Chronic effects of blast injury on the microvasculature in a transgenic mouse model of Alzheimer's disease related Aβ amyloidosis

Background: Altered cerebrovascular function and accumulation of amyloid-beta (A beta) after traumatic brain injury (TBI) can contribute to chronic neuropathology and increase the risk for Alzheimer's disease (AD). TBI due to a blast-induced shock wave (bTBI) adversely affects the neurovascular unit (NVU) during the acute period after injury. However, the chronic effects of bTBI and A beta on cellular components of the NVU and capillary network are not well understood. Methods: We exposed young adult (age range: 76-106 days) female transgenic (Tg) APP/PS1 mice, a model of AD-like A beta amyloidosis, and wild type (Wt) mice to a single bTBI (similar to 138 kPa or similar to 20 psi) or to a Sham procedure. At 3-months or 12-months survival after exposure, we quantified neocortical A beta load in Tg mice, and percent contact area between aquaporin-4 (AQP4)-immunoreactive astrocytic end-feet and brain capillaries, numbers of PDGFR beta-immunoreactive pericytes, and capillary densities in both genotypes. Results: The astroglia AQP4-capillary contact area in the Tg-bTBI group was significantly lower than in the Tg-Sham group at 3-months survival. No significant changes in the AQP4-capillary contact area were observed in the Tg-bTBI group at 12-months survival or in the Wt groups. Capillary density in the Tg-bTBI group at 12-months survival was significantly higher compared to the Tg-Sham control and to the Tg-bTBI 3-months survival group. The Wt-bTBI group had significantly lower capillary density and pericyte numbers at 12-months survival compared to 3-months survival. When pericytes were quantified relative to capillary density, no significant differences were detected among the experimental groups, for both genotypes. Conclusion: In conditions of high brain concentrations of human A beta, bTBI exposure results in reduced AQP4 expression at the astroglia-microvascular interface, and in chronic capillary proliferation like what has been reported in AD. Long term microvascular changes after bTBI may contribute to the risk for developing chronic neurodegenerative disease later in life.

Automated summary

In this study, the chronic effects of blast-induced traumatic brain injury (bTBI) and amyloid-beta (Aβ) on cellular components of the neurovascular unit (NVU) and capillary network were investigated using transgenic mice. The results showed that bTBI exposure led to reduced AQP4 expression and chronic capillary proliferation in the presence of high brain concentrations of human Aβ. These long-term microvascular changes may increase the risk for developing chronic neurodegenerative disease later in life.