scholarly journals Effects of hypoxia ischemia on caspase-3 expression and neuronal apoptosis in the brain of neonatal mice

2019 ◽  
Author(s):  
Changbo Deng ◽  
Juan Li ◽  
Luyi Li ◽  
Fengjie Sun ◽  
Jiqing Xie
Keyword(s):  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neonatal Mice ◽  
Hypoxia Ischemia ◽  
The Brain

scholarly journals Sugammadex-Enhanced Neuronal Apoptosis following Neonatal Sevoflurane Exposure in Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Maiko Satomoto ◽  
Zhongliang Sun ◽  
Yushi U. Adachi ◽  
Koshi Makita
Keyword(s):  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuronal Damage ◽  
Intraperitoneal Administration ◽  
Binding Agent ◽  
Learning Deficits ◽  
Neonatal Mice ◽  
Transmission Electron ◽  
Pass Through ◽  
The Brain

In rodents, neonatal sevoflurane exposure induces neonatal apoptosis in the brain and results in learning deficits. Sugammadex is a new selective neuromuscular blockade (NMB) binding agent that anesthesiologists can use to achieve immediate reversal of an NMB with few side effects. Given its molecular weight of 2178, sugammadex is thought to be unable to pass through the blood brain barrier (BBB). Volatile anesthetics can influence BBB opening and integrity. Therefore, we investigated whether the intraperitoneal administration of sugammadex could exacerbate neuronal damage following neonatal 2% sevoflurane exposure via changes in BBB integrity. Cleaved caspase-3 immunoblotting was used to detect apoptosis, and the ultrastructure of the BBB was examined by transmission electron microscopy. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice. Sugammadex alone without sevoflurane did not induce apoptosis. The coadministration of sugammadex with sevoflurane to neonatal mice caused a significant increase (150%) in neuroapoptosis in the brain compared with 2% sevoflurane. In neonatal anesthesia, sugammadex could influence neurotoxicity together with sevoflurane. Exposure to 2% sevoflurane for 6 h resulted in BBB ultrastructural abnormalities in the hippocampus of neonatal mice.

scholarly journals Early Upregulation of NLRP3 in the Brain of Neonatal Mice Exposed to Hypoxia-Ischemia: No Early Neuroprotective Effects of NLRP3 Deficiency

Neonatology ◽  
2015 ◽  
Vol 108 (3) ◽  
pp. 211-219 ◽  
Author(s):  
Martin Bogale Ystgaard ◽  
Yngve Sejersted ◽  
Else Marit Løberg ◽  
Egil Lien ◽  
Arne Yndestad ◽  
...  
Keyword(s):  
Neuroprotective Effects ◽  
Neonatal Mice ◽  
Hypoxia Ischemia ◽  
The Brain

scholarly journals Desoxyrhapontigenin attenuates neuronal apoptosis in an isoflurane-induced neuronal injury model by modulating the TLR-4/cyclin B1/Sirt-1 pathway

AMB Express ◽  
2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Feng Liang ◽  
Xin Fu ◽  
Yunpengfei Li ◽  
Fanglei Han
Keyword(s):  
Oxidative Stress ◽  
Cognitive Function ◽  
Protein Expression ◽  
Protective Effect ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuronal Injury ◽  
Cyclin B1 ◽  
The Brain ◽  
And Oxidative Stress

Abstract This study investigated the protective effect of desoxyrhapontigenin (DOP) against isoflurane (ISF)-induced neuronal injury in rats. Neuronal injury was induced in pups by exposing them to 0.75% ISF on postnatal day 7 with 30% oxygen for 6 h. The pups were treated with DOP 10 mg/kg, i.p., for 21 days after ISF exposure. The protective effect of DOP was estimated by assessing cognitive function using the neurological score and the Morris water maze. Neuronal apoptosis was assessed in the hippocampus using the TUNEL assay, and protein expression of caspase-3, Bax, and Bcl-2 was measured by Western blotting. The levels of cytokines and oxidative stress parameters were assessed by ELISA. Western blotting and RT-PCR were performed to measure the expression of NF-kB, TLR-4, Sirt-1, and cyclin B1 protein in the brain. The cognitive function and neurological function scores were improved in the DOP group compared with the ISF group. Moreover, DOP treatment reduced the number of TUNEL-positive cells and the expression of caspase-3, Bax, and Bcl-2 protein in the brains of rats with neuronal injury. The levels of mediators of inflammation and oxidative stress were reduced in the brain tissue of the DOP group. Treatment with DOP attenuated the protein expression of TLR-4, NF-kB, cyclin B1, and Sirt-1 in the brain tissue of rats with neuronal injury. In conclusion, DOP ameliorates neuronal apoptosis and improves cognitive function in rats with ISF-induced neuronal injury. Moreover, DOP treatment can prevent neuronal injury by regulating the TLR-4/cyclin B1/Sirt-1 pathway.

