Pretreatment With Diazoxide Attenuates Spinal Cord Ischemia-Reperfusion Injury Through Signaling Transducer and Activator of Transcription 3 Pathway

Yamanaka, Katsuhiro; Eldeiry, Mohamed; Aftab, Muhammad; Ryan, Thomas J.; Roda, Gavriel F.; Meng, Xianzhong; Weyant, Michael J.; Cleveland, Joseph C.; Fullerton, David A.; Reece, T. Brett

doi:10.1016/j.athoracsur.2018.09.031

Cited by 10 publications

(7 citation statements)

References 34 publications

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“…Spinal fracture with spinal cord injury causes motor, sensory, sphincter, and autonomic nervous system disorders below the injury level. The patients' respiration, circulation, metabolism, and body temperature regulation are adversely influenced, and quality of life is severely affected [ 11 , 12 ].…”

Section: Discussionmentioning

confidence: 99%

Outcomes of Patients with Cervical Spinal Cord Injury Treated by Surgery and Their Prognostic Factors

Song

Jin

et al. 2022

Applied Bionics and Biomechanics

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Objective. To investigate the outcomes of patients with cervical spinal cord injury treated by surgery and their prognostic factors. Methods. We retrospectively analyzed 139 patients with cervical spinal cord injury treated by surgery at our hospital, who were admitted between January 2017 and December 2018. Depending on the Barthel index at last follow-up, the patients were divided into the recovery group ( n = 60 , Barthel index > 45 ) and the nonrecovery group ( n = 79 , Barthel index ≤ 45 ). General information of patients in the two groups was compared. The significant factors were further introduced into the logistic regression model. The poor prognostic factors of cervical spinal cord injury treated by surgery were analyzed, and specific nursing measures were taken. Results. There were significant differences in the duration of injury before admission, duration of injury before surgery, transportation and protection before admission, spinal canal invasion rate, and hormonal therapy within 8 h after injury between the patients achieving good postoperative recovery and those not ( P < 0.05 ). Logistic regression analysis showed that all the factors above were prognostic factors for cervical spinal cord injury treated surgically. Conclusion. The duration of injury before admission, duration of injury before surgery, transportation and protection before admission, spinal canal invasion rate, and hormonal therapy within 8 h after injury were prognostic factors of patients with cervical spinal cord injury treated by surgery. The following factors should be considered for favorable outcomes: spinal protection during transportation to hospital, timely hormonal shock therapy to delay injury progression, and timely surgery to relieve pain. The spine is composed of cervical, thoracic, lumbar, sacral, and caudal vertebrae.

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Section: Discussionmentioning

confidence: 99%

Outcomes of Patients with Cervical Spinal Cord Injury Treated by Surgery and Their Prognostic Factors

Song

Jin

et al. 2022

Applied Bionics and Biomechanics

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“…Both nicorandil and cromakalim were also effective against cerebral IRI in diabetic rats, lowering caspase-3 levels, with the first also significantly reducing cerebral infarct volume [244]. Also, a drug clinically used to treat hypoglycemia, diazoxide, has been yielding promising results regarding ischemic tolerance and IRI protection in the heart, pancreas, smooth muscle, endothelium [245], intestine, liver [248], and spinal cord [246]. Although this agent acts through its classical mechanism as a selective mK ATP agonist, pretreatment with diazoxide may also engage the RISK and SAFE pathways by upregulating both the expression of the beta common receptor subunit of the erythropoietin receptor [247] and the STAT3 mechanism, respectively [246].…”

Section: Therapeutics: the Pharmacological Approachmentioning

confidence: 99%

“…Also, a drug clinically used to treat hypoglycemia, diazoxide, has been yielding promising results regarding ischemic tolerance and IRI protection in the heart, pancreas, smooth muscle, endothelium [245], intestine, liver [248], and spinal cord [246]. Although this agent acts through its classical mechanism as a selective mK ATP agonist, pretreatment with diazoxide may also engage the RISK and SAFE pathways by upregulating both the expression of the beta common receptor subunit of the erythropoietin receptor [247] and the STAT3 mechanism, respectively [246]. Literature reports in the literature show significant pharmacologic overlap between respiratory complex II inhibitors and mK ATP channel agonists: malonate [324] and atpenin A5 [325] are able to activate the mK ATP channel and offer cardioprotection in rats at reperfusion.…”

Section: Therapeutics: the Pharmacological Approachmentioning

confidence: 99%

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

Soares

Losada

Jordani

et al. 2019

IJMS

223

180

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Ischemia/reperfusion injury (IRI) permeates a variety of diseases and is a ubiquitous concern in every transplantation proceeding, from whole organs to modest grafts. Given its significance, efforts to evade the damaging effects of both ischemia and reperfusion are abundant in the literature and they consist of several strategies, such as applying pre-ischemic conditioning protocols, improving protection from preservation solutions, thus providing extended cold ischemia time and so on. In this review, we describe many of the latest pharmacological approaches that have been proven effective against IRI, while also revisiting well-established concepts and presenting recent pathophysiological findings in this ever-expanding field. A plethora of promising protocols has emerged in the last few years. They have been showing exciting results regarding protection against IRI by employing drugs that engage several strategies, such as modulating cell-surviving pathways, evading oxidative damage, physically protecting cell membrane integrity, and enhancing cell energetics.

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“…In global cerebral ischemia, Kim and colleagues (24) found that sevoflurane postconditioning reduced cell apoptosis and increased p-JAK and p-STAT expression of the brain, while JAK2 inhibitor reversed the anti-apoptosis effects of sevoflurane, which suggested that sevoflurane postconditioning reduces apoptosis by activating the JAK/STAT3 pathway. In addition, Yamanaka et al (25) demonstrated in their study that diazoxide attenuated spinal cord ischemia/reperfusion injury through activation of STAT3. In our study, except for 1 day of reperfusion when the p-STAT3 expression of I/R + 50 Hz SCS group was significantly lower than that of the I/R group, the p-STAT3 expressions of I/R + 2 Hz SCS, I/R + 50 Hz SCS groups were not significantly different from that of the I/R group at other prescribed time points, which suggests that the neuroprotective effects of 2 Hz SCS postconditioning in spinal cord I/R injury do not involve regulation of STAT3 activation or JAK2/STAT3 pathway.…”

Section: Discussionmentioning

confidence: 99%

The Neuroprotective Mechanism of Spinal Cord Stimulation in Spinal Cord Ischemia/Reperfusion Injury

Dong

Yang

et al. 2021

Neuromodulation: Technology at the Neural Interface

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Pretreatment With Diazoxide Attenuates Spinal Cord Ischemia-Reperfusion Injury Through Signaling Transducer and Activator of Transcription 3 Pathway

Cited by 10 publications

References 34 publications

Outcomes of Patients with Cervical Spinal Cord Injury Treated by Surgery and Their Prognostic Factors

Outcomes of Patients with Cervical Spinal Cord Injury Treated by Surgery and Their Prognostic Factors

Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies

The Neuroprotective Mechanism of Spinal Cord Stimulation in Spinal Cord Ischemia/Reperfusion Injury

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