Autophagy Activation Contributes to the Neuroprotection of Remote Ischemic Perconditioning Against Focal Cerebral Ischemia in Rats

Su, Jingyuan; Zhang, Tingting; Wang, Kanwen; Zhu, Tingzhun; Li, Xiaoming

doi:10.1007/s11064-014-1396-x

Cited by 73 publications

(54 citation statements)

References 30 publications

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“…Several evidences suggest that some proteolytic enzymes, such as calcium-dependent cysteine proteases, are associated with the origin and development of OPIDN [8,14]. Autophagy is an evolutionarily conserved process that can lead to degradation of proteins and entire organelles in eukaryotic cells [15,16]. In response to nutrient-limiting conditions or environmental insults, the autophagy is initiated to form double-membrane autophagosomes.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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Organophosphate-induced delayed neuropathy (OPIDN) is pathologically characterized by the swollen axon containing aggregations of microtubules, neurofilaments, smooth endoplasmic reticulum and multivesicular vesicles. At present, the exact mechanism of OPIDN is unclear and the effective therapeutic methods is not available to counter this syndrome. Recent studies had shown that the autophagy was involved in OPIDN. The adipocytokine Apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous system. Recent researches illuminated that Apelin was neuroprotective factor and Apelin could regulate the autophagy in vivo and vitro model. So we investigated the effect of Apelin-13 on the OPIDN induced by Tri-ortho-cresyl phosphate (TOCP) in hens and explored the role of autophagy in Apelin-13 preventing OPIDN. Adult Roman hens were given a single dose of 750 mg/kg TOCP by gavage for 21 days to induce OPIDN, and neural dysfunction were detected, and the formation of autophagosomes in spinal cord neurons was observed by transmission electron microscopy, and the molecular markers of autophagy microtubule-associated protein light chain-3 (LC3) and the autophagy substrates p62/SQSTM1 were determined by Western blot analysis. The results demonstrated that the obvious neurological dysfunction such as hindlimb paralysis and paralysis of gait was present, the number of autophagosomes in the neurons of spinal cords was significantly increased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly increased in the OPIDN model group compared with the control group. Compared with the OPIDN model group, the neurological dysfunction of tens was obviously reduced, the clinical signs scores was significantly decreased, the number of autophagosomes in the neurons of hen spinal cords was significantly decreased, the level of LC3-II and p62 expressions and the ratio of LC3-II/LC3-I in spinal cords and sciatic nerve were significantly decreased in Apelin-13 treatment group. Our results suggested that Apelin-13 prevented against the OPIDN induced by TOCP in hens, which the mechanism might be associated with regulation autophagy flux by Apelin-13.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

et al. 2015

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“…Increased autophagy was involved in neuroprotection thus acting as a compensatory protective program for I/R injury [38, 39]. Suppressed autophagy was reported to be associated with neural loss and neurobehavioral deficits in mice, eventually leading to neurodegenerative diseases [40, 41].…”

Section: Discussionmentioning

confidence: 99%

Mitofusin 2 Exerts a Protective Role in Ischemia Reperfusion Injury Through Increasing Autophagy

Peng

Rao

Zhang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Autophagy is essential for maintaining cellular homeostasis and the survival of terminally differentiated cells as neurons. In this study, we aim to investigate whether mitofusin 2, a mitochondrial fusion protein, mediates autophagy in cerebral ischemia/reperfusion (I/R) injury. Methods: Primary cultured neurons were treated with oxygen-glucose deprivation/reperfusion to mimic cerebral I/R injury in vitro. Autophagosomes were visualized upon TEM. Autophagy-markers were then detected to monitor autophagy by western-blot and real-time PCR, and the autophagic flux was tracked with a mRFP-GFP-LC3 construct by fluorescence as well as autophagy inhibitors and agonists. The up- and downregulation of Mfn2 were through transfecting a lentivirusexpression vector respectively. And neuronal injury was detected by cell counting kit and TUNEL assay. Results: Results showed I/R increased autophagosome formation and inhibited autolysosome degradation. Furthermore, use of autophagy related agents demonstrated that I/R injury was caused by insufficient autophagy and aggravated by impaired autophagic degradation. The results also indicated that mitofusin 2 could ameliorate I/R injury through increasing autophagosome formation and promoting the fusion of autophagosomes and lysosomes. In contrast, downregulation of mitofusin 2 aggravated the I/R injury by inhibiting autophagosome formation and the fusion of autophagosomes and lysosomes. Additionly, mitofusin 2 overexpression did not lead to autolysosome accumulation induced by I/R. Conclusions: In summary, this study explicitly demonstrated that mitofusin 2 could ameliorate I/R injury mainly through promoting autophagy, which represented a potential novel strategy for neuroprotection against cerebral I/R damage.

