RESEARCH: Neuroinflammation in CNS Injury and Alzheimer's Disease.
Twenty years ago evidence from epidemiological studies and investigations of human brain pathology suggested the hypothesis that innate immune activation of the brain, a term now referred to as neuroinflammation, might contribute to the pathogenesis of Alzheimer's and other brain diseases. Based on our pioneering work in the area of cyclooxygenase-2 and inflammation, we initiated a research program that focuses on understanding the role of neuroinflammation in Alzheimer's and other neurodegenerative diseases. Studies conducted in the laboratory with human brain tissue, neuronal cell culture models and mouse models of acute injury and neurodegeneration have pointed to a prominent role for specific proinflammatory cytokines and bioactive prostaglandins in promoting neuroinflammation. Interestingly, our current work in Alzheimer's disease has revealed a potential protective role for neuroinflammation and has led to a focus on the influence of glial expressed cytokines and infiltrating peripheral cells on brain pathology, utilizing genetic and pharmacological approaches in a variety of mouse models. In complementary work, we also have active preclinical projects in the area of brain radiation injury, a critical problem for individuals receiving radiotherapy for brain tumors or bone marrow transplantation. The main goal is to understand the role of neuroinflammation and oxidative stress in promoting injury and to determine whether therapeutic interventions targeting these processes can alleviate late radiation effects, including cognitive changes
Cherry, J.D., B. Liu, J.L. Frost, C.A. Lemere, J.P. Williams, J.A. Olschowka and M.K. O'Banion. 2012. Galactic cosmic radiation leads to cognitive impairment and increased Ab plaque accumulation in a mouse model of Alzheimer's disease. PLOS ONE 7:e53275. PMCID in process.
Dilmanian, F.A., A.L. Jenkins, J. Olschowka, Z. Zhong, J.Y. Park, N.R. Desnoyers, S. Sobotka, G.R. Fois, C.R. Messina, M. Morales, S.D. Hurley, L.A. Trojanczyk, S. Ahmad, N. Shahrabi, P.K. Coyle, A.G. Meek and M.K. O'Banion. 2012. X-ray microbeam irradiation of the contusion-injured rat spinal cord temporarily improves hind-limb function. Rad. Res. Dec 5 [Epub ahead of print]. PMCID in process.
Wu, M.D., A.M. Hein, M.J. Moravan, S.S. Shaftel, J.A. Olschowka and M.K. O'Banion. 2012. Adult murine hippocampal neurogenesis is inhibited by sustained IL-1? and not rescued by voluntary running. Brain Behav. Immun. 26:292-300. PMCID: PMC3258353
Matousek, S.B., S. Ghosh, S.S. Shaftel, S. Kyrkanides, J.A. Olschowka and M.K. O'Banion. 2012. Chronic IL-1?-mediated neuroinflammation mitigates amyloid pathology in a mouse model of Alzheimer's disease without inducing overt neurodegeneration. J. Neuroimmune Pharmacol. 7:156-164. PMCID: PMC3302720
Hein, A. M., T. J. Zarcone, D. B. Parfitt, S. B. Matousek, D. M. Carbonari, J. A. Olschowka and M. K. O'Banion. 2012. Behavioral, structural and molecular changes following long-term hippocampal IL-1? overexpression in transgenic mice. J. Neuroimmune Pharmacol. 7:145-155. PMCID: PMC3214690
Kyrkanides S., R.H. Tallents, J.N. Miller, M.E. Olschowka, R. Johnson, M. Yang, J.A. Olschowka, S.M. Brouxhon and M.K. O'Banion. 2011. Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice. J. Neuroinflammation 8:112. PMCID: PMC3179730
Moravan, M.J., D.A. Olschowka, J.P. Williams and M.K. O'Banion. 2011. Cranial irradiation leads to acute and persistent neuroinflammation with delayed increases in T-cell infiltration and CD11c expression in C57BL/6 mouse brain. Radiat. Res. 176:459-473. PMCID: PMC3191189.