Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Dixon, Brandon; Chen, Di; Zhang, Yang; Flores, Jerry; Malaguit, Jay; Nowrangi, Derek; Zhang, Junyi; Tang, Jiping

doi:10.1177/1759091416670492

Cited by 27 publications

(11 citation statements)

References 72 publications

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“…Besides, evidences also showed that ERK1/2 and JAK/STAT3 pathways participated in pro-angiogenesis after stroke [39,40]. JAK1/ STAT3 pathway was reported to participate in neuronal apoptosis in a rat model of neuronal hypoxic-ischemic encephalopathy [41]. Our results went in line with these earlier investigations.…”

Section: Discussionsupporting

confidence: 91%

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

et al. 2020

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Nowadays, searching for new therapeutic targets for cerebral stroke treatment are still in urgent need. Our study explored the influences and mechanisms of HIF-1α on OGD/R-evoked injury. OGD/R treatment was conducted on PC12 cells to simulate ischemic injury. CCK-8, flow cytometry and qRT-PCR were conducted to determine the variations of cell viability, apoptosis and gene expression, respectively. Cell transfections were conducted to overexpress HIF-1α and miR-134. Variations of protein levels were evaluated by employing western blot. Results showed that OGD/R treatment induced cell injury through reducing viability, while enhancing apoptosis that was validated by the elevated ratios of C/P-PARP and C/ P-caspase-3. HIF-1α expression was markedly increased by OGD/R treatment. HIF-1α overexpression attenuated OGD/R-evoked injury in PC12 cells and remarkably reversed OGD/R-triggered inhibitory effects on ERK1/2 and JAK1/STAT3 pathways. Besides, miR-134 was also down-regulated by HIF-1α overexpression in PC12 cells. Up-regulation of miR-134 notably counteracted HIF-1α overexpression-triggered neuroprotective impacts on OGD/R-evoked injury and ERK1/2 and JAK1/STAT3 pathways. Our present study reported that HIF-1α overexpression protected PC12 cells against OGD/R-evoked injury via downregulation of miR-134, which making HIF-1α and miR-134 to be promising targets for cerebral stroke therapy.

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Section: Discussionsupporting

confidence: 91%

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

et al. 2020

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“…The sections were imaged by microscope (Olympus-BX51). Brain tissue loss and ventricular dilation were measured and calculated with ImageJ 4.0 (Media Cybernetics) (Ballabh, 2010; Dixon et al, 2016). Calculations were performed in a blinded fashion.…”

Section: Methodsmentioning

confidence: 99%

Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2/AMPK/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats

Zhang

Ding

et al. 2018

Brain, Behavior, and Immunity

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Chemerin, an adipokine, has been reported to reduce the production of pro-inflammatory cytokines and neutrophil infiltration. This study investigated the role of Chemerin and its natural receptor, ChemR23, as well as its downstream mediator calmodulin-dependent protein kinase kinase 2 (CAMKK2)/adenosine monophosphate-activated protein kinase (AMPK) /Nuclear factor erythroid 2-related factor 2 (Nrf2) following germinal matrix hemorrhage (GMH) in neonatal rats, with a specific focus on inflammation. GMH was induced by intraparenchymal injection of bacterial collagenase (0.3U) in P7 rat pups. The results demonstrated that human recombinant Chemerin (rh-Chemerin) improved neurological and morphological outcomes after GMH. Rh-Chemerin promoted accumulation and proliferation of M2 microglia in periventricular regions at 72 h. Rh-Chemerin increased phosphorylation of CAMKK2, AMPK and expression of Nrf2, and decreased IL-1beta, IL-6 and TNF-alpha levels. Selective inhibition of ChemR23/CAMKK2/AMPK signaling in microglia via intracerebroventricular delivery of liposome-encapsulated specific ChemR23 (Lipo-alpha-NETA), CAMKK2 (Lipo-STO-609) and AMPK (Lipo-Dorsomorphin) inhibitor increased the expression levels of IL-1beta, IL-6 and TNF- alpha, demonstrating that ChemR23/CAMKK2/AMPK signaling in microglia suppressed inflammatory response after GMH. Cumulatively, these data showed that rh-Chemerin ameliorated GMH-induced inflammatory response by promoting ChemR23/CAMKK2/AMPK/Nrf2 pathway, and M2 microglia may be a major mediator of this effect. Thus, rh-Chemerin can serve as a potential agent to reduce the inflammatory response following GMH.

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“…Fluoro-Jade C staining was used to detect degenerating neurons in the brain (Dixon et al, 2016). Briefly, brain sections were rinsed in basic alcohol consisting of 1% sodium hydroxide in 80% ethanol, 70% ethanol, distilled water, 0.06% potassium permanganate, 0.0001% solution of Fluoro-Jade C (Histo-chem) dissolved in 0.1% acetic acid vehicle, distilled water and xylene.…”

Section: Methodsmentioning

confidence: 99%

Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats

Zhang

Tucker

DongYan

et al. 2018

Neurochemistry International

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Hypoxic-ischemic (HI) encephalopathy is a leading cause of dire mortality and morbidity in neonates. Unfortunately, no effective therapies have been developed as of yet. Oxidative stress plays a critical role in pathogenesis and progression of neonatal HI. Previously, as a Nrf2 activator, tert-butylhydroquinone (TBHQ) has been demonstrated to exert neuroprotection on brain trauma and ischemic stroke models, as well as oxidative stress-induced cytotoxicity in neurons. It is, however, still unknown whether TBHQ administration can protect against oxidative stress in neonatal HI brain injury. This study was undertaken to determine the neuroprotective effects and mechanisms of TBHQ post-treatment on neonatal HI brain damage. Using a neonatal HI rat model, we demonstrated that TBHQ markedly abated oxidative stress compared to the HI group, as evidenced by decreased oxidative stress indexes, enhanced Nrf2 nuclear accumulation and DNA binding activity, and up-regulated expression of Nrf2 downstream antioxidative genes. Administration of TBHQ likewise significantly suppressed reactive gliosis and release of inflammatory cytokines, and inhibited apoptosis and neuronal degeneration in the neonatal rat cerebral cortex. In addition, infarct size and neuronal damage were attenuated distinctly. These beneficial effects were accompanied by improved neurological reflex and motor coordination as well as amelioration of spatial learning and memory deficits. Overall, our results provide the first documentation of the beneficial effects of TBHQ in neonatal HI model, in part conferred by activation of Nrf2 mediated antioxidative signaling pathways.

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Intranasal Administration of Interferon Beta Attenuates Neuronal Apoptosis via the JAK1/STAT3/BCL-2 Pathway in a Rat Model of Neonatal Hypoxic-Ischemic Encephalopathy

Cited by 27 publications

References 72 publications

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

RETRACTED ARTICLE: Overexpression of HIF-1α protects PC12 cells against OGD/R-evoked injury by reducing miR-134 expression

Chemerin suppresses neuroinflammation and improves neurological recovery via CaMKK2/AMPK/Nrf2 pathway after germinal matrix hemorrhage in neonatal rats

Tert-butylhydroquinone post-treatment attenuates neonatal hypoxic-ischemic brain damage in rats

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