Traumatic brain injury augments disease pathology in a mouse model of amyotrophic lateral sclerosis and wild type mice (651.11)

Abstract

Traumatic Brain Injury (TBI) is a known risk factor for ALS. The goal of this study is to elucidate the mechanism linking TBI to motor neuron disease, by testing the hypothesis that TBI will accelerate disease progression in an animal model of ALS. We used a well‐characterized mouse model of familial ALS (G93A SOD1) to study the effect of TBI on ALS progression. Mice were subjected to a closed head traumatic brain injury and magnetic resonance imaging (MRI) was used 3 days after injury to characterize structural central nervous system pathology and the severity of brain injury. Histological techniques showed astrocyte infiltration (GFAP) and edema (Nissl) following mild TBI in brain and spinal cord of wildtype (WT) and transgenic mice (TG). Our results indicate that TBI leads to early reductions in grip strength and rotarod performance. Further, muscle denervation is potentiated as is shown via electromyography abnormalities. We have also characterized the effect of TBI on disease related weight loss and overall disease score in G93A mice. Our results are the first to show that TBI, in an animal model of ALS, results in significantly increased muscle denervation and brain and spinal cord pathology.Grant Funding Source: This work is supported by an individual NRSA fellowship grant, 1F31NS080508‐01