A significant cause of brain injury is the disruption to the nitric oxide (NO) signaling pathway. Following a physiological stress, such as after a traumatic brain injury (TBI), NO functions as both an important regulator of the cerebral blood flow and a potential neurotoxin. In the U.S., approximately 2.2 million individuals suffer a TBI annually; and, the annual cost of treatment is $76 billion. The role of NO in the pathogenesis of brain injuries remains poorly understood because of the complex biological characteristics of NO and the fact that most investigations NO provide discrete endpoint data rather than detailing the temporal evolution of neuronal degeneration post insult. The ability to monitor these quantities with higher temporal resolution may lead to better understanding of the relationship between NO and TBI, potentially leading to treatments that enable partial restoration of physiological blood flow and prevention of secondary injuries. An in situ sensor that continuously measures the behavior of NO and its byproducts in real-time with high temporal resolution would allow for close monitoring of the evolution of a TBI and its likelihood to cause irreparable harm. The proposed research aims to develop a sensing platform that can continuously monitor NO in real time without compromising the accuracy of the measurement, the superb temporal resolution, and the flexibility across various media. Magnetic complex colloids will be use to translate chemical signals in cell cultures to observable morphological responses, namely changes in magnetoresistance and optical transparency. This objective will be accomplished in two aims.
In Aim 1, the goal is to develop a system of magnetic complex colloids whose responses to NO or its byproducts will lead to the change in the magnetoresistance that is then measured in real time. Specifically, NO-responsive surfactants will mediate the reaction and alter the interfacial tensions, causing the magnetic complex colloids to change their morphologies and magnetoresistance. The sensor developed in Aim 1 will be used to measure the bioactivity of NO generated from cell cultures in Aim 2. Namely, mouse macrophages will be activated by bacterial lipopolysaccharide (LPS) and interferon-? (IFN-?) to produce NO, while mouse fibroblasts will serve as the negative control. Bio-inert responsive surfactants will be used to ensure the lack of cytotoxicity. Cell vitality and NO production will be evaluated continuously as a function of time. The proposed studies will provide a unique handle of continuous measurement of the behavior of NO, which may lead to new strategies for treatment and prevention of secondary brain injury. Furthermore, the proposed sensors that can non-invasively translate chemical signals to magnetic readings have the potential to be broadly useful for a number of other sensing applications.
Understanding the key signaling pathway of nitric oxide after a traumatic brain injury could potentially lead to new strategies for the treatment and prevention of secondary brain injuries. Despite the tremendous progress of in vitro models, most investigations of the effects of TBI have provided discrete endpoint data, rather than detailing the temporal evolution of neuronal degeneration immediately post insult, leading to an incomplete characterization and contradicting correlations. Here I propose the development of a novel sensor that can continuously measure nitric oxide in real time without compromising the accuracy of the measurement, the superb temporal resolution, and the flexibility across various media.
| Truong, Tran N B; Savagatrup, Suchol; Jeon, Intak et al. (2018) Modular Synthesis of Polymers Containing 2,5-di(thiophenyl)-N-arylpyrrole. J Polym Sci A Polym Chem 56:1133-1139 |
| Wang, Pan; Jeon, Intak; Lin, Zhou et al. (2018) Insights into Magneto-Optics of Helical Conjugated Polymers. J Am Chem Soc 140:6501-6508 |
| Schroeder, Vera; Savagatrup, Suchol; He, Maggie et al. (2018) Carbon Nanotube Chemical Sensors. Chem Rev : |
