CaSR and calpain contribute to the ischemia reperfusion injury of spinal cord

Sun, Jie; Yang, Huilin; Huang, Yonghui; Chen, Qian; Cao, Xiaojian; Li, Dapeng; Haoming, Shu; Jiang, Run-Yu

doi:10.1016/j.neulet.2017.03.009

Cited by 9 publications

(3 citation statements)

References 27 publications

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Section: Discussionmentioning

confidence: 99%

“…At present, domestic and foreign studies have shown that one of the mechanisms of pathogenesis in SCIRI is the disturbance of calcium balance, including extracellular calcium influx, increase of calcium release from the ER and eventual intracellular calcium overload. 39,40 Intracellular calcium homeostasis is primarily maintained by the ER and plays an important role in spinal cord injury after ischaemia/reperfusion. 4 Mild tissue ischaemia/reperfusion can lead to ER dysfunction and induces the unfolded protein response of the ER, thereby relieving cellular stress and protecting cells from apoptosis or necrosis.…”

Section: Spinal Cord Ischaemia-reperfusion Injury Can Lead To Dysfuncmentioning

confidence: 99%

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Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia‐reperfusion injury by targeting the CNPY2‐endoplasmic reticulum stress signalling

Zhao

Zhai

et al. 2019

J Cellular Molecular Medi

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Dexmedetomidine (Dex) has been proven to exert protective effects on multiple organs in response to ischaemia‐reperfusion injury, but the specific mechanism by which this occurs has not been fully elucidated. The purpose of this study was to investigate whether Dex attenuates spinal cord ischaemia‐reperfusion injury (SCIRI) by inhibiting endoplasmic reticulum stress (ERS). Our team established a model of SCIRI and utilized the endoplasmic reticulum agonist thapsigargin. Dex (25 g/kg) was intraperitoneally injected 30 minutes before spinal cord ischaemia. After 45 minutes of ischaemia, the spinal cord was reperfused for 24 hours. To evaluate the neuroprotective effect of Dex on SCIRI, neurological function scores were assessed in rats and apoptosis of spinal cord cells was determined by TUNEL staining. To determine whether the endoplasmic reticulum apoptosis pathway CNPY2‐PERK was involved in the neuroprotective mechanism of Dex, the expression levels of related proteins (CNPY2, GRP78, PERK, CHOP, caspase‐12, caspase‐9 and caspase‐3) were detected by western blot analysis and RT‐PCR. We observed that Dex significantly increased the neurological function scores after SCIRI and decreased apoptosis of spinal cord cells. The expression of ERS‐related apoptosis proteins was significantly increased by SCIRI but was significantly decreased in response to Dex administration. Taken together, the results of this study indicate that Dex may attenuate SCIRI by inhibiting the CNPY2‐ERS apoptotic pathway.

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Section: Discussionmentioning

confidence: 99%

Section: Spinal Cord Ischaemia-reperfusion Injury Can Lead To Dysfuncmentioning

confidence: 99%

Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia‐reperfusion injury by targeting the CNPY2‐endoplasmic reticulum stress signalling

Zhao

Zhai

et al. 2019

J Cellular Molecular Medi

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“…The influx of Ca +2 stimulates Ca +2 -dependent enzymes, within them are calpains, which seem to play a role in proteolysis by contributing to apoptosis in CNS cells. The cell death decreases mRNA expression and transcription of myelin basic protein (MBP) and proteolipid protein (PLP), which are axonal neurofilament proteins [49,51,52]. The administration of a calpain inhibitor such as E-64-d (1 mg/kg) to injured rats blocks apoptosis and helps to re-establish MBP and PLP genes [51].…”

Section: Treatment Outcomementioning

confidence: 99%

Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art

Rodríguez-Barrera¹,

Garibay-López²,

Ibarra³

2020

Neuroprotection - New Approaches and Prospects

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Spinal cord injury (SCI) is an important pathology leading to possibly fatal consequences. The most common repercussions are those affecting motor and sensitivity skills. SCI-damage occurs in its first phase-as a result of the lesion mechanism (contusion, compression, transection, and primary lesion). After this primary damage, there is a second phase with further deleterious effects on neural degeneration and tissue restoration. At the moment, several investigation groups are working on developing therapeutic strategies to induce neuroprotection. This chapter pretends to introduce the reader to a wide range of these therapies, particularly those with promising results and tested in preclinical and clinical studies. In the first section, physiopathology of SCI will be addressed. Afterwards, the chapter will review neuroprotective strategies such as cyclooxygenase, calpain, and apoptosis inhibitors. Finally, the effect of immunophilin ligands, neural-derived peptides, antioxidants, hypoglycemic agent, gonadal hormones, Na channel blockers, and transplant of cultured cells will also be reviewed.

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Upregulation of miR-199a-5p Protects Spinal Cord Against Ischemia/Reperfusion-Induced Injury via Downregulation of ECE1 in Rat

Bao

Fang

et al. 2018

Cell Mol Neurobiol

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Ischemia-reperfusion (I/R)-induced spinal cord injury can cause apoptotic damage and subsequently act as a blood-spinal cord barrier damage. MicroRNAs (miRNAs) contributed to the process of I/R injury by regulating their target mRNAs. miR-199a-5p is involved in brain and heart I/R injury; however, its function in the spinal cord is not yet completely clarified. In this study, we investigated the role of miR-199a-5p on spinal cord I/R via the endothelin-converting enzyme 1, especially the apoptosis pathway. In the current study, the rat spinal cord I/R injury model was established, and the Basso Beattie Bresnahan scoring, Evans blue staining, HE staining, and TUNEL assay were used to assess the I/R-induced spinal cord injury. The differentially expressed miRNAs were screened using microarray. miR-199a-5p was selected by unsupervised hierarchical clustering analysis. The dual-luciferase reporter assay was used for detecting the regulatory effects of miR-199a-5p on ECE1. In addition, neuron expression was detected by immunostaining assay, while the expressions of p-ERK, ERK, p-JNK, JNK, caspase-9, Bcl-2, and ECE1 were evaluated by Western blot. The results indicated the successful establishment of the I/R-induced spinal cord injury model; the I/R induced the damage to the lower limb motor. Furthermore, 18 differentially expressed miRNAs were detected in the I/R group compared to the sham group, and miR-199a-5p protected the rat spinal cord injury after I/R. Moreover, miR-199a-5p negatively regulated ECE1, and silencing the ECE1 gene also protected the rat spinal cord injury after I/R. miR-199a-5p or silencing of ECE1 also regulated the expressions of caspase-9, Bcl-2, p-JNK, p-ERK, and ECE1 in rat spinal cord injury after I/R. Therefore, we demonstrated that miR-199a-5p might protect the spinal cord against I/R-induced injury by negatively regulating the ECE1, which could aid in developing new therapeutic strategies for I/R-induced spinal cord injury.

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CaSR and calpain contribute to the ischemia reperfusion injury of spinal cord

Cited by 9 publications

References 27 publications

Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia‐reperfusion injury by targeting the CNPY2‐endoplasmic reticulum stress signalling

Dexmedetomidine attenuates neuronal injury after spinal cord ischaemia‐reperfusion injury by targeting the CNPY2‐endoplasmic reticulum stress signalling

Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art

Upregulation of miR-199a-5p Protects Spinal Cord Against Ischemia/Reperfusion-Induced Injury via Downregulation of ECE1 in Rat

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