scholarly journals PO-274 Photobiomodulation Preconditioning Prevents Hypoxia-ischemia Induced Dyscinesia in a Neonatal Rat Model

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Luodan Yang ◽  
Chongyun Wu ◽  
Guangcong Peng ◽  
Mengyun Xiao ◽  
Quanguang Zhang
Keyword(s):  
Cytochrome C ◽  
Rat Model ◽  
Neuronal Apoptosis ◽  
Mitochondrial Dynamics ◽  
Neonatal Rat ◽  
Mitochondrial Fragmentation ◽  
Cytochrome C Release ◽  
Hypoxia Ischemia ◽  
The Brain ◽  
Neonatal Rat Model

Objective Neonatal hypoxia-ischemia (HI) injury caused by oxygen deprivation is the most common cause of severe neurologic deficits and dyscinesia in neonates. The work was designed to evaluate the preventative effect of photobiomodulation (PBM) preconditioning on HI-induced Dyscinesia in a Neonatal Rat Model, and its underlying mechanism of PBM action on brain damage in a HI model in neonatal rats. Methods 10-day-old neonatal Sprague-Dawley rats were randomly divided into 3 groups: (a) control group (animals without ligation); (b) HI group (HI animal with PBM pretreatment); (c) PBM group (HI animal with PBM pretreatment). The hanging wire test and cylinder test were conducted to evaluate the the strength and asymmetry of left (contralateral) paw usage, respectively. The volume shrinkage of the brain was analyzed on postnatal day 29. The neuronal loss, mitochondrial dynamics, mitochondrial fragmentation, cytochrome c release, neuronal apoptosis, dendritic and synaptic injury in hippocampus were tested using the brain collected on postnatal day 16. Results PBM preconditioning significantly attenuated motor function impairment, volume shrinkage, neuron loss, dendritic and synaptic injury after HI. Further mechanistic investigation showed that PBM preconditioning effectively restore HI-induced mitochondrial dynamic changes and inhibit mitochondrial fragmentation, accompanied by a robust suppression of cytochrome c release, and prevention of neuronal apoptosis by inhibition of caspase activation. Conclusions PBM preconditioning can prevent HI induced dyscinesia and brain injury by maintaining mitochondrial dynamics and inhibiting mitochondrial apoptotic pathway.  

Abstract 16: Spatiotemporally-Controlled Ultrasound-Triggered Release of Nitric Oxide Using Nano Au-Polymersomes/S-Nitrosoglutathione Mitigates Post-Resuscitation Cerebral Vasoconstriction and Neuronal Apoptosis via Reciprocating Akt-eNOS-NO Signaling

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Wei-Tien Chang ◽  
Woan-Yi Wang ◽  
Min-Hsuan Hsu ◽  
Po-Tsung Kao ◽  
Chih-Hung Wang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Brain Perfusion ◽  
Tissue Perfusion ◽  
Triggered Release ◽  
Cerebral Vasoconstriction ◽  
No Release ◽  
No Signaling ◽  
The Brain

