Protective effects of melatonin on the white matter damage of neonatal rats by regulating NLRP3 inflammasome activity

Objective. Since oligodendrocyte progenitor cells (OPCs) are the target cells of neonatal hypoxic-ischemic encephalopathy (HIE), the present study was aimed at investigating the protective effects ofN-acetyl-L-cysteine (NAC), a well-known antioxidant and precursor of glutathione, in OPCs as well as in neonatal rats.Methods. Inin vitrostudy, protective effects of NAC on KCN cytotoxicity in F3.Olig2 OPCs were investigated via MTT assay and apoptotic signal analysis. Inin vivostudy, NAC was administered to rats with HIE induced by hypoxia-ischemia surgery at postnatal day 7, and their motor functions and white matter demyelination were analyzed.Results. NAC decreased KCN cytotoxicity in F3.Olig2 cells and especially suppressed apoptosis by regulating Bcl2 and p-ERK. Administration of NAC recovered motor functions such as the using ratio of forelimb contralateral to the injured brain, locomotor activity, and rotarod performance of neonatal HIE animals. It was also confirmed that NAC attenuated demyelination in the corpus callosum, a white matter region vulnerable to HIE.Conclusion. The results indicate that NAC exerts neuroprotective effectsin vitroandin vivoby preserving OPCs, via regulation of antiapoptotic signaling, and that F3.Olig2 human OPCs could be a good tool for screening of candidates for demyelinating diseases.

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The Neuroprotective Effects of Xenon on Neonatal Rats with White Matter Damage by Regulating Expression of microRNA-210 and HIF-1αThe Neuroprotective Effects of Xenon on Neonatal Rats with White Matter Damage by Regulating Expression of microRNA-210 and HIF-1α

10.21203/rs.3.rs-60259/v1 ◽

2020 ◽

Author(s):

Xiangyun Yin ◽

Jixiu Zhao ◽

Jian Jiang ◽

Hongmin Xi ◽

Xianghong Li ◽

...

Keyword(s):

White Matter ◽

Expression Level ◽

Neonatal Rats ◽

Rt Pcr ◽

White Matter Damage ◽

Neuroprotective Effects ◽

Brain White Matter ◽

Group A ◽

Group B ◽

Brain Tissues

Abstract Background:Premature infant is a significant health care burden. White matter damage (WMD) is a leading cause of acute mortality and chronic morbidity in preterm. Xenon (Xe) intervention was given to the 3-day-old neonatal rats with brain white matter injury. By detecting the changes in the expression level of microRNA210 and hypoxia inducible factor 1α (HIF-1α) in brain tissue before and after xenon intervention, we can research the molecular basis and the mechanism of neuroprotective on effect of xenon on brain white matter damage in neonatal rats.Methods:Three-day-old SD rats were randomly divided into sham group(Group A, n=24), lipopolysaccharide(LPS)+hypoxia-ischemia(HI) group (Group B, n=24) and LPS+HI+Xe group ( n=72). The onset of Xe inhalation started at 0,2 and 5 hours in subgroups C,D,and E respectively.We investigated the neurobehavioral deficits by performing TUNEL and hematoxylin and eosin (HE) staining and examining the expression of miR-210and HIF-1α in brain tissues via RT-PCR and western blot. Results: Xe treatment improved the histological alterations and decreased the number of apoptotic cells in group C pups.Compared to group A,Detection of miR-210 level by RT-PCR. the expression level of miR-210 in neonatal rats' periventricular tissue increased significantly at all time points in group B (p<0.05).While the expression level of miR-210 in brain tissues of group B was significantly lower at 48h and 72h than that of group C(p<0.05).Similarly,Detection of HIF-1α protein by Western blot. The level of HIF-1α protein in group B brain tissues was significantly higher than that of group A at each time point (p<0.05), Xe treatment resulted in a marked increase in HIF-1α in C,D, and E subgroups (P < 0.05, compared to group B).Conclusions: These results demonstrate that the expression of HIF-1α and miR-210 increased in periventricular tissues and Xe could relieve the white matter damage by up-regulating the expression of HIF-1α and its target gene miR-210.The Xe therapeutic time window was within 5 hours after intervention, the sooner the better.

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8 Impact of Inhaled Nitric Oxide on Hyperoxia-Induced White Matter Damage in Neonatal Rats

Archives of Disease in Childhood ◽

10.1136/archdischild-2012-302724.0008 ◽

2012 ◽

Vol 97 (Suppl 2) ◽

pp. A2-A3

Author(s):

H. Pham ◽

G. Vottier ◽

J. Pansiot ◽

B. Bollen ◽

H. Kadar ◽

...

Keyword(s):

Nitric Oxide ◽

White Matter ◽

Inhaled Nitric Oxide ◽

Neonatal Rats ◽

White Matter Damage

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Gestational Hypoxia Induces White Matter Damage in Neonatal Rats: A New Model of Periventricular Leukomalacia

Brain Pathology ◽

10.1111/j.1750-3639.2004.tb00492.x ◽

2004 ◽

Vol 14 (1) ◽

pp. 1-10 ◽

Cited By ~ 85

Author(s):

Olivier Baud ◽

Jean-Luc Daire ◽

Yvette Dalmaz ◽

Romain H Fontaine ◽

Richard C. Krueger ◽

...

