title: Acute Traumatic Brain Injury Does Not Exacerbate Amyotrophic Lateral Sclerosis in the SOD1 (G93A) Rat Model
abstract: Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease in which upper and lower motor neurons degenerate, leading to muscle atrophy, paralysis, and death within 3 to 5 years of onset. While a small percentage of ALS cases are genetically linked, the majority are sporadic with unknown origin. Currently, etiological links are associated with disease onset without mechanistic understanding. Of all the putative risk factors, however, head trauma has emerged as a consistent candidate for initiating the molecular cascades of ALS. Here, we test the hypothesis that traumatic brain injury (TBI) in the SOD1 (G93A) transgenic rat model of ALS leads to early disease onset and shortened lifespan. We demonstrate, however, that a one-time acute focal injury caused by controlled cortical impact does not affect disease onset or survival. Establishing the negligible involvement of a single acute focal brain injury in an ALS rat model increases the current understanding of the disease. Critically, untangling a single focal TBI from multiple mild injuries provides a rationale for scientists and physicians to increase focus on repeat injuries to hopefully pinpoint a contributing cause of ALS.
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Gretchen M
authors.initials: GM
authors.lastname: Thomsen
authors.affiliation: Department of Biomedical Sciences, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ; Biobehavioral Research Core, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Vit
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lamb
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Gowing
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Oksana
authors.initials: O
authors.lastname: Shelest
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Mor
authors.initials: M
authors.lastname: Alkaslasi
authors.affiliation: Department of Surgery, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Ley
authors.affiliation: Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center , Los Angeles, CA 90048 ; Department of Biomedical Sciences, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
authors.forename: Clive N
authors.initials: CN
authors.lastname: Svendsen
keywords: ALS; SOD1; TBI; amyotrophic lateral sclerosis; neurodegeneration; traumatic brain injury