Introduction: Cerebral vasoconstriction in the post-resuscitation phase worsens neurological outcome. Nitric oxide (NO) plays important roles mediating vasodilatation and anti-apoptotic protection. We therefore designed an Au-polymersomes/S-nitrosoglutathione (Au-PLGA/GSNO) nanoparticle that can be triggered by ultrasound (US) to release NO, and investigated its roles in mitigating cerebral vasoconstriction and neuronal apoptosis post-CPR. Hypothesis: Spatiotemporally controlled, US-triggered NO release by Au-PLGA/GSNO improves post-CPR cerebral perfusion and confers anti-apoptotic neuroprotection. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, Au-PLGA/GSNO (7500 PPM, 0.4 ml) was infused with simultaneous US (1 MHz) stimulation at the brain 10 min after ROSC. Brain tissue perfusion was continuously recorded by OxyFLO probe and cerebral vasculature videoed by CytoCam. The blood was sampled 2 h post-CPR for measurement of nitrate/nitrite, and the brain harvested for measurement of casepase-3, endothelial NO synthase (eNOS) and protein kinase B (Akt). In a subgroup the brain was harvested at 24 h for TUNEL stain. Results: After CPR, marked cerebral vasoconstriction was noted on CytoCam while brain perfusion significantly reduced to ~0.5 folds that of baseline. After Au-PLGA/GSNO infusion and US stimulation, cerebral vasoconstriction was ameliorated and the brain perfusion significantly enhanced ( P < 0.05 vs. CPR control). The plasma NO indicated by nitrate/nitrite 2 h post-CPR was significantly increased ( P < 0.01) while cleaved caspase-3/caspase-3 of the brain markedly reduced ( P < 0.001). TUNEL stain of the hippocampus CA1 and CA3 regions were also remarkably abrogated, suggesting anti-apoptotic neuroprotection. Specifically, the phosphorylated (p)-eNOS/eNOS and p-Akt/Akt were also increased ( P < 0.01 and 0.001, respectively), indicating reciprocating activation of Akt-eNOS signaling upstream of NO. Conclusion: Spatiotemporally controlled US-triggered NO release by Au-PLGA/GSNO mitigates cerebral vasoconstriction, improves brain perfusion and confers anti-apoptotic neuroprotection post-CPR via reciprocating Akt-eNOS-NO signaling.

scholarly journals Influence of miR-1 on Nerve Cell Apoptosis in Rats with Cerebral Stroke via Regulating ERK Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Yuanding Jiang ◽  
Tao Wang ◽  
Jian He ◽  
Quan Liao ◽  
Jingjing Wang
Keyword(s):  
Infarct Size ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Sham Group ◽  
Cerebral Infarct ◽  
Erk Signaling ◽  
Model Group ◽  
Protein Levels ◽  
The Brain ◽  
Brain Tissues

To explore the effect of miR-1 on neuronal apoptosis in rats with stroke through the ERK signaling pathway. Methods. Forty male rats (180-220 g) were selected and randomly divided into the sham, model, miR-1 inhibitor, and miR-1 mimic groups (10 rats per group) by average body weight. Cerebral ischemia/reperfusion (I/R) models were established using a modified middle cerebral artery wire thrombosis (MCAO) method in rats in the model group, miR-1 inhibitor group, and miR-1 mimic group. After the successful model establishment, the miR-1inhibitor group and miR-1 mimic group were intravenously injected with miR-1 inhibitor and miR-1 mimic, respectively, once a day for 3 days. The sham and model groups were given the same dose of normal saline. TTC staining was applied to detect the cerebral infarct size and calculate the infarct volume. Histopathological changes in the hippocampus of rat brains were observed by HE staining. Flow cytometry was used to detect neuronal apoptosis in rat brains. The mRNA expressions of miR-1, ERK1/2, Bcl-2, and Bax in rat brain tissues were determined by QRT PCR, and the protein levels of ERK1/2, Bcl-2, Bax, and caspase-3 were determined by Western blot analysis. Results. Compared with the sham group, the neurological impairment score, cerebral infarct size, and volume of rats in the model group were significantly increased ( p < 0.05 ). Compared with the model group, the neurological impairment score, cerebral infarct size, and volume were significantly increased in the miR-1 mimic group and significantly decreased in the miR-1 inhibitor group ( p < 0.05 ). In the model group, the hippocampal tissue of rats had malaligned cells, neuron cell atrophy became smaller, the intercellular spaces became larger, and vacuoles appeared. Compared with the model group, the miR-1 inhibitor group could effectively alleviate the pathological changes in the hippocampus, and the miR-1 mimic group could significantly add to the pathological changes in the rat hippocampus. Compared with the sham group, the mRNA expression of miR-1 and Bax in the brain of model rats increased significantly ( p < 0.05 ), and the mRNA expression of ERK1/2 decreased significantly; Compared with the model group, the miR-1 and Bax mRNA expressions in the brain tissues of rats in the miR-1 inhibitor group were significantly decreased, the ERK1/2 and bcl-2 mRNA expressions were significantly increased, and the miR-1 and Bax mRNA expressions in the brain tissues of rats in the miR-1 inhibitor group were significantly decreased, and the Bcl-2 mRNA expression was significantly increased ( p < 0.05 ). Compared with the sham group, neuronal apoptosis was increased in the brain tissues of rats in the model group and miR-1 mimic group. Compared with the model group, neuronal apoptosis was decreased in the brain tissues of rats in the miR-1 inhibitor group. Compared with the sham group, the ERK1/2 proteins in the model group were significantly decreased, the Bcl-2, Bax, and caspase-3 proteins were significantly increased, and the ERK1/2, Bcl-2, Bax, and caspase-3 proteins in the miR-1 inhibitor group and miR-1 mimic group were significantly increased. Compared with the model group, the protein levels of ERK1/2 and Bcl-2 in the miR-1 inhibitor group were significantly increased, the proteins of Bax and caspase-3 were significantly decreased, and the protein levels of ERK1/2 and Bcl-2 in the miR-1 inhibitor group were significantly increased ( p < 0.05 ). Conclusions. miR-1 can interfere with neuronal apoptosis in rats with stroke through the ERK signaling pathway.

