Calderón-Estrella Francisco, Franco-Bourland Rebecca E, Rios Camilo, de Jesús-Nicolás Diana, Pineda Benjamín, Méndez-Armenta Marisela, Mata-Bermúdez Alfonso, Diaz-Ruiz Araceli
Posgrado en Ciencias Biológicas de la Facultad de Ciencias, Universidad Nacional Autónoma de México, Ciudad de México, 04369, Mexico.
Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de México, 14389, Mexico.
Heliyon. 2023 Mar 20;9(4):e14687. doi: 10.1016/j.heliyon.2023.e14687. eCollection 2023 Apr.
Failure of therapeutic strategies for the management and recovery from traumatic spinal cord injury (SCI) is a serious concern. Dapsone (DDS) has been reported as a neuroprotective drug after SCI, although the phase after SC damage (acute or chronic) of its major impact on functional recovery has yet to be defined. Here, we evaluated DDS acute-phase anti-inflammatory effects and their impact on early functional recovery, one week after moderate SCI, and late functional recovery, 7 weeks thereafter. Female Wistar rats were randomly assigned to each of five experimental groups: sham group; four groups of rats with SCI, treated with DDS (0, 12.5, 25.0, and 37.5 mg/kg ip), starting 3 h after injury. Plasma levels of GRO/KC, and the number of neutrophils and macrophages in cell suspensions from tissue taken at the site of injury were measured as inflammation biomarkers. Hindlimb motor function of injured rats given DDS 12.5 and 25.0 mg/kg daily for 8 weeks was evaluated on the BBB open-field ordinal scale. Six hours after injury all DDS doses decreased GRO/KC plasma levels; 24 h after injury, neutrophil numbers decreased with DDS doses of 25.0 and 37.5 mg/kg; macrophage numbers decreased only at the 37.5 mg/kg dose. In the acute phase, functional recovery was dose-dependent. Final recovery scores were 57.5 and 106.2% above the DDS-vehicle treated control group, respectively. In conclusion, the acute phase dose-dependent anti-inflammatory effects of DDS impacted early motor function recovery affecting final recovery at the end of the study.
创伤性脊髓损伤（SCI）治疗和恢复策略的失败是一个严重问题。据报道，氨苯砜（DDS）是SCI后的一种神经保护药物，但其对功能恢复产生主要影响的脊髓损伤后阶段（急性或慢性）尚未明确。在此，我们评估了DDS在中度SCI后一周的急性期抗炎作用及其对早期功能恢复的影响，以及此后7周的晚期功能恢复情况。将雌性Wistar大鼠随机分为五个实验组：假手术组；四组SCI大鼠，在损伤后3小时开始腹腔注射DDS（0、12.5、25.0和37.5mg/kg）。测量血浆中GRO/KC水平，以及损伤部位组织细胞悬液中的中性粒细胞和巨噬细胞数量作为炎症生物标志物。对每天给予12.5和25.0mg/kg DDS持续8周的损伤大鼠的后肢运动功能，采用BBB旷场序数评分法进行评估。损伤后6小时，所有DDS剂量均降低了血浆GRO/KC水平；损伤后24小时，25.0和37.5mg/kg DDS剂量组的中性粒细胞数量减少；仅37.5mg/kg剂量组的巨噬细胞数量减少。在急性期，功能恢复呈剂量依赖性。最终恢复评分分别比DDS载体处理的对照组高出57.5%和106.2%。总之，DDS在急性期的剂量依赖性抗炎作用影响了早期运动功能恢复，进而影响了研究结束时的最终恢复情况。
