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.

Tanshinone IIa Alleviates the Biochemical Changes Associated with Hypoxic Ischemic Brain Damage in a Rat Model

2011 ◽  
Vol 25 (12) ◽  
pp. 1865-1869 ◽  
Author(s):  
Mingyan Hei ◽  
Yali Luo ◽  
Xiaochun Zhang ◽  
Furong Liu
Keyword(s):  
Brain Damage ◽  
Rat Model ◽  
Biochemical Changes ◽  
Tanshinone Iia ◽  
Ischemic Brain Damage ◽  
Ischemic Brain

scholarly journals Effects of MicroRNA-592-5p on Hippocampal Neuron Injury Following Hypoxic-Ischemic Brain Damage in Neonatal Mice - Involvement of PGD2/DP and PTGDR

2018 ◽  
Vol 45 (2) ◽  
pp. 458-473 ◽  
Author(s):  
Li-Qun Sun ◽  
Gong-Liang Guo ◽  
Sai Zhang ◽  
Li-Li  Yang
Keyword(s):  
Cell Cycle ◽  
Mouse Model ◽  
Signaling Pathway ◽  
Brain Damage ◽  
Target Gene ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Expression Levels ◽  
Neonatal Mice ◽  
Group A

Background/Aims: This study aimed to explore the effect of microRNA-592-5p (miR-592-5p) on hypoxic-ischemic brain damage (HIBD)-induced hippocampal neuronal injury in a neonatal mouse model relative to the involvement of one target gene, PTGDR, and the PGD2/ DP signaling pathway. Methods: A total of 30 neonatal mice aged 7 days were randomly selected to establish an HIBD mouse model. Hippocampal neuronal cells were transfected into a control group, a blank group, a negative control (NC) group, an miR-592-5p mimics group, an miR-592-5p inhibitors group, an siRNA-PTGDR group and an miR-592-5p inhibitors + siRNA-PTGDR group. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analyses were performed to detect the expression levels of miR-592-5p, PTGDR, DP2, Bcl-2 and Bax in tissues and cells. Cell proliferation, cell cycle and apoptosis were detected by MTT assay and flow cytometry, respectively. Results: The expression levels of miR-592-5p and Bcl-2 decreased, while the expression levels of PTGDR, DP2 and Bax increased in the HIBD group. PTGDR is a target gene of miR-592-2p. Compared with the NC and blank groups, the expression levels of PTGDR, DP2 and Bax decreased, while the expression levels of miR-592-5p and Bcl-2 increased in the miR-592-5p mimics group. The siRNA-PTGDR group showed the same trend as that observed in the miR-592-5p mimics group, except with no difference in miR-592-5p expression. The miR-592-5p inhibitors group showed an opposite gene expression trend compared to that in the miR-592-5p mimics group. The S phase of the cell cycle was prolonged, the G1 phase was reduced, proliferation was increased, and the apoptosis rate was decreased in the siRNA-PTGDR and miR-592-5p mimics groups. Opposite trends for cell cycle, proliferation and apoptosis were observed in the miR-592-5p inhibitors group. Conclusions: Our study suggests that miR-592-5p upregulation protects against hippocampal neuronal injury caused by HIBD by targeting PTGDR and inhibiting the PGD2/DP signaling pathway.

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 Bilateral Molecular Changes in a Neonatal Rat Model of Unilateral Hypoxic-Ischemic Brain Damage

2006 ◽  
Vol 59 (3) ◽  
pp. 434-439 ◽  
Author(s):  
Evelyn R W van den Tweel ◽  
Annemieke Kavelaars ◽  
Maria Stella Lombardi ◽  
Cora H A Nijboer ◽  
Floris Groenendaal ◽  
...  
Keyword(s):  
Brain Damage ◽  
Rat Model ◽  
Neonatal Rat ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Molecular Changes ◽  
Neonatal Rat Model

A Rat Model for Hypoxic-Ischemic Brain Damage in Very Premature Infants

Neonatology ◽  
1996 ◽  
Vol 69 (5) ◽  
pp. 327-341 ◽  
Author(s):  
Ann Sheldon ◽  
Jing Chuai ◽  
Donna M. Ferriero
Keyword(s):  
Brain Damage ◽  
Premature Infants ◽  
Rat Model ◽  
Ischemic Brain Damage ◽  
Ischemic Brain ◽  
Very Premature Infants
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