The Neuroprotective Mechanism of Spinal Cord Stimulation in Spinal Cord Ischemia/Reperfusion Injury.
Akt
GSK-3β
STAT3
spinal cord ischemia/reperfusion injury
spinal cord stimulation
Journal
Neuromodulation : journal of the International Neuromodulation Society
ISSN: 1525-1403
Titre abrégé: Neuromodulation
Pays: United States
ID NLM: 9804159
Informations de publication
Date de publication:
Jan 2021
Jan 2021
Historique:
received:
10
08
2019
revised:
02
12
2019
accepted:
02
01
2020
pubmed:
3
3
2020
medline:
19
8
2021
entrez:
2
3
2020
Statut:
ppublish
Résumé
Spinal cord ischemia/reperfusion (I/R) injury following thoracoabdominal aneurysm surgery can lead to severe lower limb neurologic defect. The preliminary result of our study suggested that spinal cord stimulation (SCS) postconditioning effectively protected spinal cord from I/R injury on rabbits. But the mechanism is unknown. In this study, we further investigated the mechanism of SCS postconditioning. New Zealand white rabbits were randomly divided into sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group (n = 24/group). Transient spinal cord ischemia was induced by infrarenal aortic balloon occlusion and performed on all rabbits except rabbits of sham group. Rabbits of I/R group received no further intervention. Rabbits of I/R + 2 Hz SCS and I/R + 50 Hz SCS group received 2 Hz or 50 Hz SCS for 30 min at the onset of reperfusion and then daily. The expression of Akt (serine-threonine kinase)/p-Akt, STAT3 (signal transducer and activator of transcription 3)/p-STAT3 and GSK-3β (glycogen synthase kinase)/p-GSK-3β of spinal cord were measured by Western blot analysis at 8 h, 1 day, 3 day, and 7 day of reperfusion. The Akt expressions of sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points, while the p-Akt expression of I/R + 2 Hz SCS group was significantly higher than that of I/R group and sham group at all prescribed time points; The STAT3 and p-STAT3 expression of I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points except that at 1day of reperfusion the p-STAT3 expression of I/R + 50 Hz SCS group was significantly lower than I/R group. The GSK-3β and p-GSK-3β expressions of I/R, I/R + 2 Hz SCS and I/R + 50 Hz SCS group were not significantly different at all prescribed time points. The neuroprotective effect of 2 Hz SCS postconditioning in spinal cord I/R injury is related to Akt activation but not regulation of STAT3 and GSK-3β phosphorylation.
Sections du résumé
BACKGROUND
BACKGROUND
Spinal cord ischemia/reperfusion (I/R) injury following thoracoabdominal aneurysm surgery can lead to severe lower limb neurologic defect. The preliminary result of our study suggested that spinal cord stimulation (SCS) postconditioning effectively protected spinal cord from I/R injury on rabbits. But the mechanism is unknown. In this study, we further investigated the mechanism of SCS postconditioning.
METHOD
METHODS
New Zealand white rabbits were randomly divided into sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group (n = 24/group). Transient spinal cord ischemia was induced by infrarenal aortic balloon occlusion and performed on all rabbits except rabbits of sham group. Rabbits of I/R group received no further intervention. Rabbits of I/R + 2 Hz SCS and I/R + 50 Hz SCS group received 2 Hz or 50 Hz SCS for 30 min at the onset of reperfusion and then daily. The expression of Akt (serine-threonine kinase)/p-Akt, STAT3 (signal transducer and activator of transcription 3)/p-STAT3 and GSK-3β (glycogen synthase kinase)/p-GSK-3β of spinal cord were measured by Western blot analysis at 8 h, 1 day, 3 day, and 7 day of reperfusion.
RESULT
RESULTS
The Akt expressions of sham, I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points, while the p-Akt expression of I/R + 2 Hz SCS group was significantly higher than that of I/R group and sham group at all prescribed time points; The STAT3 and p-STAT3 expression of I/R, I/R + 2 Hz SCS, and I/R + 50 Hz SCS group were not significantly different at all prescribed time points except that at 1day of reperfusion the p-STAT3 expression of I/R + 50 Hz SCS group was significantly lower than I/R group. The GSK-3β and p-GSK-3β expressions of I/R, I/R + 2 Hz SCS and I/R + 50 Hz SCS group were not significantly different at all prescribed time points.
CONCLUSION
CONCLUSIONS
The neuroprotective effect of 2 Hz SCS postconditioning in spinal cord I/R injury is related to Akt activation but not regulation of STAT3 and GSK-3β phosphorylation.
Identifiants
pubmed: 32114698
doi: 10.1111/ner.13113
pii: S1094-7159(21)00133-1
doi:
Substances chimiques
Glycogen Synthase Kinase 3
EC 2.7.11.26
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
43-48Subventions
Organisme : Beijing Natural Science Foundation
ID : 7152046
Organisme : National Science and Technology support program of China
ID : 2015BAI12B03
Informations de copyright
© 2020 International Neuromodulation Society.
Références
Le Maire SA, Miller CC, Conklin LD et al. Estimating group mortality and paraplegia rates after thoracoabdominal aortic aneurysm repair. Ann Thorac Surg 2003;75:508-513.
Conrad MF, Crawford RS, Davison JK et al. Thoracoabdominal aneurysm repair: A 20-year perspective. Ann Thorac Surg 2007;83:S856-S861.
