Impact of age on acute post-TBI neuropathology in mice expressing humanized tau: a Chronic Effects of Neurotrauma Consortium Study

• Published in: Brain injury 2018-08, Vol.32 (10), p.1285-1294
• Main Authors: Mouzon, Benoit, Saltiel, Nicole, Ferguson, Scott, Ojo, Joseph, Lungmus, Carlyn, Lynch, Cillian, Algamal, Moustafa, Morin, Alexander, Carper, Benjamin, Bieler, Gayle, Mufson, Elliott J., Stewart, William, Mullan, Michael, Crawford, Fiona
• Format: Article
• Language: English
• Subjects: age; animal models; axonal injury; inflammation; neurodegeneration; tau; Traumatic Brain Injury
• ISSN: 0269-9052; 1362-301X
• DOI: 10.1080/02699052.2018.1486457

Objectives: We hypothesized that polypathology is more severe in older than younger mice during the acute phase following repetitive mild traumatic brain injury (r-mTBI). Methods: Young and aged male and female mice transgenic for human tau (hTau) were exposed to r-mTBI or a sham procedure. Twenty-four hours post-last injury, mouse brain tissue was immunostained for alterations in astrogliosis, microgliosis, tau pathology, and axonal injury. Results: Quantitative analysis revealed a greater percent distribution of glial fibrillary acid protein and Iba-1 reactivity in the brains of all mice exposed to r-mTBI compared to sham controls. With respect to axonal injury, the number of amyloid precursor protein-positive profiles was increased in young vs aged mice post r-mTBI. An increase in tau immunoreactivity was found in young and aged injured male hTau mice. Conclusions: We report the first evidence in our model that r-mTBI precipitates a complex sequelae of events in aged vs young hTau mice at an acute time point, typified by an increase in phosphorylated tau and astroglisosis, and a diminished microgliosis response and axonal injury in aged mice. These findings suggest differential age-dependent effects in TBI pathobiology.