Effect of hyperbaric oxygen on apoptosis in neonatal hypoxia-ischemia rat model

2003 ◽  
Vol 95 (5) ◽  
pp. 2072-2080 ◽  
Author(s):  
John W. Calvert ◽  
Changman Zhou ◽  
Anil Nanda ◽  
John H. Zhang
Keyword(s):  
Hyperbaric Oxygen ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Parp Cleavage ◽  
Artery Ligation ◽  
Neonatal Hypoxia ◽  
Rat Pups ◽  
Hypoxia Ischemia ◽  
Expression And Activity

We have previously demonstrated that a transient exposure to hyperbaric oxygen (HBO) attenuated the neuronal injury after neonatal hypoxia-ischemia. This study was undertaken to determine whether HBO offers this neuroprotection by reducing apoptosis in injured brain tissue. Seven-day-old rat pups were subjected to unilateral carotid artery ligation followed by 2 h of hypoxia (8% oxygen). Apoptotic cell death was examined in the injured cortex and hippocampus tissue. Caspase-3 expression and activity increased at 18 and 24 h after the hypoxia-ischemia insult. At 18-48 h, poly(ADP-ribose) polymerase (PARP) cleavage occurred, which reduced the band at 116 kDa and enhanced the band at 85 kDa. There was a time-dependent increase in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL)-positive cells. A single HBO treatment (100% oxygen, 3 ATA for 1 h) 1 h after hypoxia reduced the enhanced caspase-3 expression and activity, attenuated the PARP cleavage, and decreased the number of TUNEL-positive cells observed in the cortex and hippocampus. These results suggest that the neuroprotective effect of HBO is at least partially mediated by the reduction of apoptosis.

scholarly journals Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia

Autophagy ◽  
2010 ◽  
Vol 6 (3) ◽  
pp. 366-377 ◽  
Author(s):  
Silvia Carloni ◽  
Silvia Girelli ◽  
Claudia Scopa ◽  
Giuseppe Buonocore ◽  
Mariangela Longini ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

Abstract WP62: Enhanced Neuroprotection of Normobaric Oxygenation with Ethanol Conferred by Apoptosis Reduction in Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Sweena Parmar ◽  
Xiaokun Geng ◽  
Changya Peng ◽  
Murali Guthikonda ◽  
Yuchuan Ding
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Apoptotic Cell Death ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Apoptotic Proteins

Objectives: Normobaric oxygenation (NBO) has been shown to provide neuroprotection in vivo and in vitro . Yet, a recent Phase 2 clinical trial investigating NBO therapy in acute ischemic stroke was terminated due to questionable therapeutic benefit. NBO therapy alone may be insufficient to produce improved outcomes. In our recent study, we demonstrated a strong neuroprotective effect of ethanol at a dose of 1.5 g/kg (equivalent to the human legal driving limit). In this study, we sought to identify whether low-dose ethanol administration enhances the neuroprotection offered by NBO and whether combined administration of NBO with ethanol is associated with reduced apoptosis. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. Ischemic animals received either an intraperitoneal injection of 1.0 g/kg ethanol, 2 h of 100% NBO, or both ethanol and NBO. The Cell Death Detection ELISA Assay (Roche) was performed to determine apoptotic cell death at 24 h after reperfusion. Levels of pro-apoptotic (Caspase-3, Bcl-2-associated X-BAX, and Apoptosis-Inducing Factor-AIF) and anti-apoptotic proteins (Bcl-2 and Bcl-xL) were determined by Western blot analysis at 3 and 24 h after reperfusion. Results: As expected, untreated ischemic rats had the highest apoptotic cell death. Combined NBO/ethanol therapy decreased cell death by 48%, as compared to 29% with ethanol and 22% with NBO. Similarly, combined NBO/ethanol therapy promoted the greatest expression of anti-apoptotic factors and the lowest expression of pro-apoptotic proteins at 3 h after reperfusion. This effect was maintained at 24 h and even more pronounced for AIF and Caspase-3. Conclusions: Given singularly, NBO and ethanol improved the degree of cell death, decreased the expression of pro-apoptotic proteins, and increased the expression of anti-apoptotic proteins. Yet, when administered together, their effects largely compounded. These results suggest a synergistic neuroprotection offered by NBO with ethanol, which may be attributed at least in part to their shared role in modulating neuronal apoptosis.

