Exogenous β-Hydroxybutyrate Treatment and Neuroprotection in a Suckling Rat Model of Hypoxic-Ischemic Encephalopathy

2018 ◽  
Vol 40 (1) ◽  
pp. 73-83 ◽  
Author(s):  
Byong Sop Lee ◽  
Dong-Cheol Woo ◽  
Chul-Woong Woo ◽  
Ki-Soo Kim
Keyword(s):  
Rat Model ◽  
Hypoxic Ischemic Encephalopathy ◽  
Functional Tests ◽  
Rotarod Test ◽  
Object Recognition Test ◽  
Human Infants ◽  
Rat Pups ◽  
Cylinder Test ◽  
Neuroprotective Efficacy ◽  
Ischemic Encephalopathy

β-Hydroxybutyrate (BHB) is a representative ketone body that may play a role in the mitigation of neonatal hypoxic-ischemic encephalopathy by altering energy metabolism. This study aimed to investigate the neuroprotective efficacy of exogenous BHB administration in a suckling rat model after hypoxia-ischemia (HI). Thirteen-day-old (P13) rat pups were subjected to 120 min of hypoxia according to the Rice-Vannucci model. BHB (5.0 mmol/kg, HI-BHB) or vehicle (0.9% saline, HI-Veh) was administered 0, 2, 4, and 6 h after HI induction. Pathologic injury scores and the number of TUNEL-positive cells were evaluated on P15. Residual hemispheric volume was measured with T2-weighted MRI (on P27) and functional tests, such as the negative geotaxis test, rope suspension test, rotarod test, novel object recognition test, and cylinder test, were performed. Systemic ketosis (approx. 2.0–3.0 mM/L) was well tolerated by the rat pups with no difference in the mortality rate between both groups. Compared with the HI-Veh group, the HI-BHB group demonstrated significantly lower pathological scores as well as fewer TUNEL-positive cells. The intact residual hemispheric and hippocampal volumes were greater in the HI-BHB group than the HI-Veh group. However, the results of functional tests did not differ between both groups. Postischemic BHB administration reduced brain injury in suckling rats after HI. The safe clinical application of our animal model to human infants with HI requires further investigation.

scholarly journals hUC-MSCs Exert a Neuroprotective Effect via Anti-apoptotic Mechanisms in a Neonatal HIE Rat Model

2019 ◽  
Vol 28 (12) ◽  
pp. 1552-1559 ◽  
Author(s):  
Jianwei Xu ◽  
Zhanhui Feng ◽  
Xianyao Wang ◽  
Ying Xiong ◽  
Lan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Rat Model ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Hypoxic Ischemic Encephalopathy ◽  
Human Umbilical Cord ◽  
Motor Functions ◽  
Ischemic Encephalopathy

In this study, we investigated how human umbilical cord mesenchymal stem cells exerted a neuroprotective effect via antiapoptotic mechanisms in a neonatal hypoxic-ischemic encephalopathy rat model. A total of 78 10-day old (P10) rats were used. After human umbilical cord mesenchymal stem cells were collected from human umbilical cords and amplified in culture, they were administered to rat subjects 1 h after induced hypoxic-ischemic encephalopathy treatment. The short-term (48 h) and long-term (28 day) outcomes were evaluated after human umbilical cord mesenchymal stem cells treatment using neurobehavioral function assessment. Triphenyltetrazolium chloride monohydrate staining was performed at 48 h. Beclin-2 and caspase-3 levels were evaluated with Western blot and real time polymerase chain reaction at 48 h. Human umbilical cord mesenchymal stem cells were collected and administrated to hypoxic-ischemic encephalopathy pups by intracerebroventricular injection. Hypoxic-ischemic encephalopathy typically induced significant delay in development and caused impairment in both cognitive and motor functions in rat subjects. Human umbilical cord mesenchymal stem cells were shown to ameliorate hypoxic-ischemic encephalopathy-induced damage and improve both cognitive and motor functions. Although hypoxic-ischemic encephalopathy induced significant expression of caspase-3 and Beclin-2, human umbilical cord mesenchymal stem cells decreased the expression of both of them. Human umbilical cord mesenchymal stem cells may serve as a potential treatment to ameliorate brain injury in hypoxic-ischemic encephalopathy patients.

scholarly journals Exploring Perinatal Asphyxia by Metabolomics

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 141 ◽  
Author(s):  
Emanuela Locci ◽  
Giovanni Bazzano ◽  
Roberto Demontis ◽  
Alberto Chighine ◽  
Vassilios Fanos ◽  
...  
Keyword(s):  
Perinatal Asphyxia ◽  
Relevant Literature ◽  
Hypoxic Ischemic Encephalopathy ◽  
Health Concern ◽  
Resonance Spectroscopy ◽  
Industrialized Countries ◽  
Human Infants ◽  
Therapeutic Tools ◽  
Effective Use ◽  
Ischemic Encephalopathy