Postischemic Hyperthermia Induced Caspase-3 Activation in the Newborn Rat Brain after Hypoxia-Ischemia and Exacerbated the Brain Damage

Neonatology ◽  
2003 ◽  
Vol 84 (2) ◽  
pp. 164-171 ◽  
Author(s):  
Hirotsugu Fukuda ◽  
Takuji Tomimatsu ◽  
Takeshi Kanagawa ◽  
Junwu Mu ◽  
Masatomo Kohzuki ◽  
...  
Keyword(s):  
Rat Brain ◽  
Brain Damage ◽  
Caspase 3 ◽  
Newborn Rat ◽  
Hypoxia Ischemia ◽  
The Brain

Abstract 103: Propofol Infusion in the Early Post-Cardiac Arrest Phase Improves Cerebral Perfusion and Confers Anti-Apoptotic Neuroprotection via Akt-eNOS-NO Signaling

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Wei-Tien Chang ◽  
Min-Hsuan Hsu ◽  
Woan-Yi Wang ◽  
Chunpei Lee ◽  
Chih-Hung Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cerebral Perfusion ◽  
Neuronal Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Temperature Management ◽  
Target Temperature Management ◽  
Arterial Blood ◽  
No Signaling ◽  
The Brain

Introduction: Neurological outcome after cardiac arrest (CA) and CPR is usually unsatisfactory even in this era of target temperature management (TTM). Propofol is not only a useful sedative drug for TTM but confers neuroprotective effect. We previously showed that propofol combined with TTM improves survival in patients resuscitated from CA. In this study we aimed to explore the underlying mechanism focusing on cerebrovascular circulation and anti-apoptosis signaling. Hypothesis: Infusion of propofol in the early post-CA phase improves cerebral perfusion and mitigates neuronal apoptosis via Akt-eNOS signaling. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, propofol infusion (20 mg/kg/h) was instituted after return of spontaneous circulation (ROSC) and continued in the first 2 h. Hemodynamics were monitored and the cerebral perfusion was continuously recorded by OxyFLO probe. The arterial blood was regularly sampled for measurement of reactive oxygen species (ROS, chemiluminescence method) and NO (demonstrated by nitrate/nitrite). Two hours after ROSC, the brain was harvested for measurement of casepase-3, endothelial NO synthase (eNOS) and protein kinase B (Akt). Results: After CA and CPR, the cerebral perfusion was significantly reduced to ~0.5 folds that of baseline. With the infusion of propofol, the cerebral perfusion was significantly increased from the beginning after ROSC ( P < 0.01 vs. CPR control). The plasma NO indicated by nitrate/nitrite 2 h post-CPR was significantly increased ( P < 0.01) while ROS abrogated ( P < 0.05). The cleaved caspase-3/caspase-3 of the brain was markedly reduced ( P < 0.001), suggesting anti-apoptotic neuroprotection. When exploring the mechanism, the phosphorylated (p)-eNOS/eNOS and p-Akt/Akt were significantly increased (both P < 0.001), indicating activation of Akt-eNOS-NO signaling. Conclusions: Infusion of propofol in the early post-CA phase reduces oxidative stress, improves cerebral perfusion, and ameliorates neuronal apoptosis. The protection is, at least in part, mediated via activation of Akt-eNOS-NO signaling.

