The inflammatory processes that follow injury (trauma, stroke, seizure, infection, radiation, etc.) to the central nervous system (CNS) dramatically amplify the damage. For example, reduction of the inflammatory process following stroke has...
RECENT RESEARCH:
Models of CNS inflammation.
The inflammatory processes that follow injury (trauma, stroke, seizure, infection, radiation, etc.) to the central nervous system (CNS) dramatically amplify the damage. For example, reduction of the inflammatory process following stroke has been shown to limit the volume of damaged tissue by 2/3's. Our laboratory is currently working to better understand the mechanisms of inflammation within the CNS. Currently we are examining several clinically relevant areas of CNS inflammation, most in collaboration with Dr. Kerry O'Banion. First, we are using a model of damage to the CNS caused by gamma-irradiation. Treatment of brain tumors with radiation leads to long-term damage of the normal brain tissue, damage caused by a massive inflammatory response. This model will be expanded beginning in the fall of 2008 by a NIAID funded pilot project as we examine the effects of combined injuries, radiation and a peripheral injury, on the functioning of both brain and lung. In a related model, we are examining the effect of cosmic radiation (similar to the exposure received in space) on the CNS. Third, using several transgenic mouse models of Alzheimer's disease coupled with a model of chronic inflammation, we are exploring the possible beneficial effects of inflammation in the clearing of Aß plaque pathology. Fourth, in a project begun this year, we are examining the potential brain injuring effects of underwater sound exposure. This project funded by the Office of Naval Research is interested in the use of sound exposure as a non-lethal weapon. Our final and newest area of research examines late appearing cytokines following brain injury. While suppression of acute pro-inflammatory cytokines has worked well in animal models, they have not proven useful clinically. We are now examining the late appearing cytokine HMGB-1 and its receptors (RAGE, TLR4 and TLR2) in a model of traumatic brain injury. With a better understanding, we hope to limit the inflammatory response and thus improve the effectiveness of therapy. Using techniques such as light microscopic immunocytochemistry, in situ hybridization, computerized image analysis, quantitative real time RT-PCR, and the immunohistochemical methods for detection of apoptosis, we have begun to unravel the cell types, cytokines, chemokines, apoptotic genes, and adhesion molecules involved in CNS inflammation. With the aid of a pilot grant from the Schmitt Foundation, we are now beginning to examine to role of CNS inflammation in the development of seizure activity. Following a variety of inflammation models (radiation-induced, Alzheimer's transgenic mice, peripheral inflammation, etc), we have begun to record EEG's from mice to determine alterations in susceptibility to seizure activity.
PUBLICATIONS: Cherry JD; Williams JP; O'Banion MK; Olschowka JA "Thermal injury lowers the threshold for radiation-induced neuroinflammation and cognitive dysfunction." Radiation research. 2013; 180(4):398-406. Ghosh S; Wu MD; Shaftel SS; Kyrkanides S; Laferla FM; Olschowka JA; O'Banion MK "Sustained interleukin-1ß overexpression exacerbates tau pathology despite reduced amyloid burden in an Alzheimer's mouse model." The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013; 33(11):5053-64. Cherry JD; Liu B; Frost JL; Lemere CA; Williams JP; Olschowka JA; O'Banion MK "Galactic cosmic radiation leads to cognitive impairment and increased aß plaque accumulation in a mouse model of Alzheimer's disease." PloS one. 2012; 7(12):e53275. . Hein AM, Stasko, MR, Matousek SB, Scott-McKean JJ, Maier SF, Olschowka JA, Costa AC, O'Banion MK. Sustained hippocampal IL-1ß overexpression impairs contextual and spatial memory in transgenic mice. Brain Behav. Immun. 2009, PMCID: PMC2818290
Dilmanian FA, Rusek A, Fois GR, Olschowka J, Desnoyers NR, Park JY, Dioszegi I, Dane B, Wang R, Tomasi D, Lee H, Hurley SD, Coyle PK, Meek AG, O'Banion MK
International journal of radiation oncology, biology, physics.. 2012 October 184 (2):514-9. Epub 02/17/2012.