Neuroprotective effects by hypothermia are mediated through a coordinated suppression of acetyl coa contents leading to a decrease in acetylcholine contents in neonatal hypoxia-ischemia

2017 ◽  
Vol 381 ◽  
pp. 526
Author(s):  
M. Kajimura ◽  
T. Takenouchi ◽  
Y. Sugiura ◽  
T. Hishiki ◽  
T. Matsuura ◽  
...  
Keyword(s):  
Acetyl Coa ◽  
Neuroprotective Effects ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

Neuroprotective effects of hydrogen saline in neonatal hypoxia–ischemia rat model

2009 ◽  
Vol 1256 ◽  
pp. 129-137 ◽  
Author(s):  
Jianmei Cai ◽  
Zhimin Kang ◽  
Kan Liu ◽  
WenWu Liu ◽  
RunPing Li ◽  
...  
Keyword(s):  
Rat Model ◽  
Neuroprotective Effects ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

scholarly journals Neuroprotective Effects of Mitochondria-Targeted Plastoquinone in a Rat Model of Neonatal Hypoxic–Ischemic Brain Injury

Molecules ◽  
2018 ◽  
Vol 23 (8) ◽  
pp. 1871 ◽  
Author(s):  
Denis Silachev ◽  
Egor Plotnikov ◽  
Irina Pevzner ◽  
Ljubava Zorova ◽  
Anastasia Balakireva ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Targeted Delivery ◽  
Cell Damage ◽  
Brain Cell ◽  
Neuroprotective Effects ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia ◽  
Causes Of Mortality ◽  
High Production ◽  
The Brain

Neonatal hypoxia–ischemia is one of the main causes of mortality and disability of newborns. To study the mechanisms of neonatal brain cell damage, we used a model of neonatal hypoxia–ischemia in seven-day-old rats, by annealing of the common carotid artery with subsequent hypoxia of 8% oxygen. We demonstrate that neonatal hypoxia–ischemia causes mitochondrial dysfunction associated with high production of reactive oxygen species, which leads to oxidative stress. Targeted delivery of antioxidants to the mitochondria can be an effective therapeutic approach to treat the deleterious effects of brain hypoxia–ischemia. We explored the neuroprotective properties of the mitochondria-targeted antioxidant SkQR1, which is the conjugate of a plant plastoquinone and a penetrating cation, rhodamine 19. Being introduced before or immediately after hypoxia–ischemia, SkQR1 affords neuroprotection as judged by the diminished brain damage and recovery of long-term neurological functions. Using vital sections of the brain, SkQR1 has been shown to reduce the development of oxidative stress. Thus, the mitochondrial-targeted antioxidant derived from plant plastoquinone can effectively protect the brain of newborns both in pre-ischemic and post-stroke conditions, making it a promising candidate for further clinical studies.

scholarly journals Therapeutic Hypothermia Achieves Neuroprotection via a Decrease in Acetylcholine with a Concurrent Increase in Carnitine in the Neonatal Hypoxia-Ischemia

2015 ◽  
Vol 35 (5) ◽  
pp. 794-805 ◽  
Author(s):  
Toshiki Takenouchi ◽  
Yuki Sugiura ◽  
Takayuki Morikawa ◽  
Tsuyoshi Nakanishi ◽  
Yoshiko Nagahata ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Therapeutic Hypothermia ◽  
Quantitative Imaging ◽  
Imaging Mass Spectrometry ◽  
Brain Regions ◽  
Acetyl Coa ◽  
Neuroprotective Effects ◽  
Neurologic Outcomes ◽  
Hypoxia Ischemia ◽  
The Brain

