Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury

• Published in: Experimental neurology 2018-02, Vol.300, p.167-178
• Main Authors: Pischiutta, Francesca, Micotti, Edoardo, Hay, Jennifer R., Marongiu, Ines, Sammali, Eliana, Tolomeo, Daniele, Vegliante, Gloria, Stocchetti, Nino, Forloni, Gianluigi, De Simoni, Maria-Grazia, Stewart, William, Zanier, Elisa R.
• Format: Article
• Language: English
• Subjects: Animals; Brain Injuries, Traumatic - complications; Brain Injuries, Traumatic - diagnostic imaging; Brain Injuries, Traumatic - pathology; Diffusion Tensor Imaging - trends; Disease Progression; Inflammation; Long-term outcome; Magnetic Resonance Imaging - trends; Male; Maze Learning - physiology; Mice; Mice, Inbred C57BL; Neurodegeneration; Neuroimaging; Severity of Illness Index; Traumatic brain injury; White Matter - diagnostic imaging; White Matter - pathology; White matter damage
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2017.11.003

There is increasing recognition that traumatic brain injury (TBI) may initiate long-term neurodegenerative processes, particularly chronic traumatic encephalopathy. However, insight into the mechanisms transforming an initial biomechanical injury into a neurodegenerative process remain elusive, partly as a consequence of the paucity of informative pre-clinical models. This study shows the functional, whole brain imaging and neuropathological consequences at up to one year survival from single severe TBI by controlled cortical impact in mice. TBI mice displayed persistent sensorimotor and cognitive deficits. Longitudinal T2 weighted magnetic resonance imaging (MRI) showed progressive ipsilateral (il) cortical, hippocampal and striatal volume loss, with diffusion tensor imaging demonstrating decreased fractional anisotropy (FA) at up to one year in the il-corpus callosum (CC: −30%) and external capsule (EC: −21%). Parallel neuropathological studies indicated reduction in neuronal density, with evidence of microgliosis and astrogliosis in the il-cortex, with further evidence of microgliosis and astrogliosis in the il-thalamus. One year after TBI there was also a decrease in FA in the contralateral (cl) CC (−17%) and EC (−13%), corresponding to histopathological evidence of white matter loss (cl-CC: −68%; cl-EC: −30%) associated with ongoing microgliosis and astrogliosis. These findings indicate that a single severe TBI induces bilateral, long-term and progressive neuropathology at up to one year after injury. These observations support this model as a suitable platform for exploring the mechanistic link between acute brain injury and late and persistent neurodegeneration. [Display omitted] •Longitudinal effects of single severe TBI by controlled cortical impact were examined.•TBI triggers an evolving damage that at chronic stages spreads to the contralateral hemisphere.•Contralateral pathology at one year post TBI, shows a prominent involvement of white matter with ongoing neuroinflammation.•Findings support the model for studies interrogating the link between biomechanical impact and late neurodegeneration.