Amlodipine Improves Spinal Cord Injury Repair by Inhibiting Motoneuronal Apoptosis Through Autophagy Upregulation

Abstract

Study Design. The effect of amlodipine (AM) on spinal cord injury (SCI) and autophagy was researched by establishing ventral spinal cord cells (VSC4.1) oxygen and glucose deprivation model and SCI mice model. Objective. To determine the neuroprotective effects of AM by upregulating autophagy during SCI repair. Summary of Background Data. AM, an antihypertensive medication, has been shown in several studies to inhibit neuronal apoptosis and exert neuroprotective effects in various central nervous system diseases. However, its effects on SCI are unexplored. Autophagy could inhibit cell apoptosis, which has been shown to promote SCI repair. However, the role of AM in autophagy remains unclear. Methods. We examined the relationship between AM, apoptosis, and autophagy in ventral spinal cord cells and the injured spinal cords of C57BL/6 female mice respectively, following histological, behavioral, microscopic, immunofluorescence, and western blotting analyses. Results. We found that AM could inhibit motor neuronal apoptosis in vitro. Furthermore, AM promoted locomotor recovery by upregulating autophagy and alleviating apoptosis, neuronal loss, and spinal cord damage after SCI. Conclusion. AM inhibited motoneuronal apoptosis by upregulating autophagy to improve SCI recovery.

Upregulation of UBR1 m6A Methylation by METTL14 Inhibits Autophagy in Spinal Cord Injury

“…Autophagy dysfunction is implicated in the pathogenesis of major human diseases including cancers and neurodegenerative disorders ( Klionsky et al, 2021 ). In SCI, the repair of autophagic flux or activation of autophagy reduces neuronal inflammation, apoptosis, and pyroptosis ( Rong et al, 2019 ; Zhou et al, 2020 ; Wu et al, 2021 ; Huang et al, 2022 ). UBR1 also has the potential to regulate autophagy and mitophagy ( Yamano and Youle, 2013 ; B.B.…”

Calcium/P53/Ninjurin 1 Signaling Mediates Plasma Membrane Rupture of Acinar Cells in Severe Acute Pancreatitis

“…Twenty wild-type C57BL/6 mice were randomly divided into four groups, including a control group, STC group, STC + NINJ1 26-37 (3 mg/kg) group, and STC + NINJ1 26-37 (6 mg/kg) group [32]. The other twenty wild-type C57BL/6 mice were randomly divided into four groups, including a control group, STC group, STC + AML (3 mg/kg) group, and STC + AML (6 mg/kg) group [33,34].…”

“…The solution was solubilized under ultrasound and used immediately after preparation. Two days before and after retrograde injection of the pancreatobiliary duct, a daily dose of 3 mg/kg (50 µL) and 6 mg/kg (100 µL) of NINJ1 [26][27][28][29][30][31][32][33][34][35][36][37] or AML was administrated to different groups through intraperitoneal injection. For the control group and the STC group, the same volume of physiological saline solution was applied (100 µL).…”

Research

“…However, in this interesting animal study from Taizhou (China) , a team have investigated its effects on neuronal death following spinal cord injury. 1 A spinal cord injury was created in a rat model by hemisecting the cord, and these rats were either administered amlodipine or not. A further control group underwent a laminectomy without cord injury.…”

“…Despite these early observations, there has not been any clinical interest and, until recently, the line of basic science investigation had gone relatively cold. However, in this interesting animal study from Taizhou (China), a team have investigated its effects on neuronal death following spinal cord injury 1. A spinal cord injury was created in a rat model by hemisecting the cord, and these rats were either administered amlodipine or not.…”