxidation, but its potential use in biology and medicine is only beginning to be investigated. The physicochemical properties of CeONP suggest a strong ability to scavenge free radicals, and it thus has potential applications in disease states involving the production of free radicals. TBI induces the production of damaging free radicals which have the ability to cause extensive damage to intracellular constituents and cell membranes. This project aims to determine the potential of implementing CeONP as a potential treatment for reducing oxidative stress and free radical damage induced by TBI. This work is being conducted in collaboration with Dr. Beverly Rzigalinski from the nearby Virginia College of Osteopathic Medicine in Blacksburg and is funded by the National Institute of Neurological Disorders and Stroke (NINDS). To date, findings from this project include:

· Preliminary experiments suggest that CeONP are neuroprotective following experimental TBI

· CeONP improve functional outcome following experimental TBI 

Cerium Oxide Nanoparticles in TBI

Research

TBI induces persistent memory impairments that often interfere with a patients ability to lead a normal life.  Using a variety of methodologies, our lab is interested in understanding the mechanisms underlying both anterograde and retrograde memory dysfunction in the injured brain.  Recent findings in this line of research include:

· Working memory processes are particularly vulnerable to TBI.  In high-demand tasks that require interactions between frontal and hippocampal structures, brain-injured animals display rapid forgetting.

· Brain-injury may selectively impair the initial stages (e.g., encoding) or memory formation. Brain-injured animals who are given an extra opportunity to acquire a task display rates of forgetting similar to control animals. This suggests that rehabilitative treatments that target the early stages of the learning and memory process may be especially helpful.

· Retrograde memory impairment following TBI may be due to retrieval failure. By providing a specific reminder cue, some memories that were previously inaccessible can be recalled.

Mechanisms of Chronic Memory Dysfunction in TBI

Traumatic brain injury (TBI) is a leading cause of death and disability throughout the world. The focus of our lab is understanding and treating the pathophysiology of secondary brain injury, with a special emphasis on mechanisms contributing to poor functional outcome. Secondary brain injury is the catch-all term used to refer to the complex cascade of neurodegenerative events continuing for weeks or even months after the moment of injury. The ultimate goal of our research is to develop therapeutic treatments or interventions that will counteract these secondary events and improve the lives of those living with TBI. We are particularly interested in understanding cognitive impairment following TBI and developing treatments that will enhance memory and other behavioral functions in the chronically injured brain.

Overview

The fluorite lattice structure of cerium oxide

Recent work in our lab suggests that certain plant compounds may be useful for the treatment of neurodegenerative conditions such as TBI.  We are currently investigating the use of select flavonoids for treating TBI-induced behavioral impairment.

 

Phytochemicals for the Treatment of TBI