Plasma Erythropoietin, IL-17A, and IFNγ as Potential Biomarkers of Motor Function Recovery in a Canine Model of Spinal Cord Injury

Zhang, Lijian; Zhuang, Xiaoqing; Chen, Yao; Zhanfeng, Niu; Xia, Hechun

doi:10.1007/s12031-020-01575-y

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…Various animal models have been widely developed to investigate the pathological consequences of SCI and establish an effective treatment basis [ 10 , 11 ]. The canine SCI model has recently gained attention as a translational model for confirming and extending results from rodent investigations of SCI therapies [ 12 , 13 ]. In addition, unlike many rodents, severe SCI in dogs does not show a remarkable spontaneous recovery [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model

Metwally

Al-Abbadi

Hashem

et al. 2022

IJMS

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Calpain activation has been implicated in various pathologies, including neurodegeneration. Thus, calpain inhibition could effectively prevent spinal cord injury (SCI) associated with neurodegeneration. In the current study, a dog SCI model was used to evaluate the therapeutic potential of a selective calpain inhibitor (PD150606) in combination with methylprednisolone sodium succinate (MPSS) as an anti-inflammatory drug. SCI was experimentally induced in sixteen mongrel dogs through an epidural balloon compression technique. The dogs were allocated randomly into four groups: control, MPSS, PD150606, and MPSS+PD150606. Clinical evaluation, serum biochemical, somatosensory evoked potentials, histopathological, and immunoblotting analyses were performed to assess treated dogs during the study. The current findings revealed that the combined administration of MPSS+PD150606 demonstrated considerably lower neuronal loss and microglial cell infiltration than the other groups, with a significant improvement in the locomotor score. The increased levels of inflammatory markers (GFAP and CD11) and calcium-binding proteins (Iba1 and S100) were significantly reduced in the combination group and to a lesser extent in MPSS or PD150606 treatment alone. Interestingly, the combined treatment effectively inhibited the calcium-induced cleavage of p35, limited cdk5 activation, and inhibited tau phosphorylation. These results suggest that early MPSS+PD150606 therapy after acute SCI may prevent subsequent neurodegeneration via calpain inhibition.

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Section: Introductionmentioning

confidence: 99%

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model

Metwally

Al-Abbadi

Hashem

et al. 2022

IJMS

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“…29 These data reveal novel panels of inflammation-related cytokines, which have the potential to be evaluated as biomarkers for predicting motor function prognosis after SCI. 30 …”

Section: Discussionmentioning

confidence: 99%

“…29 These data reveal novel panels of inflammation-related cytokines, which have the potential to be evaluated as biomarkers for predicting motor function prognosis after SCI. 30 The included studies may be highly heterogeneous in the doses used and the methods of neurological function assessment. A systematic review will be constructed if heterogeneity does not allow a meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

Recombinant human erythropoietin plus methylprednisolone versus methylprednisolone in treatment of acute spinal cord injury：protocol for a systematic review and meta-analysis

et al. 2022

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IntroductionRecent studies in animal models indicate that recombinant human erythropoietin (rHuEPO) is very effective in enhancing neurological recovery after spinal cord injury (SCI). We described a protocol aimed at evaluating the efficacy of rHuEPO plus methylprednisolone (MP) compared with MP alone in improving neurological function of patients with SCI in randomised controlled trials (RCTs).Methods and analysisThis study aims to explore the effect of rHuEPO combined with MP on neurological function in patients with SCI through a meta-analysis. To this end, the authors will search eight research databases for data retrieval: MEDLINE, China National Knowledge Infrastructure, Wan Fang, China Biology Medicine dis, Web of Science, PubMed, Cochrane and Embase for RCTs on SCI in any language. The primary outcome will be the American Spinal Injury Association score at the time of follow-up. The secondary outcomes will be the WHOQOL-100 instrument score, neurophysiological state and related factors. Two authors will independently search literature records, scan titles, abstracts and full texts, collect data, and assess materials for risk of bias. Stata V.14.0 will be used for statistical analysis.Ethics and disseminationThis research is exempt from ethics approval because the work is carried out on published documents. We will disseminate this protocol in scientific conferences and a peer-reviewed journal.PROSPERO registration numberCRD42021260688.

