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 ; Biobehavioral Research Core, Cedars-Sinai Medical Center , Los Angeles, CA 90048.
eNeuro. 2015 Jul 3;2(3). doi: 10.1523/ENEURO.0059-14.2015. eCollection 2015 May-Jun.
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.
肌萎缩侧索硬化症（ALS）是一种致命的运动神经元疾病，其中上下运动神经元退化，导致发病后 3 至 5 年内肌肉萎缩、瘫痪和死亡。虽然一小部分 ALS 病例与遗传有关，但大多数是散发性的，其病因不明。目前，病因学关联与发病有关，但缺乏机制上的理解。然而，在所有假定的危险因素中，头部创伤已成为引发 ALS 分子级联反应的一致候选因素。在这里，我们检验了这样一个假设，即在 ALS 的 SOD1（G93A）转基因大鼠模型中，创伤性脑损伤（TBI）会导致疾病早期发作和寿命缩短。然而，我们证明，由皮质撞击引起的单次急性局灶性损伤不会影响疾病发作或存活。确定单次急性局灶性脑损伤在 ALS 大鼠模型中几乎没有参与，这增加了对该疾病的现有理解。至关重要的是，将单次局灶性 TBI 与多次轻度损伤区分开来，为科学家和医生提供了一个理由，使他们更加关注重复损伤，以期确定 ALS 的一个致病原因。
