Traumatic brain injury (TBI) increases the chances of one being affected by Alzheimer's disease (AD), what is not known is how TBI contributes to the onset and development of AD. In addressing the question, the author explores the neuropathological and behavioral consequences of single as well as repetitive mild traumatic brain injury (mTBI) in transgenic mice (Tg2576) which express mutant precursor protein of human beings, elevated levels of brain Ab and increased levels of Ab deposits is also demonstrated. This article uses the recently developed model of mild TBI mouse that craniotomy is not necessary, and the result produces very minimal damage to the brain structure. This model is used to determine whether single versus repetitive mTBI augments of AD is like amyloidosis. Accordingly, studies have also been conducted to examine the effects of single or repetitive mTBI on the motor and cognitive behaviors as well as the start and progression of amyloidosis in transgenic as well as the wild-type mice model at 2 d and 9 and 16 weeks subsequent to mTBI. Levels of isoprostanes and markers of lipid peroxidation (LPO) are also monitored by linking evidence of oxidative damage and Alzheimer's disease pathology (Kanamaru et al., 2015). Studies have provided experimental evidence implicating traumatic brain injury in Alzheimer's disease mechanisms through brain AB accumulation and LPO augmentation.
Link Between Traumatic Brain Injury and Alzheimer’s Disease
Presently, studies have shown that there is a clear positive link between traumatic brain injury episodes and the increased levels of amyloid deposition in the model of Tg mouse of Alzheimer's disease amyloidosis. Specifically, it is demonstrated that repetitive mTBI in Tg2576 mice resulted in considerable acceleration of deposition of amyloid by image analysis immunohistochemical stained brain sections and the increased production and accumulation of AB40 and AB42 in the soluble and insoluble homogenate of the brain by sensitive AB ELISA. Furthermore, it is also found that there is significantly greater cognitive function impairment in MWM tests and elevated urinary and brain levels of isoprostane isomer that is very well characterized and with a reliable index of oxidative stress. Also, traumatic brain injury is found to be one of the most robust environmental risk factors for Alzheimer's disease.
A mild mouse TBI model has been developed to elucidate the role that heads trauma in Tg mouse plays in developing age-dependent AD-like amyloidosis attributable to expression of a double APP mutation present in the Swedish FAD patients. This strategy has also facilitated the dissection of differences in the effect of single versus repetitive mTBI in the Tg2576 mouse model of AD amyloidosis.
Effects of Traumatic Brain Injury
Although there are no comparable data on isoprostanes beyond those provided for the effects of TBI in WT rodents, assessment of isoprostane isomers such as 8, 12-iso-iPF2a-VI can be utilized to analyze the scope of LPO and AD and the animal models of such disorders. Previous studies on Tg2576 showed that isoprostane levels started increasing after a few months before the appearance of plague in the brain parenchyma, that is at nine months of these mice, and here it is shown that isoprostane levels became significantly higher in the Tg2576 mice subjected to repetitive mTBI as compared to the sham-treated Tg2576 mice at week nine subsequent to surgery and well before there was a noticeable growth of amyloid deposition at 4 months after mTBI. Reasonable evidence on the difference between the levels of isoprostanes in single versus repetitive mTBI outcomes in Tg mice, in this case, is unclear. However, they reflect the greater extent of brain-barrier damage or cellular stress in experiments of repetitive mTBI.
Hypotheses stating that oxidative damage is mechanistically involved in the degeneration of Alzheimer's disease brain have been supported by various reports. Additionally, quite a number of studies on Tg mice as well as those of aging Downs syndrome patients suggest that amyloid deposition in the brain is preceded by oxidative stress increase. Consistently, mTBI produced a rapid increase in LPO in the Tg mice as presented by the brain and urinary 8, 12-iso-iPF2a-VI, and this is concurrent with the Ab production and accumulation in the brain.
Since then, a lot of studies have given a proposition that oxidative stress upholds amyloid aggregation and fibril creation. From this aspect of view, an increased amount of isoprostane could, therefore, show that the oxidative damage enhances or reflects fibrillization and on top of that the role in upholding APP processing to errand creation of amyloid genic Ab peptides. Thus, it is believable that increased amounts of oxidative stress brought in by mTBI in the Tg2576 mice probably could increase the processing to bring in more AB. This thereby augments AB fibrillization and aggregation into SPs.
Successively, as this formation continues, it probably might serve to more and more rise LPO and the general levels of oxidative stress in the brain. Nevertheless, other studies are more so recommended to clarify the specific flow of events that associate oxidative stress to ABamyloidosis and brain degeneration in Alzheimer's disease. Although this model amongst others of Alzheimer's disease amyloidosis does not fully summarize the full Alzheimer's disease phenotype, and there are plentiful other alterations in the motor and cognitive aptitudes in mice and humans, animal models of Alzheimer's disease brain pathology contribute significant tentative systems for explanation mechanisms of AB and TBI-induce neurodegeneration. In summary, a hypothesis tested that brain injuries are in relation to an environmental risk factor for Alzheimer's disease although some other multiple genetic and epigenetic factors play some role in affecting the individuals. Since the effects of traumatic brain injury go way beyond the impact site evolving over a number of months after an episode of traumatic brain injury, it is can be concluded that these diffuse and sustained traumatic brain injury effects may be mediated in part by current LPO induced by traumatic brain injury.
Kanamaru, T., Kamimura, N., Yokota, T., Iuchi, K., Nishimaki, K., & Takami, S. et al. (2015). Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease. Neuroscience Letters, 587, 126-131.
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