Although therapeutic hypothermia is known to improve neurologic outcomes after perinatal cerebral hypoxia-ischemia, etiology remains unknown. To decipher the mechanisms whereby hypothermia regulates metabolic dynamics in different brain regions, we used a two-step approach: a metabolomics to target metabolic pathways responding to cooling, and a quantitative imaging mass spectrometry to reveal spatial alterations in targeted metabolites in the brain. Seven-day postnatal rats underwent the permanent ligation of the left common carotid artery followed by exposure to 8% O2 for 2.5 hours. The pups were returned to normoxic conditions at either 38°C or 30°C for 3 hours. The brain metabolic states were rapidly fixed using in situ freezing. The profiling of 107 metabolites showed that hypothermia diminishes the carbon biomass related to acetyl moieties, such as pyruvate and acetyl-CoA; conversely, it increases deacetylated metabolites, such as carnitine and choline. Quantitative imaging mass spectrometry demarcated that hypothermia diminishes the acetylcholine contents specifically in hippocampus and amygdala. Such decreases were associated with an inverse increase in carnitine in the same anatomic regions. These findings imply that hypothermia achieves its neuroprotective effects by mediating the cellular acetylation status through a coordinated suppression of acetyl-CoA, which resides in metabolic junctions of glycolysis, amino-acid catabolism, and ketolysis.

scholarly journals Doxycycline Reduces Cleaved Caspase-3 and Microglial Activation in An Animal Model of Neonatal Hypoxia-Ischemia

2005 ◽  
Vol 25 (3) ◽  
pp. 314-324 ◽  
Author(s):  
Lauren L Jantzie ◽  
Po-Yin Cheung ◽  
Kathryn G Todd
Keyword(s):  
Animal Model ◽  
Microglial Activation ◽  
Time Course ◽  
Caspase 3 ◽  
Hippocampal Formation ◽  
Brain Regions ◽  
Dependent Manner ◽  
Neuroprotective Effects ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

Neonatal hypoxia-ischemia (HI) is a major contributor to many perinatal neurologic disorders and, thus, the search for therapies and effective treatments for the associated brain damage has become increasingly important. The tetracycline derivative, doxycycline (DOXY), has been reported to be neuroprotective in adult animal models of cerebral ischemia. To investigate the putative neuroprotective effects of DOXY in an animal model of neonatal HI, a time-course study was run such that pups received either DOXY (10 mg/kg) or VEH immediately before hypoxia, 1, 2, or 3 hours after HI ( n=6). At 7 days after injury, the pups were euthanized, and the brains were removed and processed for immunohistochemical and Western blot analyses using antibodies against specific markers for neurons, apoptotic markers, microglia, oligodendrocytes, and astrocytes. Results showed that in vulnerable brain regions including the hippocampal formation, thalamus, striatum, cerebral cortex and white matter tracts, DOXY significantly decreased caspase-3 immunoreactivity (a marker of apoptosis), promoted neuronal survival, inhibited microglial activation and reduced reactive astrocytosis compared with VEH-treated HI pups. These effects were found to occur in a time-dependent manner. Taken together, these results strongly suggest that doxycycline has potential as a pharmacological treatment for mild HI in neonates.

scholarly journals Neuroprotective Effects of Diabetes Drugs for the Treatment of Neonatal Hypoxia-Ischemia Encephalopathy

2020 ◽  
Vol 14 ◽  
Author(s):  
Laura Poupon-Bejuit ◽  
Eridan Rocha-Ferreira ◽  
Claire Thornton ◽  
Henrik Hagberg ◽  
Ahad A. Rahim
Keyword(s):  
Neuroprotective Effects ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

scholarly journals Neuroprotective Effect of Maternal Resveratrol Supplementation in a Rat Model of Neonatal Hypoxia-Ischemia

2021 ◽  
Vol 14 ◽  
Author(s):  
Ursule Dumont ◽  
Stéphane Sanchez ◽  
Cendrine Repond ◽  
Marie-Christine Beauvieux ◽  
Jean-François Chateil ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Brain Lesions ◽  
Female Rats ◽  
Neuroprotective Effects ◽  
Western Blots ◽  
Lactate Shuttle ◽  
Pregnant Rat ◽  
Ischemic Event ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