Keyword(s):

White Matter ◽

Periventricular Leukomalacia ◽

Neonatal Rats ◽

White Matter Damage ◽

New Model

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4,4'-Diisothiocyanostilbene-2,2'-disulfonic Acid (DIDS) Ameliorates Ischemia-Hypoxia-Induced White Matter Damage in Neonatal Rats through Inhibition of the Voltage-Gated Chloride Channel ClC-2

International Journal of Molecular Sciences ◽

10.3390/ijms160510457 ◽

2015 ◽

Vol 16 (12) ◽

pp. 10457-10469 ◽

Cited By ~ 7

Author(s):

Baixiong Zhao ◽

Hongyu Quan ◽

Teng Ma ◽

Yanping Tian ◽

Qiyan Cai ◽

...

Keyword(s):

White Matter ◽

Chloride Channel ◽

Disulfonic Acid ◽

Neonatal Rats ◽

White Matter Damage ◽

Voltage Gated

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18β-Glycyrrhetinic Acid Protectes Neonatal Rats with Hyperoxia Exposure Through Inhibiting ROS/NF-κB/NLRP3 Inflammasome

10.21203/rs.3.rs-936715/v1 ◽

2021 ◽

Author(s):

Qing Cai ◽

Ziyun Liu ◽

Xuefei Yu ◽

Xinyi Zhao ◽

Xindong Xue ◽

...

Keyword(s):

Nlrp3 Inflammasome ◽

Inflammatory Responses ◽

Pulmonary Inflammation ◽

The Body ◽

Glycyrrhetinic Acid ◽

Pulmonary Insufficiency ◽

Protective Effects ◽

Neonatal Rats ◽

Alveolar Development ◽

Hyperoxia Exposure

Abstract Bronchopulmonary dysplasia (BPD) is a common devastating pulmonary complication in preterm infants. Oxygen supplementation is a lifesaving therapeutic measure used for premature infants with pulmonary insufficiency. However, oxygen toxicity is a significant trigger for BPD, and oxidative stress-induced inflammatory responses, in turn, worsens the oxidative toxicity resulting in lung injury and arresting of lung development. Glycyrrhiza radix is commonly used in the medicine and food industries. 18β-Glycyrrhetinic acid (18β-GA), a primary active ingredient of Glycyrrhiza radix, has a powerful anti-oxidative and anti-inflammatory effects. This study aimed to determine whether 18β-GA has protective effects on neonatal rats with hyperoxia exposure. Newborn Sprague-Dawley rats were kept in either 21% (normoxia) or 80% O2 (hyperoxia) continuously from postnatal day (PN) 1 to 14. 18β-GA was injected intragastrically at 50 or 100 mg/kg body weight once a day from PN 1 to 14. We examined the body weights and alveolar development, and measured ROS level and the markers of pulmonary inflammation. Mature-IL-1β and NF-κB pathway proteins, and the NLRP3 inflammasome, were assessed; concurrently, caspase-1 activity was measured. Our results indicated that hyperoxia resulted in alveolar simplification and decreased bodyweight of neonatal rats. Hyperoxia exposure increased ROS level and pulmonary inflammation, and activated NF-κB and the NLRP3 inflammasome. 18β-GA treatment decreased ROS level, inhibited the activation of NF-κB and the NLRP3 inflammasome, decreased pulmonary inflammation, improved alveolar development, and increased the bodyweight of neonatal rats with hyperoxia exposure. Our study demonstrates that 18β-GA protects neonatal rats with hyperoxia exposure through inhibiting ROS/NF-κB/NLRP3 inflammasome.

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Resveratrol improves cardiac function and left ventricular fibrosis after myocardial infarction in rats by inhibiting NLRP3 inflammasome activity and the TGF-β1/SMAD2 signaling pathway

PeerJ ◽

10.7717/peerj.11501 ◽

2021 ◽

Vol 9 ◽

pp. e11501

Author(s):

Jinjin Jiang ◽

Xiuping Gu ◽

Huifeng Wang ◽

Shibin Ding

Keyword(s):

