scholarly journals Failure of Iron Chelators to Protect Against Cerebral Infarction in Hypoxia-Ischemia

1993 ◽  
Vol 20 (1) ◽  
pp. 41-43 ◽  
Author(s):  
V. MacMillan ◽  
I. Fridovich ◽  
J. Davis
Keyword(s):  
Carbon Monoxide ◽  
Cerebral Infarction ◽  
Brain Damage ◽  
Histological Examination ◽  
Iron Chelators ◽  
Ischemic Brain ◽  
Hypoxia Ischemia ◽  
The Mean ◽  
Preliminary Study ◽  
The Brain

ABSTRACT:In this study the ability of iron chelators to attenuate hypoxic-ischemic brain damage was assessed in hyperglycemic rats that were exposed to 1% carbon monoxide and right carotid occlusion. The animals received deferoxamine (50 mg/kg), manganese-deferoxamine (50 mg/kg) or vehicle i.p. 0.5 h prior to hypoxemic-ischemic exposure and at 0.5, 3 and 24 h post-exposure; with subsequent histological examination of the brain at 7 days recovery. The area of cerebral infarction was measured at three levels using video imaging methods. The mean percentage of total hemisphere that was infarcted in the three groups was: vehicle — 28.5 ± 5.0; deferoxamine — 31.7 ± 12.1; and manganese deferoxamine — 30.6 ± 6.8 (p - n.s.). The results as obtained in this preliminary study indicate that aggressive pre- and post-treatment with iron chelators has no ability to attenuate cerebral infarction in this model.

scholarly journals Hydrogen inhalation protects hypoxic–ischemic brain damage by attenuating inflammation and apoptosis in neonatal rats

2019 ◽  
Vol 244 (12) ◽  
pp. 1017-1027 ◽  
Author(s):  
Guojiao Wu ◽  
Zhiheng Chen ◽  
Peipei Wang ◽  
Mingyi Zhao ◽  
Masayuki Fujino ◽  
...  
Keyword(s):  
Brain Injury ◽  
Inflammatory Response ◽  
Spatial Memory ◽  
Brain Damage ◽  
Morris Water Maze Test ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Hypoxia Ischemia ◽  
The Brain

Hypoxic–ischemic brain damage (HIBD) is one of the leading causes of brain injury in infant with high risk of mortality and disability; therefore, it is important to explore more feasible and effective treatment strategies. Here, we assessed the neuroprotective effects of different hydrogen inhalation times for the treatment of HIBD. We induced hypoxia–ischemia in Sprague–Dawley rats (postnatal day 7, both sexes), followed by treatment with hydrogen inhalation for 30, 60, or 90 min. Morphological brain injury was assessed by Nissl and TUNEL staining. Acute inflammation was evaluated by examining the expression of interleukin-1β (IL-1β) and NF-κB p65, as well as Iba-1 immunofluorescence in the brain. Neural apoptosis was evaluated by examining the expression of P-JNK and p53 as well as NeuN immunofluorescence. Neurobehavioral function of rats was evaluated by Morris water maze test at 36 days after surgery. The results showed that hypoxia–ischemia injury induced the inflammatory response of microglia; however, these changes were inhibited by hydrogen inhalation. The inhibitory effects became more apparent as the treatment duration increased ( P < 0.05). Furthermore, hypoxia–ischemia induced neuronal damage and increased the expression of the apoptotic factors, P-JNK, and p53, which were attenuated by hydrogen inhalation ( P < 0.05). Hypoxia–ischemia caused long-term spatial memory deficits during brain maturation, which were ameliorated by hydrogen inhalation ( P < 0.01). In conclusion, hypoxia–ischemia induced severe long-term damage to the brain, which could be alleviated by hydrogen inhalation in a time-dependent manner. Impact statement Oxidative stress is known to be involved in the main pathological progression of neonatal hypoxic–ischemic brain damage (HIBD). Hydrogen (H2) is an antioxidant that can be used to treat HIBD; however, the mechanism by which hydrogen may be used as a promising treatment for neonates with HIBD is not very clear. This study demonstrated that inhaled H2 is neuroprotective against HIBD in SpragueDawley rats by inhibiting the brain’s inflammatory response and neuronal apoptosis or damage and protecting against spatial memory decline. Further, this study showed that inhaled H2 has potential as a therapeutic approach for HIBD. This is relevant to clinical treatment protocols when hypoxia–ischemia is suspected in neonates.

