Journal of neurotrauma
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Journal of neurotrauma · May 2022
Exosomes secreted by hypoxia-preconditioned adipose-derived mesenchymal stem cells reduce neuronal apoptosis in rats with spinal cord injury.
Neuronal death is the main cause of nerve function impairment after spinal cord injury (SCI). Exosome-based therapy has become a novel strategy for tissue injury repair. We designed a method to treat SCI using exosomes secreted by adipose tissue-derived stromal cells (ADSCs) under hypoxic conditions. ⋯ Through real-time polymerase chain reaction, dual luciferase reporter assays and signaling pathway chip analysis, we determined that miR-499a-5p regulates the JNK3/c-jun-apoptotic signaling pathway by targeting JNK3. Further, we verified the expression of the key proteins in the JNK3/c-jun-apoptotic signaling pathway by immunofluorescence and Western blotting. These results support the hypothesis that Hypo-exo can reduce neuronal apoptosis after SCI and may provide new methods to treat SCI.
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Journal of neurotrauma · May 2022
Suppression of TRPM7 by carvacrol protects against injured spinal cord by inhibiting blood-spinal cord barrier disruption.
When the blood-spinal cord barrier (BSCB) is disrupted after a spinal cord injury (SCI), several pathophysiological cascades occur, including inflammation and apoptotic cell death of neurons and oligodendrocytes, resulting in permanent neurological deficits. Transient receptor potential melastatin 7 (TRPM7) is involved in the pathological processes in many neuronal diseases, including traumatic brain injury, amyotrophic lateral sclerosis, parkinsonism dementia, and Alzheimer's disease. Further, carvacrol (CAR), a TRPM7 inhibitor, is known to protect against SCI by reducing oxidative stress and inhibiting the endothelial nitric oxide synthase pathway. ⋯ Additionally, CAR treatment suppressed BSCB disruption by inhibiting the loss of tight junction (TJ) proteins and preserved TJ integrity. CAR also reduced apoptotic cell death and improved functional recovery after SCI by preventing BSCB disruption caused by blood infiltration and inflammatory responses. Based on these findings, we propose that blocking the TRPM7 channel can inhibit the destruction of the BSCB and it is a potential target in therapeutic drug development for use in SCI.