Abstract
In the present study, we searched for possible candidates that can prevent ischemic damage in the rabbit spinal cord. For this study, we used two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, in sham- and ischemia-operated animals. As the level of protein disulfide-isomerase A3 (PDIA3) significantly decreased 3 h after ischemia/reperfusion, we further investigated its possible role against ischemic damage using an in vitro spinal cord cell line and in vivo spinal cord ischemic model. The administration of Tat-PDIA3 significantly reduced the hydrogen peroxide-induced formation of reactive oxygen species and cell death, based on terminal deoxynucleotidyl transferase-mediated biotinylated dUTP nick end labeling and a colorimetric WST-1 assay. Further, Tat-PDIA3 significantly ameliorated the ischemia-induced deficits in motor function, based on Tarlov’s criteria, 24–72 h after ischemia/reperfusion, as well as the degeneration of motor neurons in the ventral horn 72 h after ischemia/reperfusion. Tat-PDIA3 administration also reduced the ischemia-induced activation of microglia and lipid peroxidation in the motor neurons 72 h after ischemia/reperfusion. PDIA3 also potentially ameliorated the ischemia-induced increase in oxidative markers in serum and decreased the activity of Cu,Zn-superoxide dismutase, Mn-superoxide dismutase, and glutathione peroxidase in spinal cord homogenates, 24 h and 72 h after ischemia/reperfusion. These results suggest that Tat-PDIA3 could be used to protect spinal cord neurons from ischemic damage, due to its modulatory action on the oxidative/anti-oxidative balance. Tat-PDIA3 could be applicable to protects neurons from the ischemic damage induced by thoracoabdominal aorta obstruction.
Highlights
Spinal cord ischemia and reperfusion injury are devastating complications, which follow surgeries implicating the descending and thoracoabdominal aorta, and have an incidence that ranges from 2.7 to 28%.1,2 As neuronal death induced by an abdominal aorta occlusion can be modeled using segmental blood supply to the spinal cord, this is used in animal models to investigate the mechanism of cell death in spinal cord ischemia.[3]
Spinal cord ischemia can result in neuronal damage, inducing immediate or delayed paraplegia as a major complication of surgery for an aorta in the thoracic and abdominal regions
We narrowed this list to seven proteins, excluded predicted and unidentifiable proteins, and chose protein disulfide-isomerase A3 (PDIA3) for further analysis since it has thioredoxin-like domains, which showed neuroprotective effects against ischemic damage in the gerbil hippocampus.[13]
Summary
Spinal cord ischemia and reperfusion injury are devastating complications, which follow surgeries implicating the descending and thoracoabdominal aorta, and have an incidence that ranges from 2.7 to 28%.1,2 As neuronal death induced by an abdominal aorta occlusion can be modeled using segmental blood supply to the spinal cord, this is used in animal models to investigate the mechanism of cell death in spinal cord ischemia.[3]. As neuronal death induced by an abdominal aorta occlusion can be modeled using segmental blood supply to the spinal cord, this is used in animal models to investigate the mechanism of cell death in spinal cord ischemia.[3]. The transient occlusion of the abdominal aorta underneath the renal artery depletes the glucose and oxygen supply to the spinal cord and causes neuronal degeneration in the dorsal and ventral horn of spinal cord.[3,4,5] Ischemia reperfusion activates a series of processes in the neurons of the spinal cord, including glutamatemediated excitotoxicity, inflammation, and oxidative stress. Thereafter, we investigated the possibility of using differentially expressed proteins as therapeutic targets in spinal cord ischemia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