scholarly journals Disruption of the Serotonergic System after Neonatal Hypoxia-Ischemia in a Rodent Model

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kathryn M. Buller ◽  
Julie A. Wixey ◽  
Hanna E. Reinebrant
Keyword(s):  
Clinical Intervention ◽  
Rodent Model ◽  
Neonatal Brain ◽  
Ischemic Brain ◽  
Neonatal Hypoxia ◽  
Brain Injured ◽  
Hypoxia Ischemia ◽  
Stem Damage ◽  
The Brain ◽  
Transporter Expression

Identifying which specific neuronal phenotypes are vulnerable to neonatal hypoxia-ischemia, where in the brain they are damaged, and the mechanisms that produce neuronal losses are critical to determine the anatomical substrates responsible for neurological impairments in hypoxic-ischemic brain-injured neonates. Here we describe our current work investigating how the serotonergic network in the brain is disrupted in a rodent model of preterm hypoxia-ischemia. One week after postnatal day 3 hypoxia-ischemia, losses of serotonergic raphé neurons, reductions in serotonin levels in the brain, and reduced serotonin transporter expression are evident. These changes can be prevented using two anti-inflammatory interventions; the postinsult administration of minocycline or ibuprofen. However, each drug has its own limitations and benefits for use in neonates to stem damage to the serotonergic network after hypoxia-ischemia. By understanding the fundamental mechanisms underpinning hypoxia-ischemia-induced serotonergic damage we will hopefully move closer to developing a successful clinical intervention to treat neonatal brain injury.

Human C-Reactive Protein Enhances Vulnerability of Immature Rats to Hypoxic-Ischemic Brain Damage: A Preliminary Study

2010 ◽  
Vol 17 (5) ◽  
pp. 419-425 ◽  
Author(s):  
Yukiko Kinugasa-Taniguchi ◽  
Takuji Tomimatsu ◽  
Kazuya Mimura ◽  
Takeshi Kanagawa ◽  
Koichiro Shimoya ◽  
...  
Keyword(s):  
Brain Damage ◽  
C Reactive Protein ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Reactive Protein ◽  
Immature Rats ◽  
Preliminary Study

scholarly journals Calcium Accumulation during the Evolution of Hypoxic—Ischemic Brain Damage in the Immature Rat

1988 ◽  
Vol 8 (6) ◽  
pp. 834-842 ◽  
Author(s):  
Dagmar T. Stein ◽  
Robert C. Vannucci
Keyword(s):  
Brain Damage ◽  
Cerebral Hemisphere ◽  
Ischemic Injury ◽  
Calcium Flux ◽  
Variable Degree ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Calcium Accumulation ◽  
Hypoxia Ischemia ◽  
Hypoxic Ischemic Injury