Experimental neonatal hypoxia ischemia causes long lasting changes of oxidative stress parameters in the hippocampus and the spleen

2018 ◽  
Vol 46 (4) ◽  
pp. 433-439 ◽  
Author(s):  
Felipe Kawa Odorcyk ◽  
Janaína Kolling ◽  
Eduardo Farias Sanches ◽  
Angela T.S. Wyse ◽  
Carlos Alexandre Netto
Keyword(s):  
Oxidative Stress ◽  
Wistar Rat ◽  
Mortality And Morbidity ◽  
Neonatal Hypoxia ◽  
Oxidative Stress Parameters ◽  
Rat Pups ◽  
Hypoxia Ischemia ◽  
Anti Oxidant ◽  
Enzyme Superoxide Dismutase ◽  
Stress Parameters

Abstract Neonatal hypoxia ischemia (HI) is the main cause of mortality and morbidity in newborns. The mechanisms involved in its progression start immediately and persist for several days. Oxidative stress and inflammation are determinant factors of the severity of the final lesion. The spleen plays a major part in the inflammatory response to HI. This study assessed the temporal progression of HI-induced alterations in oxidative stress parameters in the hippocampus, the most affected brain structure, and in the spleen. HI was induced in Wistar rat pups in post-natal day 7. Production of reactive oxygen species (ROS), and the activity of the anti oxidant enzyme superoxide dismutase and catalase were assessed 24 h, 96 h and 38 days post-HI. Interestingly, both structures showed a similar pattern, with few alterations in the production of ROS species up to 96 h often combined with an increased activity of the anti oxidant enzymes. However, 38 days after the injury, ROS were at the highest in both structures, coupled with a decrease in the activity of the enzymes. Altogether, present results suggest that HI causes long lasting alterations in the hippocampus as well as in the spleen, suggesting a possible target for delayed treatments for HI.

Sildenafil Improves Brain Injury Recovery following Term Neonatal Hypoxia-Ischemia in Male Rat Pups

2016 ◽  
Vol 38 (4) ◽  
pp. 251-263 ◽  
Author(s):  
Armin Yazdani ◽  
Zehra Khoja ◽  
Aaron Johnstone ◽  
Laura Dale ◽  
Emmanouil Rampakakis ◽  
...  
Keyword(s):  
Brain Injury ◽  
Gait Analysis ◽  
Left Hemisphere ◽  
Neurological Deficits ◽  
Male Rat ◽  
Boundary Zone ◽  
Neonatal Hypoxia ◽  
Rat Pups ◽  
Hypoxia Ischemia ◽  
Injury Recovery

Term asphyxiated newborns remain at risk of developing brain injury despite available neuropreventive therapies such as hypothermia. Neurorestorative treatments may be an alternative. This study investigated the effect of sildenafil on brain injury induced by neonatal hypoxia-ischemia (HI) at term-equivalent age. Neonatal HI was induced in male Long-Evans rat pups at postnatal day 10 (P10) by left common carotid ligation followed by a 2-hour exposure to 8% oxygen; sham-operated rat pups served as the control. Both groups were randomized to oral sildenafil or vehicle twice daily for 7 consecutive days. Gait analysis was performed on P27. At P30, the rats were sacrificed, and their brains were extracted. The surfaces of both hemispheres were measured on hematoxylin and eosin-stained brain sections. Mature neurons and endothelial cells were quantified near the infarct boundary zone using immunohistochemistry. HI caused significant gait impairment and a reduction in the size of the left hemisphere. Treatment with sildenafil led to an improvement in the neurological deficits as measured by gait analysis, as well as an improvement in the size of the left hemisphere. Sildenafil, especially at higher doses, also caused a significant increase in the number of neurons near the infarct boundary zone. In conclusion, sildenafil administered after neonatal HI may improve brain injury recovery by promoting neuronal populations.

scholarly journals Does Levetiracetam Administration Prevent Cardiac Damage in Adulthood Rats Following Neonatal Hypoxia/Ischemia-Induced Brain Injury?

Medicina ◽  
2018 ◽  
Vol 54 (2) ◽  
pp. 12 ◽  
Author(s):  
Serkan Gurgul ◽  
Belgin Buyukakilli ◽  
Mustafa Komur ◽  
Cetin Okuyaz ◽  
Ebru Balli ◽  
...  
Keyword(s):  
Neonatal Period ◽  
Myocardial Damage ◽  
Control Group ◽  
Protective Effects ◽  
Ventricular Contractility ◽  
Cardiac Damage ◽  
Artery Ligation ◽  
Neuroprotective Effects ◽  
Rat Pups ◽  
Hypoxia Ischemia

