RESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating late onset neurodegenerative disorder that is characterised by the progressive loss of upper and lower motor neurons. The mechanisms underlying ALS pathogenesis are unclear; however, there is emerging evidence the innate immune system, including components of the toll-like receptor (TLR) system, may drive disease progression. For example, toll-like receptor 4 (TLR4) antagonism in a spontaneous 'wobbler mouse' model of ALS increased motor function, associated with a decrease in microglial activation. This study therefore aimed to extend from these findings and determine the expression and function of TLR4 signalling in hSOD1(G93A) mice, the most widely established preclinical model of ALS. FINDINGS: TLR4 and one of its major endogenous ligands, high-mobility group box 1 (HMGB1), were increased during disease progression in hSOD1(G93A) mice, with TLR4 and HMGB1 expressed by activated microglia and astrocytes. hSOD1(G93A) mice lacking TLR4 showed transient improvements in hind-limb grip strength and significantly extended survival when compared to TLR4-sufficient hSOD1(G93A) mice. CONCLUSION: These results suggest that enhanced glial TLR4 signalling during disease progression contributes to end-stage ALS pathology in hSOD1(G93A) mice.
Asunto(s)
Esclerosis Amiotrófica Lateral/genética , Esclerosis Amiotrófica Lateral/mortalidad , Superóxido Dismutasa/genética , Receptor Toll-Like 3/deficiencia , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/fisiopatología , Animales , Peso Corporal/genética , Proteínas de Unión al Calcio/metabolismo , Colina O-Acetiltransferasa/metabolismo , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/genética , Proteína Ácida Fibrilar de la Glía/genética , Proteína Ácida Fibrilar de la Glía/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Miembro Posterior/fisiopatología , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas de Microfilamentos/metabolismo , Fuerza Muscular/genética , ARN Mensajero/metabolismo , Médula Espinal/metabolismo , Análisis de Supervivencia , Receptor Toll-Like 3/genéticaRESUMEN
BACKGROUND: Pole dancing is a physically demanding sport which combines acrobatics and aerial stunts which could potentially lead to be severely debilitating injuries. However, there is a paucity of medical research data on the injuries that can be sustained. The objective of this study aimed to determine the prevalence of pole injuries, the severity of injuries that can be sustained from this activity, and to help to determine safety protocols. The results will also aid physiotherapists in prescribing exercises when treating pole dancers. METHODS: Cross sectional data was collected from an online web-based survey via social media platforms over 2 weeks in March in 2019. RESULTS: The most commonly reported injuries were shoulder related (54.5%) injuries, wrist (34.2%) and back (24.7%) injuries. 75.5% of injuries were acutely sustained. Pole dancers who were 40 and above were 3.7 times more likely (95% CI: 1.14 to 11.76, P=0.030) to need more than 3 months to recover from their pole injuries than those who were aged from 19 to 29 years. Participants with 3 to 6 years of pole sport experience were at 3.9 times (95% CI: 1.24, 12.39, P=0.020) higher risk for moderate/severe injuries, than those who had less experience. CONCLUSIONS: Our study shows that the most common injuries are sustained in the shoulder and wrist. We also found a relation with age and experience. More studies on this sport is needed to create injury prevention programs and safety protocols.