An excessive accumulation of calcium in neuronal and other tissues has been postulated to represent a “final common pathway” for cell death arising from hypoxia-ischemia. To clarify the role of altered calcium flux into and distribution within the perinatal brain undergoing hypoxic-ischemic injury, 7-day postnatal rats underwent unilateral common carotid artery ligation followed by 3 h of hypoxia with 8% oxygen. This insult is known to produce brain damage confined to the cerebral hemisphere ipsilateral to the arterial occlusion in >90% of the animals. Either before or after hypoxia-ischemia, the animals received a subcutaneous injection of [45Ca]Cl2, and their brains were subjected to 45Ca autoradiography at 0–1, 5, 24, and 72 h, 7 or 15 days thereafter. During hypoxia-ischemia, calcium flux into the ipsilateral cerebral hemisphere was prominent in 13 of 14 rat pups, especially in neocortex, hippocampus, striatum, and thalamus. Calcium accumulation also occurred to a variable degree (6 of 14 animals) in the contralateral cerebral hemisphere. During recovery, radioactivity in the contralateral cerebral hemisphere was no longer apparent, whereas in the ipsilateral hemisphere, the extent of calcium accumulation was mild in four of six at 1 h, moderate in three of six at 5 h, moderate to intense in six of seven and six of seven at 24 and 72 h, respectively, and intense in three of three and two of two animals at 7 and 15 days, respectively. As during hypoxia-ischemia, the distribution of the radioactivity was most prominent in those structures that are known to be vulnerable to hypoxic-ischemic injury. Thus, hypoxia-ischemia is associated with enhanced calcium uptake into the immature brain, which does not dissipate but rather progressively accumulates for up to 15 days of recovery. The findings implicate a disruption of intracellular calcium homeostasis as a major factor in the evolution of perinatal hypoxic-ischemic brain damage.

scholarly journals Extracellular Vesicle-Derived microRNA-410 From Mesenchymal Stem Cells Protects Against Neonatal Hypoxia-Ischemia Brain Damage Through an HDAC1-Dependent EGR2/Bcl2 Axis

2021 ◽  
Vol 8 ◽  
Author(s):  
Jun Han ◽  
Si Yang ◽  
Xiaosheng Hao ◽  
Bo Zhang ◽  
Hongbo Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cerebral Infarction ◽  
Brain Damage ◽  
Neuronal Apoptosis ◽  
Edema Formation ◽  
Infarction Volume ◽  
Hypoxia Ischemia

Hypoxia-ischemia brain damage (HIBD) is a neurological disorder occring in neonates, which is exacerbated by neuronal apoptosis. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) have been proposed as a promising strategy for treating or preventing ischemia-related diseases. However, their mechanisms in HIBD remain unclear. Thus, we aimed to address the role of EV-derived microRNA (miR)-410 in HIBD. Neonatal HIBD mouse model was constructed using HI insult, from which neurons were isolated, followed by exposure to oxygen glucose deprivation (OGD). EVs were isolated from human umbilical cord (hUC)-derived MSCs. In silico analyses, dual-luciferase reporter gene and chromatin immunoprecipitation assays were adopted to determine relationships among miR-410, histone deacetylase 1 (HDAC1), early growth response protein 2 (EGR2), and B cell lymphoma/leukemia 2 (Bcl2). The functional roles of EV-derived miR-410 were determined using loss- and gain-of functions experiments, and by evaluating neuronal viability, cell-cycle distribution and neuronal apoptosis in vitro as well as modified neurological severity score (mNSS), edema formation, and cerebral infarction volume in vivo. hUC-MSCs-derived EVs protected against HIBD in vivo and inhibited the OGD-induced neuronal apoptosis in vitro. miR-410 was successfully delivered to neurons by hUC-MSCs-EVs and negatively targeted HDAC1, which inversely mediated the expression of EGR2/Bcl2. Upregulation of EV-derived miR-410 promoted the viability but inhibited apoptosis of neurons, which was reversed by HDAC1 overexpression. EV-derived miR-410 elevation reduced mNSS, edema formation, and cerebral infarction volume by increasing EGR2/Bcl2 expression through downregulating HDAC1 expression in vivo. In summary, EV-derived miR-410 impeded neuronal apoptosis by elevating the expression of EGR2/Bcl2 via HDAC1 downregulation, thereby providing a potential strategy for treating or preventing HIBD.

scholarly journals Characteristics of nervous tissue after modeling of focal cerebral ischemia in rats at different periods of reperfusion

2018 ◽  
Vol 24 (3) ◽  
pp. 58-64
Author(s):  
O.I. Savchuk ◽  
G.G. Skibo
Keyword(s):  
Cerebral Ischemia ◽  
Brain Damage ◽  
Nervous Tissue ◽  
Focal Cerebral Ischemia ◽  
Tactile Sensitivity ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Ischemic Period ◽  
The Brain ◽  
Occlusion Period

