The mechanism of human neural stem cell secretomes improves neuropathic pain and locomotor function in spinal cord injury rat models: through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities

Abstract

Background: Globally, spinal cord injury (SCI) results in a big burden, including 90% suffering permanent disability, and 60%-69% experiencing neuropathic pain. The main causes are oxidative stress, inflammation, and degeneration. The efficacy of the stem cell secretome is promising, but the role of human neural stem cell (HNSC)secretome in neuropathic pain is unclear. This study evaluated how the mechanism of HNSC-secretome improves neuropathic pain and locomotor function in SCI rat models through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities. Methods: A proper experimental study investigated 15 Rattus norvegicus divided into normal, control, and treatment groups (30 µL HNSC-secretome, intrathecal in the level of T10, three days post-traumatic SCI). Twentyeight days post-injury, specimens were collected, and matrix metalloproteinase (MMP)-9, F2-Isoprostanes, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and brain derived neurotrophic factor (BDNF) were analyzed. Locomotor recovery was evaluated via Basso, Beattie, and Bresnahan scores. Neuropathic pain was evaluated using the Rat Grimace Scale. Results: The HNSC-secretome could improve locomotor recovery and neuropathic pain, decrease F2-Isoprostane (antioxidant), decrease MMP-9 and TNF-α (anti-inflammatory), as well as modulate TGF-β and BDNF (neurotrophic factor). Moreover, HNSC-secretomes maintain the extracellular matrix of SCI by reducing the matrix degradation effect of MMP-9 and increasing the collagen formation effect of TGF-β as a resistor of glial scar formation. Conclusions: The present study demonstrated the mechanism of HNSC-secretome in improving neuropathic pain and locomotor function in SCI through antioxidant, anti-inflammatory, anti-matrix degradation, and neurotrophic activities.

Pramipexole has a neuroprotective effect in spinal cord injury and upregulates D2 receptor expression in the injured spinal cord tissue in rats

“…Spinal cord injury is a devastating condition characterized by two distinct stages: primary and secondary injury ( Semita et al, 2023 ). The primary injury is typically irreversible ( Anwar, Al Shehabi & Eid, 2016 ) and involves the initial mechanical damage to the spinal cord, often caused by trauma.…”

“…Spinal cord injury (SCI) is a prevalent clinical disorder that causes persistent neurological deficits, including paraplegia and neuropathic pain, imposing substantial challenges for patients and their families ( Semita et al, 2023 ). The high incidence, disability rate, and treatment costs associated with SCI place considerable economic burdens on their families and society ( Lo, Chan & Flynn, 2021 ).…”

Possible Mechanisms of Oxidative Stress-Induced Skin Cellular Senescence, Inflammation, and Cancer and the Therapeutic Potential of Plant Polyphenols

“…Studies have investigated the role of curcumin in oxidative stress-induced skin cellular senescence. UV irradiation and hydrogen peroxide stimulation can induce oxidative stress in human immortalized epidermal keratinocytes (HaCat) and HDFs, as evidenced through elevated levels of ROS and malondialdehyde (MDA), decreased antioxidant enzyme activity, DNA damage, protein carbonylation, and apoptosis [ 223 , 224 , 225 , 226 ]. Curcumin not only reduces the aforementioned oxidative damage, but also activates TGF-β and Nrf2 signaling pathways, enhances collagen production and antioxidant enzyme expression, and decreases MMP-1 and MMP-3 levels [ 146 , 223 , 224 , 227 ].…”