Neonatal hypoxia-ischemia (nHI) is a major cause of death or subsequent disabilities in infants. Hypoxia-ischemia causes brain lesions, which are induced by a strong reduction in oxygen and nutrient supply. Hypothermia is the only validated beneficial intervention, but not all newborns respond to it and today no pharmacological treatment exists. Among possible therapeutic agents to test, trans-resveratrol is an interesting candidate as it has been reported to exhibit neuroprotective effects in some neurodegenerative diseases. This experimental study aimed to investigate a possible neuroprotection by resveratrol in rat nHI, when administered to the pregnant rat female, at a nutritional dose. Several groups of pregnant female rats were studied in which resveratrol was added to drinking water either during the last week of pregnancy, the first week of lactation, or both. Then, 7-day old pups underwent a hypoxic-ischemic event. Pups were followed longitudinally, using both MRI and behavioral testing. Finally, a last group was studied in which breastfeeding females were supplemented 1 week with resveratrol just after the hypoxic-ischemic event of the pups (to test the curative rather than the preventive effect). To decipher the molecular mechanisms of this neuroprotection, RT-qPCR and Western blots were also performed on pup brain samples. Data clearly indicated that when pregnant and/or breastfeeding females were supplemented with resveratrol, hypoxic-ischemic offspring brain lesions were significantly reduced. Moreover, maternal resveratrol supplementation allowed to reverse sensorimotor and cognitive deficits caused by the insult. The best recoveries were observed when resveratrol was administered during both gestation and lactation (2 weeks before the hypoxic-ischemic event in pups). Furthermore, neuroprotection was also observed in the curative group, but only at the latest stages examined. Our hypothesis is that resveratrol, in addition to the well-known neuroprotective benefits via the sirtuin’s pathway (antioxidant properties, inhibition of apoptosis), has an impact on brain metabolism, and more specifically on the astrocyte-neuron lactate shuttle (ANLS) as suggested by RT-qPCR and Western blot data, that contributes to the neuroprotective effects.

scholarly journals Neuronal Damage Induced by Perinatal Asphyxia Is Attenuated by Postinjury Glutaredoxin-2 Administration

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Juan Ignacio Romero ◽  
Mariana Inés Holubiec ◽  
Tamara Logica Tornatore ◽  
Stéphanie Rivière ◽  
Eva-Maria Hanschmann ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Neuronal Damage ◽  
Perinatal Asphyxia ◽  
Ischemia Reperfusion ◽  
Glutamate Excitotoxicity ◽  
Ischemic Damage ◽  
Sprague Dawley ◽  
Neuroprotective Effects ◽  
Neonatal Hypoxia ◽  
Hypoxia Ischemia

The general disruption of redox signaling following an ischemia-reperfusion episode has been proposed as a crucial component in neuronal death and consequently brain damage. Thioredoxin (Trx) family proteins control redox reactions and ensure protein regulation via specific, oxidative posttranslational modifications as part of cellular signaling processes. Trx proteins function in the manifestation, progression, and recovery following hypoxic/ischemic damage. Here, we analyzed the neuroprotective effects of postinjury, exogenous administration of Grx2 and Trx1 in a neonatal hypoxia/ischemia model. P7 Sprague-Dawley rats were subjected to right common carotid ligation or sham surgery, followed by an exposure to nitrogen. 1 h later, animals were injected i.p. with saline solution, 10 mg/kg recombinant Grx2 or Trx1, and euthanized 72 h postinjury. Results showed that Grx2 administration, and to some extent Trx1, attenuated part of the neuronal damage associated with a perinatal hypoxic/ischemic damage, such as glutamate excitotoxicity, axonal integrity, and astrogliosis. Moreover, these treatments also prevented some of the consequences of the induced neural injury, such as the delay of neurobehavioral development. To our knowledge, this is the first study demonstrating neuroprotective effects of recombinant Trx proteins on the outcome of neonatal hypoxia/ischemia, implying clinical potential as neuroprotective agents that might counteract neonatal hypoxia/ischemia injury.

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