scholarly journals Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats’ Brain and Heart

2021 ◽  
Vol 22 (13) ◽  
pp. 6839
Author(s):  
Ali H. El-Far ◽  
Yaser H. A. Elewa ◽  
Elsayeda-Zeinab A. Abdelfattah ◽  
Abdel-Wahab A. Alsenosy ◽  
Mustafa S. Atta ◽  
...  
Keyword(s):  
Animal Models ◽  
Calcium Binding ◽  
Caspase 3 ◽  
Combination Group ◽  
Preventive Effect ◽  
Group Data ◽  
Adapter Molecule ◽  
The Brain ◽  
Bcl2 Expression

D-galactose (D-gal) administration causes oxidative disorder and is widely utilized in aging animal models. Therefore, we subcutaneously injected D-gal at 200 mg/kg BW dose to assess the potential preventive effect of thymoquinone (TQ) and curcumin (Cur) against the oxidative alterations induced by D-gal. Other than the control, vehicle, and D-gal groups, the TQ and Cur treated groups were orally supplemented at 20 mg/kg BW of each alone or combined. TQ and Cur effectively suppressed the oxidative alterations induced by D-gal in brain and heart tissues. The TQ and Cur combination significantly decreased the elevated necrosis in the brain and heart by D-gal. It significantly reduced brain caspase 3, calbindin, and calcium-binding adapter molecule 1 (IBA1), heart caspase 3, and BCL2. Expression of mRNA of the brain and heart TP53, p21, Bax, and CASP-3 were significantly downregulated in the TQ and Cur combination group along with upregulation of BCL2 in comparison with the D-gal group. Data suggested that the TQ and Cur combination is a promising approach in aging prevention.

scholarly journals Genistein reduced the neural apoptosis in the brain of ovariectomised rats by modulating mitochondrial oxidative stress

2010 ◽  
Vol 104 (9) ◽  
pp. 1297-1303 ◽  
Author(s):  
Yan-Hong Huang ◽  
Qing-Hong Zhang
Keyword(s):  
Oxidative Stress ◽  
Learning And Memory ◽  
Caspase 3 ◽  
Visual Learning ◽  
Morris Water Maze Test ◽  
High Dose ◽  
Dependent Manner ◽  
Ovx Rats ◽  
Neural Apoptosis ◽  
The Brain

The present study was undertaken to investigate the antioxidant effect of chronic ingestion of genistein (Gen) against neural death in the brain of ovariectomised (Ovx) rats. The rats were randomly divided into five groups, i.e. sham-operated (sham), Ovx-only, Ovx with 17β-oestradiol, Ovx with low (15 mg/kg) and high (30 mg/kg) doses of Gen (Gen-L and Gen-H), and were orally administered daily with drugs or vehicle for 6 weeks. The learning and memory abilities were measured by Morris water maze test. Oxidative damages in the brain were evaluated by the level of superoxide dismutase (SOD), malondialdehyde (MDA) and monoamine oxidase (MAO) activities. Neural apoptosis was shown by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) staining and caspase-3 activity. In the visual learning and memory test, there were no significant differences among the population means of the five groups. While in the probe trial test, the Gen-L group instead of the Gen-H group exhibited reduced escape latency and increased memory frequency than the Ovx group. Although both doses of Gen could reduce acetylcholinesterase activity, only a low dose of Gen could diminish MDA activity significantly in frontal cortex and enhance SOD content in the hippocampus. In contrast, MAO content was decreased in the cortex by either dose of Gen, while in the hippocampus, only a high dose of Gen appeared to be effective. Interestingly, Gen at both the doses could attenuate the increased number of TUNEL-positive neurons and caspase-3 activity in Ovx rats. These results suggest that Gen confers protection against Ovx-induced neurodegeneration by attenuating oxidative stress, lipid peroxidation and the mitochondria-mediated apoptotic pathway in a region- and dose-dependent manner.

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