The stroke-causing problems are extremely important in Ukraine. This makes a heavy burden not only on the health care system, but also on the whole society as a whole. That's why we've studied structural and ultrastructural changes of cortical neurons and striatum of the brain and the development of delayed death of nerve cells after the modeling of the middle cerebral artery occlusion (MCAO) and post ischemic period in rats. We've analyzed the data at different terms after modeling of MCAO. The purpose of the study was to investigate the changes in the nervous tissue in the modeling of focal cerebral ischemia by monofilament occlusion of MCAO in rats at different periods of reperfusion. The statistical processing of primary digital experimental data was carried out using the software Statistica 6.0. It was confirmed that the 60-minute occlusion of the MCAO is an adequate model of focal ischemic brain damage in rats. Changes of locomotor activity and a tactile sensitivity were determined in rats after occlusion and after reperfusion during the post-period period. It was found that in the experimental group with a reperfusion period of 72 hours, a clear increase of the volume of the ischemic area of the brain, accompanied by significant neurological deficiency, was observed. Reduced research activity of the rats was revealed, which was shown in the decrease of the number of squares they crossed, the number of racks, the increase of acts of grooming and the duration of acts of frizings. Following ischemic brain damage, there was also a disbalance of somato-sensory functions, as evidenced by an increase in the time during which the animal took a test stimulus ("Sticky tape") from both the anterior paws when tested for tactile sensitivity (adhesive removal test). An electron microscopic study of the cortex showed that dark wrinkled neurons and enlightened swollen neurons were observed at 72 hours of post-occlusion period, indicating different ways of death of these cells. Changes in striatum were similar to changes in the cortex, which progressed with an increase in the post-occlusion period. The protocol of the serial evaluation of neurological disorders used after MCAO modeling allowed detecting long-term stable functional disorders in laboratory rats. The obtained data indicate significant changes in the structure of the cortex and striatum in the post-ischemic period and the progressive nature of these changes.

scholarly journals Circulating Tight-Junction Proteins Are Potential Biomarkers for Blood-Brain Barrier Function in a Model of Neonatal Hypoxic/Ischemic Brain Injury

2020 ◽  
Author(s):  
Axel Erik Andersson ◽  
Carina Mallard ◽  
Carl Joakim Ek
Keyword(s):  
Brain Injury ◽  
Blood Brain Barrier ◽  
Brain Injuries ◽  
Brain Barrier ◽  
Neonatal Brain ◽  
Ischemic Brain ◽  
Blood Brain ◽  
Hypoxia Ischemia ◽  
The Brain ◽  
Junction Proteins

Abstract BackgroundNeonatal hypoxia-ischemia often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal brain pathologies but there is a lack of diagnostic tools to evaluate the brain vascular health of neonates in a clinical setting. Measurement of blood-brain barrier tight-junction proteins have shown promise as biomarkers for brain injury in the adult. Here we tested the biomarker potential of tight-junctions in the context of neonatal brain injury.MethodsThe levels of TJ-proteins (occluding, claudin-5, and zonula occludens-1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood-brain barrier function were measured in a clinically relevant hypoxia/ischemia model in neonatal rats.ResultsTemporally acute elevated levels of occludin and claudin-5 could be measured in blood and CSF after hypoxia/ischemia with males generally having higher levels than females. The levels of claudin-5 in CSF correlated with the severity of the brain injury at 24h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood-brain barrier-permeability at 6 and 24h after hypoxia/ischemia.ConclusionsLevels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood-brain barrier-impairment and have promise as early biomarkers for cerebral vascular health and as a tool for risk assessment of neonatal brain injuries.

