The Neuroprotective Effect of Coumaric Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats

Güven, Mustafa; Şehitoğlu, Müşerref Hilal; Yüksel, Yasemin Topal; Tokmak, Mehmet; Aras, Adem Bozkurt; Akman, Tolga; Gölge, Umut Hatay; Karavelioğlu, Ergün; Bal, Ercan; Çoşar, Murat

doi:10.1007/s10753-015-0179-0

Cited by 20 publications

(9 citation statements)

References 28 publications

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“…Secondly, the function of neuro-inflammation was only tested in the ischemic stroke model. However, inflammation participates in different types of injuries, including central [39–41] and peripheral nervous system [42]. Further studies are required to fully depict the role of inflammation in other neurological pathologies.…”

Section: Discussionmentioning

confidence: 99%

Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation

Zhao

Jiang

et al. 2019

J Neuroinflammation

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Background Functions of astrocytes in the rehabilitation after ischemic stroke, especially their impacts on inflammatory processes, remain controversial. This study uncovered two phenotypes of astrocytes, of which one was helpful, and the other harmful to anoxic neurons after brain ischemia. Methods We tested the levels of inflammatory factors including TNF-a, IL-6, IL-10, iNOS, IL-1beta, and CXCL10 in primary astrocytes at 0 h, 6 h, 12 h, 24 h, and 48 h after OGD, grouped the hypoxia astrocytes into iNOS-positive (iNOS(+)) and iNOS-negative (iNOS(−)) by magnetic bead sorting, and then co-cultured the two groups of cells with OGD-treated neurons for 24 h. We further verified the polarization of astrocytes in vivo by detecting the co-localization of iNOS, GFAP, and Iba-1 on MCAO brain sections. Lentivirus overexpressing LCN2 and LCN2 knockout mice (#024630. JAX, USA) were used to explore the role of LCN2 in the functional polarization of astrocytes. 7.0-T MRI scanning and the modified Neurological Severity Score (mNSS) were used to evaluate the neurological outcomes of the mice. Results After oxygen-glucose deprivation (OGD), iNOS mRNA expression increased to the peak at 6 h in primary astrocytes, but keep baseline expression in LCN2-knockout astrocytes. In mice with transient middle cerebral artery occlusion (tMCAO), LCN2 was proved necessary for astrocyte classical activation. In LCN2 knockout mice with MCAO, no classically activated astrocytes were detected, and smaller infarct volumes and better neurological functions were observed. Conclusions The results indicated a novel pattern of astrocyte activation after ischemic stroke and lipocalin-2 (LCN2) plays a key role in polarizing and activating astrocytes.

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Section: Discussionmentioning

confidence: 99%

Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation

Zhao

Jiang

et al. 2019

J Neuroinflammation

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“…1, 3, 5, and 7 days postoperatively, eight rats from each group were randomly selected for evaluation of hindlimb motor function by using the inclined plane test [ 31 ] and modified Tarlov scoring system [ 32 ].…”

Section: Methodsmentioning

confidence: 99%

Synthesis of methylprednisolone loaded ibuprofen modified dextran based nanoparticles and their application for drug delivery in acute spinal cord injury

Jiang

Cui

et al. 2017

Oncotarget

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To improve the therapeutic efficacy of spinal cord injury (SCI), the methylprednisolone was incorporated into nanoparticles based on the ibuprofen modified dextran. The ibuprofen modified dextran was synthesized using a direct esterification linkage between the carboxylic acids of hydrophobic drug and the hydroxyl groups of the polymer backbone. The morphology of methylprednisolone loaded nanoparticles was evaluated by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The therapeutic efficacy of the prepared nanoparticles on the acute SCI model rats was assessed. It is demonstrated that methylprednisolone loaded ibuprofen modified dextran based nanoparticles (MP-loaded NPs) could promote the recovery of neurological deficits, enhance growth of neurons, decrease degeneration of injuried neurons and reduce the tissue tumor necrosis factor alpha (TNF-α) levels significantly in the SCI rats. Subsequently, the study indicates that synthesis of methylprednisolone loaded ibuprofen modified dextran based nanoparticles has a great potential in the synergetic effect treatment for spinal cord injury and nanoparticles based drug delivery system will become a powerful weapon of human conquest of disease.

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“…In final remarks, addressing the rationale of the applied methodology, it has to be noted that the applied dose of PTX was within the range of those used in other experiments on rats: 100 mg/kg body weight vs. 30–300 mg/kg body weight [ 21 , 25 , 27 ], and its application at this dose prior to IRI was previously found by us to be nephroprotective, as opposed to intra- or post-IRI administration [ 10 ]. On the other hand, the dosage of MP (100 mg/kg body weight) was higher than that usually studied in IRI rat models (30 mg/kg body weight) [ 32 , 33 ]. This more intense steroid treatment was based on our previous experiments with MP doses ranging from 15 to 100 mg/kg body weight, which showed the long-term kidney protection from IRI only with the highest dosage [ 34 ].…”

Section: Discussionmentioning

confidence: 97%

Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion

Wystrychowski

Grzeszczak

et al. 2018

IJMS

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Renal ischemia-reperfusion injury (IRI) induces local inflammation leading to kidney damage. Since pentoxifylline (PTX) and steroids have distinct immunomodulatory properties, we aimed to evaluate for the first time their combined use in IRI-induced acute kidney injury (AKI) and chronic kidney disease (CKD) in rats. In two experiments, PTX (100 mg/kg body weight subcutaneously) was administered 90 min prior to renal IRI or/and methylprednisolone (MP; 100 mg/kg body weight intramuscularly) was infused 60 min after reperfusion of a solitary kidney (AKI model: 45 min ischemia, 48 male Sprague-Dawley rats) or one kidney with excision of contralateral kidney 2 weeks later (CKD model: 90 min ischemia, 38 rats). Saline was infused in place of PTX or/and MP depending on the group. Renal function (diuresis, serum creatinine, creatinine clearance, sodium and potassium excretion, and urine protein/creatinine) was assessed at 48 h and 120 h post-IRI (AKI model) or 4, 16 and 24 weeks after IRI, along with survival analysis (CKD model). More evidently at early stages of AKI or CKD, treated animals showed higher glomerular filtration and diminished tubular loss of electrolytes, more so with PTX + MP than PTX or MP (serum creatinine (μmol/L) at 48 h of AKI: 60.9 ± 19.1 vs. 131.1 ± 94.4 vs. 233.4 ± 137.0, respectively, vs. 451.5 ± 114.4 in controls, all p < 0.05; and at 4 weeks of CKD: 89.0 ± 31.9 vs. 118.1 ± 64.5 vs. 156.9 ± 72.6, respectively, vs. 222.9 ± 91.4 in controls, p < 0.05 for PTX or PTX + MP vs. controls and PTX + MP vs. MP). Survival was better by >2-fold with PTX + MP (89%) vs. controls (40%; p < 0.05). PTX + MP largely protect from IRI-induced AKI and CKD and subsequent mortality in rats. This calls for clinical investigations, especially in kidney transplantation.

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The Neuroprotective Effect of Coumaric Acid on Spinal Cord Ischemia/Reperfusion Injury in Rats

Cited by 20 publications

References 28 publications

Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation

Lipocalin-2 may produce damaging effect after cerebral ischemia by inducing astrocytes classical activation

Synthesis of methylprednisolone loaded ibuprofen modified dextran based nanoparticles and their application for drug delivery in acute spinal cord injury

Pentoxifylline and Methylprednisolone Additively Alleviate Kidney Failure and Prolong Survival of Rats after Renal Warm Ischemia-Reperfusion

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