Brain damage related to perinatal asphyxia is the second cause of neuro-disability worldwide. Its incidence was estimated in 2010 as 8.5 cases per 1000 live births worldwide, with no further recent improvement even in more industrialized countries. If so, hypoxic-ischemic encephalopathy is still an issue of global health concern. It is thought that a consistent number of cases may be avoided, and its sequelae may be preventable by a prompt and efficient physical and therapeutic treatment. The lack of early, reliable, and specific biomarkers has up to now hampered a more effective use of hypothermia, which represents the only validated therapy for this condition. The urge to unravel the biological modifications underlying perinatal asphyxia and hypoxic-ischemic encephalopathy needs new diagnostic and therapeutic tools. Metabolomics for its own features is a powerful approach that may help for the identification of specific metabolic profiles related to the pathological mechanism and foreseeable outcome. The metabolomic profiles of animal and human infants exposed to perinatal asphyxia or developing hypoxic-ischemic encephalopathy have so far been investigated by means of 1H nuclear magnetic resonance spectroscopy and mass spectrometry coupled with gas or liquid chromatography, leading to the identification of promising metabolomic signatures. In this work, an extensive review of the relevant literature was performed.

scholarly journals FASUDIL HYDROCHLORIDE EFFECTS ON EAAT2 AND ROCK2 PROTEIN EXPRESSIONS IN RAT MODEL OF NEONATAL HYPOXIC-ISCHEMIC ENCEPHALOPATHY.

2017 ◽  
Vol 5 (4) ◽  
pp. 1674-1679
Author(s):  
NdefiA ntimaYadiswaRobert ◽  
◽  
WangXian He ◽  
ZhangYa Li ◽  
ZhuZhang Long ◽  
...  
Keyword(s):  
Rat Model ◽  
Hypoxic Ischemic Encephalopathy ◽  
Protein Expressions ◽  
Ischemic Encephalopathy

scholarly journals Effects of Melatonin and Pentoxyphilline Treatment on Newborn Rat Model of Hypoxic Ischemic Encephalopathy

2011 ◽  
Vol 70 ◽  
pp. 220-220
Author(s):  
O Soz ◽  
M K Turkmen ◽  
A Kumral ◽  
B Baykara ◽  
D C Yesilirmak ◽  
...  
Keyword(s):  
Rat Model ◽  
Hypoxic Ischemic Encephalopathy ◽  
Newborn Rat ◽  
Ischemic Encephalopathy

Transplantation of multipotent astrocytic stem cells into a rat model of neonatal hypoxic–ischemic encephalopathy

2006 ◽  
Vol 1112 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Tong Zheng ◽  
Candace Rossignol ◽  
Avital Leibovici ◽  
Kevin J. Anderson ◽  
Dennis A. Steindler ◽  
...  
Keyword(s):  
Stem Cells ◽  
Rat Model ◽  
Hypoxic Ischemic Encephalopathy ◽  
Ischemic Encephalopathy

scholarly journals Sestrin2, as a negative feedback regulator of mTOR, provides neuroprotection by activation AMPK phosphorylation in neonatal hypoxic-ischemic encephalopathy in rat pups

2016 ◽  
Vol 37 (4) ◽  
pp. 1447-1460 ◽  
Author(s):  
Xudan Shi ◽  
Liang Xu ◽  
Desislava Met Doycheva ◽  
Jiping Tang ◽  
Min Yan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mammalian Target Of Rapamycin ◽  
Adenosine Monophosphate ◽  
Neurological Function ◽  
Hypoxic Ischemic Encephalopathy ◽  
Brain Infarct ◽  
Rat Pups ◽  
Infarct Area ◽  
Ischemic Encephalopathy ◽  
Feedback Regulator

Hypoxic-ischemic encephalopathy is a condition caused by reduced oxygen and cerebral blood flow to the brain resulting in neurological impairments. Effective therapeutic treatments to ameliorate these disabilities are still lacking. We sought to investigate the role of sestrin2, a highly conserved stress-inducible protein, in a neonatal rat hypoxic-ischemic encephalopathy model. Ten-day-old rat pups underwent right common carotid artery ligation followed by 2.5 h hypoxia. At 1 h post hypoxic-ischemic encephalopathy, rats were intranasally administered with recombinant human sestrin2 and sacrificed for brain infarct area measurement, Fluoro-Jade C, immunofluorescence staining, Western blot, and neurological function testing. rh-sestrin2 reduced brain infarct area, brain atrophy, apoptosis, ventricular area enlargement, and improved neurological function. Western blot showed that sestrin2 expression levels were increased after treatment with rh-sestrin2, and sestrin2 exerts neuroprotective effects via activation of the adenosine monophosphate-activated protein kinase pathway which in turn inhibits mammalian target of rapamycin signaling resulting in the attenuation of apoptosis. In conclusions: Sestrin2 plays an important neuroprotective role after hypoxic-ischemic encephalopathy via adenosine monophosphate-activated protein kinase signaling pathway and serves as a negative feedback regulator of mammalian target of rapamycin. Administration of rh-sestrin2 not only reduced infarct area and brain atrophy, but also significantly improved neurological function.

Bacteriophage carriers localize in the brain of a rat model of neonatal hypoxic‐ischemic encephalopathy

2021 ◽  
pp. 2100226
Author(s):  
Abdullah K. Alshememry ◽  
Jung‐Lynn Jonathan Yang ◽  
Edward A. Armstrong ◽  
Jerome Y. Yager ◽  
Larry D. Unsworth
Keyword(s):  
Rat Model ◽  
Hypoxic Ischemic Encephalopathy ◽  
The Brain ◽  
Ischemic Encephalopathy
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