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 four clinically relevant areas of CNS inflammation. 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. In a second model, we have begun to explore the inflammatory process in aged brain. Many diseases of the aging brain, such as Alzheimer's disease (AD),Parkinson's disease and amyotrophic lateral sclerosis, appear to have an inflammatory component. For example, the only drugs known to slow the progression of AD are anti-inflammatory in action. Specifically, we are examining the inflammatory process following traumatic brain injury. Such injuries are markedly worse in the aged. Our third area of research is in the area of gene therapy. The success of gene therapeutic methods, both in the brain and elsewhere, have been limited by the immune system's rejection of the newly transfected cells. We are currently examining the immune response to gene therapy protocols within the mouse brain. 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 late appearing cytokines with a wider therapeutic window. 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 TUNEL method for detection of apoptosis, we have begun to unravel the cell types, cytokines, chemokines, apoptotic genes, and adhesion molecules involved in CNS inflammation.

Kyrkanides, S.K., Miller, J.H., Brouxhon, S.M., Olschowka, J.A., and Federoff, H.J., ß-hexosaminidase lentiviral vectors: transfer into the CNS via systemic administration. Molecular Brain Res., 133(2)286-298, 2005.

Moore, A.H., Olschowka, J.A., Williams, J.P., Okunieff, P., and O’Banion, M.K., Regulation of prostaglandin E2 synthesis after brain irradiation.  Int. J. Radiation Oncology Biol. Phys., 62(1) 267-272, 2005.

Lioy, D.T., Sheridan, P.A., Hurley, S.D., Walton, J.R., Martin, A.M., Olschowka, J.A. and Moynihan, J.A. Acute morphine exposure potentiates the development of HSV-1-induced encephalitis. J. Neuroimmunology, 2005, Dec 1, ePub.

Lai, Y-C., Shaftel, S., Miller, J., Talents, R., Pinkert, C., Olschowka, J., Dickerson, I., Puzas, J., O’Banion, M.K., and Kyrkanides, S. Intra-articular induction of IL-1beta expression in the adult mouse results in joint pathology, dysfunction and pain. Arthritis and Rheumatism, 2005, in press.

Moore, A.H., Olschowka, J.A., Williams, J.P., Paige, S.L. and O’Banion, M.K., Radiation-induced edema is dependent on cyclooxygenase 2 activity in muse brain. Radiation Res. 161:153-160, 2004.

Moore, A.H., Olschowka, J.A.,and O’Banion, M.K.,   Intraparenchymal administration of interleukin-1beta induces cyclooxygenase-2-mediated expression of membrane- and cytosolic-associated prostaglandin E synthases in mouse brain.  J Neuroimmunol. 148(1-2):32-40, 2004.