N. K. Dhillon1, G. Barmparas1, N. Cho1, M. Alkaslasi1, M. Marcelino1, P. S. Haro1, E. J. Ley1, G. M. Thomsen1 1Cedars-Sinai Medical Center,Los Angeles, CA, USA
Introduction: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized in part by degeneration of motor neurons in the spinal cord. We recently reported that recurrent traumatic brain injury (rTBI) leads to earlier disease onset in SOD1 rats genetically predisposed to ALS and is associated with sustained motor deficits in wild type (WT) rats. We hypothesized that rTBI in SOD1 ALS rats exacerbates degeneration of spinal cord motor neuron (SCMN) and rTBI in WT rats leads to a similar SCMN degeneration observed in ALS.
Methods: Fourteen WT and eight SOD1 rats were selected for histological analysis from a larger cohort of rats that had undergone either sham or repeat TBI and behavioral assessment. rTBI rats were administered repeat, bilateral, closed skull TBI once a week with a controlled cortical impact device over a 5-week period. Spinal cords were collected from SOD1 rats at disease endpoint and from WT rats at the age of 235 days. Histological analysis of SCMNs was conducted by staining for choline acetyltransferase (ChAT) followed by quantification and cell-size analysis of ChAT+ cells.
Results: At study endpoint, we found that although the total number of ChAT+ spinal motor neuron was significantly decreased in sham and rTBI SOD1 rats, indicative of disease progress, there was no effect of rTBI in either WT or SOD1 rats (Figure). Similarly, the average size of ChAT+ cells was not changed after rTBI indicating that rTBI does not lead to degeneration of SCMNs in either WT or SOD1 rats.
Conclusion: Our results are the first to demonstrate that the overall health of spinal motor neurons is not compromised by repetitive injury to the brain. Spinal motor neurons were not affected by rTBI in SOD1 ALS or WT rats suggesting that the functional deficits that occur are solely due to repeat brain trauma. Importantly, the more rapid deterioration that occurs with rTBI superimposed upon ALS appears to be due to separate mechanisms related to each.
