The immunology of traumatic brain injury: a prime target for Alzheimer’s disease prevention
Open Access
- 1 August 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Neuroinflammation
- Vol. 9 (1), 185
- https://doi.org/10.1186/1742-2094-9-185
Abstract
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.Keywords
This publication has 101 references indexed in Scilit:
- Can consuming flavonoids restore old microglia to their youthful state?Nutrition Reviews, 2010
- EGCG functions through estrogen receptor‐mediated activation of ADAM10 in the promotion of non‐amyloidogenic processing of APPFEBS Letters, 2010
- Microglial Phenotype Is Regulated by Activity of the Transcription Factor, NFAT (Nuclear Factor of Activated T Cells)Journal of Neuroscience, 2010
- Luteolin triggers global changes in the microglial transcriptome leading to a unique anti-inflammatory and neuroprotective phenotypeJournal of Neuroinflammation, 2010
- A Lack of Amyloid β Plaques Despite Persistent Accumulation of Amyloid β in Axons of Long‐Term Survivors of Traumatic Brain InjuryBrain Pathology, 2009
- Post‐injury baicalein improves histological and functional outcomes and reduces inflammatory cytokines after experimental traumatic brain injuryBritish Journal of Pharmacology, 2008
- Apigenin and luteolin modulate microglial activation via inhibition of STAT1-induced CD40 expressionJournal of Neuroinflammation, 2008
- HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in ratsBrain Research, 2008
- Blocking TGF-β–Smad2/3 innate immune signaling mitigates Alzheimer-like pathologyNature Medicine, 2008
- Inflammaging as a prodrome to Alzheimer's diseaseJournal of Neuroinflammation, 2008