Myocardial Infarction ◽

Cardiac Function ◽

Signaling Pathway ◽

Rat Model ◽

Nlrp3 Inflammasome ◽

Interstitial Fibrosis ◽

Left Ventricular ◽

Sham Operation ◽

Protective Effects ◽

Inflammasome Activity

Background Several studies have shown that resveratrol (RES), a naturally occurring polyphenol found in many plants, is beneficial for preventing cardiovascular diseases. However, the mechanism underlying the RES-mediated protection against myocardial infarction has not yet been revealed entirely. In this study, we investigated the protective effects of RES on cardiac function in a rat model of acute myocardial infarction (AMI) and the related underlying mechanisms. Methods Male Sprague-Dawley rats were randomly divided into four groups: Sham (sham operation), Sham-RES, AMI (AMI induction), and AMI-RES. The rat AMI model was established by the permanent ligation of left anterior descending coronary artery method. The rats in the RES-treated groups were gavaged with RES (50 mg/kg/day) daily for 45 days after the Sham operation or AMI induction; rats in the Sham and AMI groups were gavaged with deionized water. Cardiac function was evaluated by echocardiography. Atrial interstitial fibrosis was assessed by hematoxylin-eosin or Masson’s trichrome staining. Real-time PCR and western blotting analyses were performed to examine the levels of signaling pathway components. Results RES supplementation decreased the inflammatory cytokine levels, improved the cardiac function, and ameliorated atrial interstitial fibrosis in the rats with AMI. Furthermore, RES supplementation inhibited NLRP3 inflammasome activity, decreased the TGF-β1 production, and downregulated the p-SMAD2/SMAD2 expression in the heart. Conclusion RES shows notable cardioprotective effects in a rat model of AMI; the possible mechanisms underlying these effects may involve the improvement of cardiac function and atrial interstitial fibrosis via the RES-mediated suppression of NLRP3 inflammasome activity and inhibition of the TGF-β1/SMAD2 signaling pathway in the heart.

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Inhaled NO prevents hyperoxia-induced white matter damage in neonatal rats

Experimental Neurology ◽

10.1016/j.expneurol.2013.11.025 ◽

2014 ◽

Vol 252 ◽

pp. 114-123 ◽

Cited By ~ 22

Author(s):

Hoa Pham ◽

Gaelle Vottier ◽

Julien Pansiot ◽

Sy Duong-Quy ◽

Bieke Bollen ◽

...

Keyword(s):

White Matter ◽

Neonatal Rats ◽

White Matter Damage ◽

Inhaled No

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Impact of inhaled nitric oxide on white matter damage in growth-restricted neonatal rats

Pediatric Research ◽

10.1038/pr.2015.4 ◽

2015 ◽

Vol 77 (4) ◽

pp. 563-569 ◽

Cited By ~ 20

Author(s):

Hoa Pham ◽

An Phan Duy ◽

Julien Pansiot ◽

Bieke Bollen ◽

Jorge Gallego ◽

...

Keyword(s):

Nitric Oxide ◽

White Matter ◽

Inhaled Nitric Oxide ◽

Neonatal Rats ◽

White Matter Damage

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The neuroprotective effects of xenon on neonatal rats with white matter damage by regulating expression of microRNA-210 and HIF-1α

10.21203/rs.2.10732/v2 ◽

2019 ◽

Author(s):

xiangyun yin ◽

Jixiu Zhao ◽

Jian Jiang ◽

Hongmin Xi ◽

Xianghong Li ◽

...

Keyword(s):

White Matter ◽

Expression Level ◽

Neonatal Rats ◽

White Matter Damage ◽

Neuroprotective Effects ◽

Group A ◽

Group B ◽

Group D ◽

Time Point ◽

Brain Tissues

Abstract Background: White matter damage is a leading cause of acute mortality and chronic morbidity in preterm birth. Xenon is a general anesthetic with neuroprotective effects. We aimed to reveal the molecular basis and neuroprotective mechanism of Xe intervention in treating white matter damage by detecting the expression level of miR-210 and HIF-1α in brain tissues of 3-day-old neonatal rats. Methods: Three-day-old SD rats were randomly divided into sham group (Group A, n=24), LPS +HI group (Group B, n=24) and LPS+HI+Xe group (n=72). LPS+HI+Xe group was given Xenon gas inhalation for three hours after treatment of HI at 0h,2h,and 5h,and divided into three subgroups C,D,and E randomly. We investigated the WMD by performing TUNEL and hematoxylin and eosin (HE) staining and examining the expression of miR-210and HIF-1α in brain tissues via RT-PCR and western blot. Results: Our study shows that the brain tissues of neonatal rat which stained by HE were pale, structure loosen, and psychosis along with apoptosis in group B, Xe treatment improved histological alterations and decreased the number of apoptotic cells in group C . The expression level of miR-210 increased significantly at all time points in group B compared to group A (p<0.05),While that was significantly lower at 0h and 48h than that of group C(p<0.05).Compared with group C,the expression of miR-210 in group D and group E decreased significantly at 0h, 24h and 48h (p<0.05).The level of HIF-1α protein in group B was significantly higher than that of group A at each time point, while significantly lower than that of group C at each time point and that of group D and E at 0h, 24h and 72h (p<0.05).Compared with group C and group D,the expression level of HIF-1α protein decreased significantly at 24h in group E (p<0.05). Conclusions: These results demonstrate that the expression of HIF-1α and miR-210 increased in periventricular tissues and Xe could relieve the white matter damage by up-regulating the expression of HIF-1α and its target gene miR-210.The Xe therapeutic time window was within 5 hours after intervention, the sooner the better. Keywords: premature birth, Xenon, microRNA-210, HIF-1α, white matter damage

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