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“…Study 4 examines the effects of two treatments and an inhibitor on infarction reduction [24]. Using the infarct volumes calculated by Lin et al’s algorithm, the infarct volume is statistically lower in the MCAO+Treatment 1, MCAO+Treatment 1+Vehicle, and MCAO+Treatment 2 groups compared to that of the MCAO, MCAO+Treatment 1+Inhibitor, and MCAO+Vehicle groups ( p <0.05 for MCAO vs. MCAO+Treatment 1, MCAO+Treatment 1+Vehicle, and MCAO+Treatment 2; p <0.05 for MCAO+Treatment 1+In-hibitor vs. MCAO+Treatment 1, MCAO+Treatment 1+Ve-hicle, and MCAO+Treatment 2; p <0.05 for MCAO+Vehicle vs. MCAO+Treatment 1, MCAO+Treatment 1+Vehicle, and MCAO+Treatment 2).…”

Section: Resultsmentioning

confidence: 99%

“…The search, performed on January 21, 2015, yielded 544 hits, of which 13 satisfied the inclusion criteria: adult Sprague-Dawley rats given food and water ad libitum, 2 h of MCAO using the intraluminal suture model, animals sacrificed 24 h post-ictus, TTC-stained brain slices, and infarct quantification using the indirect method of Lin et al [12]. Of the 13 publications, four were chosen and used to compare our algorithm with that of Lin et al [21–24]. …”

Section: Methodsmentioning

confidence: 99%

“…When Lin et al’s algorithm is used in the four published studies examined herein [21–24], statistical significance is achieved for the treatment groups when the infarct volumes are reduced by a minimum of 20 %. However, when our algorithm is used, for statistical significance to be observed between the treated and untreated groups, the infarctions must be reduced by a minimum of 32 %.…”

Section: Impact Of Our Algorithm On Clinical Trial Drug Candidatesmentioning

confidence: 99%

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Correcting for Brain Swelling’s Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats

McBride

Klebe

Tang

et al. 2015

Transl. Stroke Res.

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Evaluating infarct volume is the primary outcome for experimental ischemic stroke studies and is a major factor in determining translation of a drug into clinical trials. Numerous algorithms are available for evaluating this critical value, but a major limitation of current algorithms is that brain swelling is not appropriately considered. The model by Lin et al. is widely used, but overestimates swelling within the infarction, yielding infarct volumes which do not reflect the true infarct size. Herein, a new infarct volume algorithm is developed to minimize the effects of both peri-infarct and infarct core swelling on infarct volume measurement. 2,3,5-Triphenyl-2H-tetrazolium chloride-stained brain tissue of adult rats subjected to middle cerebral artery occlusion was used for infarct volume analysis. When both peri-infarct swelling and infarction core swelling are removed from infarct volume calculations, such as accomplished by our algorithm, larger infarct volumes are estimated than those of Lin et al.’s algorithm. Furthermore, the infarct volume difference between the two algorithms is the greatest for small infarcts (<10 % of brain volume) when peri-infarct swelling is the greatest. Finally, using data from four published studies, our algorithm is compared to Lin et al.’s algorithm. Our algorithm offers a more reliable estimation of the infarct volume after ischemic brain injury, and thus may provide the foundation for comparing infarct volumes between experimental studies and standardizing infarct volume quantification to aid in the selection of the best candidates for clinical trials.

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Autophagy Activation Contributes to the Neuroprotection of Remote Ischemic Perconditioning Against Focal Cerebral Ischemia in Rats

Cited by 73 publications

References 30 publications

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

RETRACTED ARTICLE: Apelin-13 Prevents the Delayed Neuropathy Induced by Tri-ortho-cresyl Phosphate Through Regulation the Autophagy Flux in Hens

Mitofusin 2 Exerts a Protective Role in Ischemia Reperfusion Injury Through Increasing Autophagy

Correcting for Brain Swelling’s Effects on Infarct Volume Calculation After Middle Cerebral Artery Occlusion in Rats

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