Significant Role of microRNA-182-5p in Neonatal Hypoxic-Ischemic Injury and Related Mechanism

2020 ◽  
Vol 10 (5) ◽  
pp. 654-661
Author(s):  
Qin Wang ◽  
Ting Wang
Keyword(s):  
Cell Viability ◽  
Brain Tissue ◽  
Brain Damage ◽  
Rat Model ◽  
Target Gene ◽  
Luciferase Reporter ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Qrt Pcr ◽  
The Brain

The purpose of current study was to explore the role and mechanism of microRNA-182-5p (miR182-5p) in neonatal hypoxic ischemic brain damage (HIBD). First, we established a hypoxic-ischemic (HI) rat model and assessed the neurological function of the rats using the Zea Longa score. Then, the level of miR-182-5p in brain tissue of neonatal rats was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Findings revealed that miR-182-5p was significantly down-regulated in the brain tissue of HI rat model. Next, we studied the target gene of miR-182-5p by using TargetScan and dual luciferase reporter assay. Results showed that CASP2 was a direct target gene of miR-182-5p, and the level of CASP2 was significantly up-regulated in the brain tissue of HI rat model. Immediately thereafter, we established an oxygen and glucose deprivation (OGD) cell model of primary cortical neurons, and demonstrated the changes of miR182-5p in cells treated with OGD by qRT-PCR. Finally, to determine the function of miR-182-5p in OGD subjected neuronal cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry (FCM) assays were used to study cell viability and apoptosis. The study found that compared with the OGD group, miR-182-5p mimic significantly increased nerve cell viability, reduced cell apoptosis and decreased cleaved-Caspase3/7/8 protein expression, however, all these changes were significantly reversed by overexpression of the CASP2 gene. Taken together, miR-182-5p might protect the nerve cells from ischemia and hypoxia by targeting CASP2, thereby playing a protective role in hypoxic ischemic encephalopathy, which might be a new effective target for neonatal hypoxic ischemic brain damage treatment.

scholarly journals Serum 24S-hydroxycholesterol predicts long-term brain structural and functional outcomes after hypoxia-ischemia in neonatal mice

2020 ◽  
pp. 0271678X2091191 ◽  
Author(s):  
Fuxin Lu ◽  
Shujuan Fan ◽  
Andrea R Romo ◽  
Duan Xu ◽  
Donna M Ferriero ◽  
...  
Keyword(s):  
Brain Damage ◽  
Functional Outcomes ◽  
Cholesterol Metabolism ◽  
Blue Staining ◽  
Functional Impairments ◽  
Major Pathway ◽  
Hypoxia Ischemia ◽  
Severe Motor ◽  
The Brain

The major pathway of brain cholesterol turnover relies on its hydroxylation into 24S-hydroxycholesterol (24S-HC) using brain-specific cytochrome P450 46A1 (CYP46A1). 24S-HC produced exclusively in the brain normally traverses the blood-brain barrier to enter the circulation to the liver for excretion; therefore, the serum 24S-HC level is an indication of cholesterol metabolism in the brain. We recently reported an upregulation of CYP46A1 following hypoxia-ischemia (HI) in the neonatal mouse brain and a correlation between serum 24S-HC levels and acute brain damage. Here, we performed a longitudinal study to investigate whether the serum 24S-HC concentrations predict long-term brain structural and functional outcomes. In postnatal day 9 mice subjected to HI, the serum 24S-HC levels increased at 6 h and 24 h after HI and correlated with the infarct volumes measured histologically or by T2-weighted MRI. The 24 h levels were associated with white matter volume loss quantified by MBP immunostaining and luxol fast blue staining. The animals with higher serum 24S-HC at 6 h and 24 h corresponded to those with more severe motor and cognitive deficits at 35-40 days after HI. These data suggest that 24S-HC could be a novel and early blood biomarker for severity of neonatal HI brain damage and associated functional impairments.

Measuring the Accentuation of the Brain Damage That Arises from Perinatal Cerebral Hypoxia-Ischemia

Neonatology ◽  
1997 ◽  
Vol 72 (3) ◽  
pp. 187-191 ◽  
Author(s):  
Robert C. Vannucci ◽  
Anthony Rossini ◽  
Javad Towfighi ◽  
Susan J. Vannucci
Keyword(s):  
Brain Damage ◽  
Cerebral Hypoxia ◽  
Hypoxia Ischemia ◽  
The Brain
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