J Neurophysiol. 2019 May 22. doi: 10.1152/jn.00572.2018. [Epub ahead of print]

The Impact of Traumatic Brain Injury on Amyotrophic Lateral Sclerosis - From Bedside to Bench.

Franz CK¹, Joshi D¹, Daley EL², Grant RA³, Dalamagkas K⁴, Leung A¹, Finan JD⁵, Kiskinis E⁶.

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the loss of upper and lower motor neurons (MNs), which manifests clinically as progressive weakness. Although several epidemiological studies have found an association between traumatic brain injury (TBI) and ALS, there is not a consensus on whether TBI is an ALS risk factor. It may be that it can cause ALS in a subset of susceptible patients, based on a history of repetitive mild TBI and genetic predisposition. This cannot be determined based on clinical observational studies alone. Better pre-clinical models are necessary to evaluate the effects of TBI on ALS onset and progression. To date, only a small number of pre-clinical studies have been performed, mainly in the superoxide dismutase 1 (SOD1) transgenic rodents, which, taken together, have mixed results, and notable methodological limitations. The more recent incorporation of additional animal models such as Drosophila flies, as well as patient induced pluripotent stem cells (iPSC)-derived neurons, should facilitate a better understanding of a potential functional interaction between TBI and ALS.