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“…Erythropoietin is highly expressed in central nervous system cells, exerting neurotrophic, neuronal anti-apoptotic, antioxidant, and anti-inflammatory effects through an autocrine and paracrine approach. There are currently few studies on the therapeutic effects of the combination of erythropoietin and methylprednisolone in the treatment of ischemic and reperfusion spinal cord injuries in patients with CM [ 11 , 12 ]. Against this background, this study analyzed the therapeutic effects of combined erythropoietin and methylprednisolone therapy on the treatment of ischemia-reperfusion injuries of the spinal cord in patients with cervical spine myelopathy and its impact on the levels of interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1RA), and interleukin-8 (IL-8), which are considered to be the indicators of ischemia-reperfusion injury to the spinal cord in patients with cervical spondylotic myelopathy.…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy

Eryilmaz¹,

Farooque²

2021

Cureus

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Introduction Cervical myelopathy (CM) is caused by degenerative or congenital changes in the discs and soft tissues of the cervical spine, leading to chronic compression of the spinal cord. The current treatment for moderate-tosevere CM is surgical decompression, which is effective in most cases; however, it can cause inflammation of the nervous system and spinal cord reperfusion injury, resulting in perioperative neurological complications and suboptimal neurological recovery. The aim of this study was to investigate the therapeutic effects of the combination of erythropoietin and methylprednisolone in the treatment of ischemia-reperfusion injury to the spinal cord and to analyze its effects on the levels of interleukin-1 beta (IL-1β), interleukin-1 receptor antagonist (IL-1RA), and interleukin-8 (IL-8). Materials and methods This study included 110 patients admitted to the hospital due to cervical spondylotic myelopathy. They were randomized into two groups of 55 patients each: a control and an observation group. In both groups of patients, fusion internal fixation and anterior cervical discectomy were performed. The difference, however, was that the control group received a rapid intravenous injection of 30 mg/kg methylprednisolone 30 minutes prior to spinal cord decompression, while the observation group received an intravenous injection of 30 mg/kg methylprednisolone and 3,000 U/kg erythropoietin 30 minutes before spinal cord decompression. The study was approved by the Hospital Ethical Committee of the Dow University of Health Sciences, Karachi. The neurological function of both groups of patients was assessed before the procedure and three months after the treatment using the Japanese Orthopedic Association (JOA) method of assessing spinal cord function (40-point rating method). Enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of neuron-specific enolase (NSE), S-100β, IL-1RA, IL-1β, and IL-8 in both groups. The quality of life of patients in both groups was assessed three months after the treatment with the World Health Organization Quality of Life assessment instrument (WHOQOL-100). Results Before the treatment, there was no significant variance between the two groups in the JOA score and the 40point rating method. Similarly, there was no significant difference in the levels of IL-1β, IL-1RA, and IL-8 between the two groups (p-value = 0.262, 0.387, and 0.154 respectively) prior to the treatment. Three months after the treatment, the levels of IL-1β and IL-8 in the observation group were 21.83 ±3.65 ng/l and 357.07 ±32.36 ng/l respectively, both lower than the control group value (p-value = 0.026, 0.028 respectively). The level of IL-1RA in follow-up was 21.59 ±1.15 ng/l, which was higher than that in the control group. Three months after the treatment, all the WHOQOL-100 parameters of the observation group for psychology, physiology, social relations, independence, spirituality, environment, and general quality of life were higher than those of the control group; the variance ...

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Plasma Erythropoietin, IL-17A, and IFNγ as Potential Biomarkers of Motor Function Recovery in a Canine Model of Spinal Cord Injury

Cited by 6 publications

References 46 publications

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model

Selective Calpain Inhibition Improves Functional and Histopathological Outcomes in a Canine Spinal Cord Injury Model

Recombinant human erythropoietin plus methylprednisolone versus methylprednisolone in treatment of acute spinal cord injury：protocol for a systematic review and meta-analysis

The Efficacy of Combined Medication With Methylprednisolone and Erythropoietin in the Treatment of Ischemia-Reperfusion Injury to the Spinal Cord in Patients With Cervical Spondylotic Myelopathy

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