Cardiovascular abnormalities are widespread when a newborn is exposed to a hypoxic-ischemic injury in the neonatal period. Although the neuroprotective effects of levetiracetam (LEV) have been reported after hypoxia, the cardioprotective effects of LEV have not been documented. Therefore, we aimed to investigate whether levetiracetam (LEV) has a protective effect on cardiac-contractility and ultrastructure of heart muscle in rats exposed to hypoxia-ischemia (HI) during the neonatal period. A total of 49 seven-day-old rat pups were separated into four groups. For HI induction, a combination of right common carotid artery ligation with 8% oxygen in seven-day-old rat pups for 2 h was performed for saline, LEV100, and LEV200 groups. Just after hypoxia, LEV100 and LEV200 groups were administered with 100 mg/kg and 200 mg/kg of LEV, respectively. The arteries of rats in the control group were only detected; no ligation or hypoxia was performed. At the end of the 16th week after HI, cardiac mechanograms were recorded, and samples of tissue were explored by electronmicroscopy.While ventricular contractility in the control group was similar to LEV100, there were significant decreases in both saline and LEV200 groups (p < 0.05). Although ventricular contractile duration of the control and saline groups was found to be similar, durations in the LEV100 and LEV200 groups were significantly higher (p < 0.05). After HI, mitochondrial damage and ultrastructural deteriorative alterations in ventricles and atriums of the LEV-administered groups were significantly less severe than the saline group. The present study showed that neonatal HI caused long-term cardiac dysfunction and ultrastructural deteriorations in cardiac muscles. LEV administration just after HI might possess some protective effects against myocardial damage and contractility.

scholarly journals Differential activation of c-fos and caspase-3 in hippocampal neuron subpopulations following neonatal hypoxia-ischemia

2008 ◽  
Vol 86 (5) ◽  
pp. 1115-1124 ◽  
Author(s):  
Jayne M. Ness ◽  
Cary R. Harvey ◽  
Jason D. Washington ◽  
Kevin A. Roth ◽  
Steven L. Carroll ◽  
...  
Keyword(s):  
Hippocampal Neuron ◽  
Caspase 3 ◽  
Differential Activation ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

scholarly journals Partial Neuroprotective Effect of Pretreatment with Tanshinone IIA on Neonatal Hypoxia-Ischemia Brain Damage

2005 ◽  
Vol 58 (4) ◽  
pp. 784-790 ◽  
Author(s):  
Wen Jie Xia ◽  
Mo Yang ◽  
Tai Fai Fok ◽  
Karen Li ◽  
Wood Yee Chan ◽  
...  
Keyword(s):  
Brain Damage ◽  
Neuroprotective Effect ◽  
Tanshinone Iia ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

scholarly journals Global Gene Expression in the Immature Brain after Hypoxia-Ischemia

2004 ◽  
Vol 24 (12) ◽  
pp. 1317-1332 ◽  
Author(s):  
Hedtjärn Maj ◽  
Carina Mallard ◽  
Saskia Eklind ◽  
Katarina Gustafson-Brywe ◽  
Henrik Hagberg
Keyword(s):  
Global Gene Expression ◽  
Differentially Expressed ◽  
Global Changes ◽  
Artery Ligation ◽  
Oligonucleotide Arrays ◽  
Genomic Changes ◽  
Neonatal Hypoxia ◽  
Carotid Artery Ligation ◽  
New Genes ◽  
Hypoxia Ischemia

Ischemia induces a complex response of differentially expressed genes in the brain. In order to understand the specific mechanisms of injury in the developing brain, it is important to obtain information on global changes in the transcriptome after neonatal hypoxia-ischemia. In this study, oligonucleotide arrays were used to investigate genomic changes at 2, 8, 24, and 72 hours after neonatal hypoxia-ischemia, which was induced in 9-day-old mice by left carotid artery ligation followed by hypoxia (10% O2). In total, 343 genes were differentially expressed in cortex, hippocampus, thalamus, and striatum 2 to 72 hours after hypoxia-ischemia, when comparing ipsilateral with contralateral hemispheres and with controls, using the significance analysis for microarrays. A total of 283 genes were upregulated and 60 were downregulated, and 94% of the genes had not previously been shown after neonatal hypoxia-ischemia. Genes related to transcription factors and metabolism had mostly upregulated transcripts, whereas most downregulated genes belonged to the categories of ion and vesicular transport and signal transduction. Genes involved in transcription, stress, and apoptosis were induced early after the insult, and many new genes that may play important roles in the pathophysiology of neonatal hypoxiaischemia were identified.

scholarly journals Synergistic Activation of Caspase-3 by m-Calpain after Neonatal Hypoxia-Ischemia

2000 ◽  
Vol 276 (13) ◽  
pp. 10191-10198 ◽  
Author(s):  
Klas Blomgren ◽  
Changlian Zhu ◽  
Xiaoyang Wang ◽  
Jan-Olof Karlsson ◽  
Anna-Lena Leverin ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Neonatal Hypoxia ◽  
Synergistic Activation ◽  
Hypoxia Ischemia

BDNF Blocks Caspase-3 Activation in Neonatal Hypoxia–Ischemia

2000 ◽  
Vol 7 (1) ◽  
pp. 38-53 ◽  
Author(s):  
Byung Hee Han ◽  
Anselm D'Costa ◽  
Stephen A. Back ◽  
Maia Parsadanian ◽  
Shilen Patel ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia
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