The immunology of traumatic brain injury: a prime target for Alzheimer’s disease prevention
1 James A. Haley Veterans’ Administration Hospital, 13000 Bruce B. Downs Blvd., Tampa, FL, 33612, USA
2 Department of Psychiatry and Behavioral Neurosciences, Neuroimmunology Laboratory, Morsani College of Medicine, University of South Florida, 3515 E. Fletcher Ave., Tampa, FL, 33613, USA
3 Department of Neurosurgery and Brain Repair, Center of Excellence for Aging and Brain Repair, Morsani College of Medicine, University of South Florida, 12901 Bruce. B. Downs. Blvd., Tampa, FL, 33612, USA
4 Department of Psychiatry and Behavioral Neurosciences, Silver Child Development Center, Rashid Laboratory for Developmental Neurobiology, Morsani College of Medicine, University of South Florida, 3515 E. Fletcher, Tampa, FL, 33613, USA
5 Department of Psychiatry and Behavioral Neurosciences, University of South Florida, Morsani College of Medicine, 3515 E. Fletcher Avenue, Tampa, FL, 33613, USA
Journal of Neuroinflammation 2012, 9:185 doi:10.1186/1742-2094-9-185Published: 1 August 2012
A global health problem, traumatic brain injury (TBI) is especially prevalent in the current era of ongoing world military conflicts. Its pathological hallmark is one or more primary injury foci, followed by a spread to initially normal brain areas via cascades of inflammatory cytokines and chemokines resulting in an amplification of the original tissue injury by microglia and other central nervous system immune cells. In some cases this may predispose individuals to later development of Alzheimer’s disease (AD). The inflammatory-based progression of TBI has been shown to be active in humans for up to 17 years post TBI. Unfortunately, all neuroprotective drug trials have failed, and specific treatments remain less than efficacious. These poor results might be explained by too much of a scientific focus on neurons without addressing the functions of microglia in the brain, which are at the center of proinflammatory cytokine generation. To address this issue, we provide a survey of the TBI-related brain immunological mechanisms that may promote progression to AD. We discuss these immune and microglia-based inflammatory mechanisms involved in the progression of post-trauma brain damage to AD. Flavonoid-based strategies to oppose the antigen-presenting cell-like inflammatory phenotype of microglia will also be reviewed. The goal is to provide a rationale for investigations of inflammatory response following TBI which may represent a pathological link to AD. In the end, a better understanding of neuroinflammation could open therapeutic avenues for abrogation of secondary cell death and behavioral symptoms that may mediate the progression of TBI to later AD.