John A. Olschowka, Ph.D.

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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.

PUBLICATIONS:

Kyrakanides S, Miller AW, Miller JN, Tallents RH, Brouxhon SM, Olschowka ME, O'Banion MK, Olschowka JA. Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration. J Neuroimmunol. 203 (2008):50-57,.

Shaftel, S. S.; Carlson, T. J.; Olschowka, J. A.; Kyrkanides, S.; Matousek, S. B.; O'Banion, M. K.;. "Chronic interleukin-1beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood brain barrier permeability without overt neurodegeneration". J Neurosci 27 (2007): 9301-9.

Kyrkanides, S.; Miller, J. N.; Tallents, R. H.; Brouxhon, S. M.; Centola, G. M.; Olschowka, J. A.;. "Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype". J Neuroimmunol 188 (2007): 39-47.

Shaftel, S. S.; Kyrkanides, S.; Olschowka, J. A.; Miller, J. N.; Johnson, R. E.; O'Banion, M. K.;. "Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology". J Clin Invest 117 (2007): 1595-604.

Lioy, D.T.; Sheridan, P.A.; Hurley, S.D.; Walton, J.R.; Martin, A.M.; Olschowka, J.A.; Moynihan, J.A. "Acute morphine exposure potentiates the development of HSV-1-induced encephalitis." J. Neuroimmunology 172 (2006): 9-17.

Current Appointments

• Associate Professor - Department of Neurobiology and Anatomy (SMD)

Education
PhD Anatomy	Univ of Cal Davis	1978
MS Anatomy	Univ of Cal Davis	1974
BS Zoology	Univ of Cal Davis	1973

Post-Doctoral Training & Residency
John Hopkins University School of Medicine: Research Associate, Department of Neurology.	1979
Johns Hopkins University School of Medicine: Postdoctoral Fellow, Department of Cell Biology and Anatomy.	1978 - 1980

Fellowship Awards
NIH Postdoctoral Fellowship; Johns Hopkins University School of Medicine, Department of Anatomy; Study of catecholamine fibers within the developing cerebellum;	1978 - 1980

Lab Website

http://www.urmc.rochester.edu/labs/O-Labs/

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Recent Journal Articles
Showing the 5 most recent journal articles. (63 available)
Kyrakanides S, Miller AW, Miller JN, Tallents RH, Brouxhon SM, Olschowka ME, O'Banion MK, Olschowka JA. "Peripheral blood mononuclear cell infiltration and neuroinflammation in the HexB-/- mouse model of neurodegeneration." J Neuroimmunol. 203 (2008): 50-57.
Shaftel SS; Kyrkanides S; Olschowka JA; Miller JN; Johnson RE; O'Banion MK. "Sustained hippocampal IL-1 beta overexpression mediates chronic neuroinflammation and ameliorates Alzheimer plaque pathology." The Journal of clinical investigation. 2007; 117(6):1595-604.
Kyrkanides S; Miller JN; Tallents RH; Brouxhon SM; Centola GM; Olschowka JA. "Intraperitoneal inoculation of Sandhoff mouse neonates with an HIV-1 based lentiviral vector exacerbates the attendant neuroinflammation and disease phenotype." Journal of neuroimmunology. 2007; 188(1-2):39-47. Epub 2007 Jun 18.
Shaftel SS; Carlson TJ; Olschowka JA; Kyrkanides S; Matousek SB; O'Banion MK. "Chronic interleukin-1beta expression in mouse brain leads to leukocyte infiltration and neutrophil-independent blood brain barrier permeability without overt neurodegeneration." The Journal of neuroscience : the official journal of the Society for Neuroscience. 2007; 27(35):9301-9.
Lioy, D.T.; Sheridan, P.A.; Hurley, S.D.; Walton, J.R.; Martin, A.M.; Olschowka, J.A.; Moynihan, J.A. "Acute morphine exposure potentiates the development of HSV-1-induced encephalitis." J. Neuroimmunology 172 (2006): 9-17.