Coselli JS, Lemaire SA, Preventza O et al. Outcomes of 3309 thoracoabdominal aortic aneurysm repairs. J Thorac Carsiovasc Surg 2016;151:1323-1338.
Kakinohana M, Harada H, Mishima Y, Kano T, Sugahara K. Neuroprotective effect of epidural electrical stimulation against ischemia spinal cord injury in rats. Anesthesiology 2005;103:84-92.
Li HX, Dong XH, Jin M, Cheng WP. The protective effect of spinal cord stimulation postconditioning against spinal cord ischemia/reperfusion injury in rabbits. Neuromodulation 2018;21:448-456.
Baba T, Kameda M, Yasuhara T et al. Electrical stimulation of the cerebral cortex exerts antiapoptotic, angiogenic, and anti-inflammatory effects in ischemic stroke rats through phosphoinositide 3-kinase/Akt signaling pathway. Stroke 2009;40:598-605.
Liang ZX, Wu GL, Fan CX et al. The emerging role of signal transducer and activator of transcription3 in cerebral ischemic and hemorrhagic stroke. Prog Neurobiol 2016;137:1-16.
Rana AK, Singh D. Targeting glycogen synthase kinase-3 for oxidative stress and neuroinflammation: Opportunities, challenges and future directions for cerebral stroke management. Neuropharmacology 2018;139:124-136.
Saraswati AP, Hussaini SMA, Krishna NH, Babu BN, Kamal A. Glycogen synthase kinase-3 and its inhibitors: Potential target for various therapeutic conditions. Eur J Med Chem 2018;144:843-858.
Mackey ME, Wu YJ, Hu R et al. Cell death suggestive of apoptosis after spinal cord ischemia in rabbits. Stroke 1997;28:2012-2017.
Sakurai M, Hayashi T, Abe K, Sadahiro M, Tabayashi K. Delayed and selective motor neuron death after transient spinal cord ischemia: A role of apoptosis? J Thoracic Cardiovascular Surgery 1998;115:1310-1315.
Noshita N, Lewe'n A, Sugawara T, Chan PH. Evidence of phosphorylation of Akt and neuronal survival after transient focal cerebral ischemia in mice. J Cereb Blood Flow Metab 2001;21:1442-1450.
Yu F, Sugawara T, Maier CM, Hsieh LB, Chan PH. Akt/Bad signaling and motor neuron survival after spinal cord injury. Neurobiol Dis 2005;20:491-499.
Du K, Montminy M. CREB is a regulatory target for the protein kinase Akt/PKB. J Biol Chem 1998;273:32377-32379.
Kane LP, Shapiro VS, Stokoe D, Weiss A. Induction of NF-kB by the Akt/PKB kinase. Curr Biol 1999;9:601-604.
Brunet A, Datta SR, Greenberg ME. Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 2001;11:297-305.
Cardone MH, Roy N, Stennicke HR et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 1998;282:1318-1321.
Tu XK, Yang WZ, Chen JP et al. Repetitive ischemic preconditioning attenuates inflammatory reaction and brain damage after focal cerebral ischemia in rats: Involvement of PI3K/Akt and ERK1/2 signaling pathway. J Mol Neurosci 2015;55:912-922.
Jiang XJ, Ai C, Shi EY, Nakajima Y, Ma H. Neuroprotection against spinal cord ischemia-reperfusion injury induced by different ischemic postconditioning methods: Roles of phosphatidylinositol 3-kinase-Akt and extracellular signal-regulated kinase. Anesthesiology 2009;111:1197-1205.
Liu SY, Yang YW, Jin M et al. Xenon-delayed postconditioning attenuates spinal cord ischemia/reperfusion injury through activation AKT and ERK signaling pathways in rats. J Neurol Sci 2016;368:277-284.
Satriotomo I, Bowen KK, Vemuganti R. JAK2 and STAT3 activation contributes to neuronal damage following transient focal cerebral ischemia. J Neurochem 2006;98:1353-1368.
Lei C, Deng J, Wang B et al. Reactive oxygen species scavenger inhibits STAT3 activation after transient focal cerebral ischemia-reperfusion injury in rats. Anesth Analg 2011;113:153-159.
Cheng Z, Li L, Mo X et al. Non-invasive remote limb ischemic postconditioning protects rats against focal cerebral ischemia by upregulating STAT3 and reducing apoptosis. Int J Mol Med 2014;34:957-966.
Kim HC, Kim E, Bae JI et al. Sevoflurane postconditioning reduces apoptosis by activating the JAK-STAT pathway after transient global cerebral ischemia in rats. J Neurosurg Anesthesiol 2017;29:37-45.
Yamanaka K, Eldeiry M, Aftab M et al. Pretreatment with diazoxide attenuates spinal cord ischemia-reperfusion injury through signaling transducer and activator of transcription 3 pathway. Ann Thorac Surg 2019;107:733-739.
Li YX, Zhu J, Liu YL et al. Glycogen synthase kinase 3β influences injury following cerebral ischemia/reperfusion in rats. Int J Biol Sci 2016;12:518-531.
Wang W, Li MC, Wang YF et al. GSK-3β as a target for protection against transient cerebral ischemia. Int J Med Sci 2017;14:333-339.