A New Approach for Exploring Reperfusion Brain Damage in Hypoxic Ischemic Encephalopathy.

Reperfusion is an essential pathological stage in hypoxic ischemic encephalopathy (HIE). Although the Rice-Vannucci model is widely used in HIE research, it remains difficult to replicate HIE-related reperfusion brain injury. The purpose of this study is to establish a rat model of hypoxia ischemia reperfusion brain damage (HIRBD) using a common carotid artery (CCA) muscle bridge in order to investigate the mechanisms of cerebral resistance to hypoxic-ischemic and reperfusion brain damage. Random assignment of Sprague-Dawley (SD) rats to the Sham, HIRBD, and Rice-Vannucci groups. Changes in body weight, mortality rate, spontaneous alternation behavior test (SAB test), and dynamic changes in cerebral blood flow (CBF) were detected. The damaged cerebral cortices were extracted for morphological comparison, transcriptomic analysis, and quantitative real-time PCR. Harvesting the hippocampus for transmission electron microscopy (TEM) detection. As a result, CCA muscle bridge could effectively block CBF, which recovered after the muscle bridge detachment. Pathological comparison, the SAB test, and TEM analysis revealed that brain damage in Rice-Vannucci was more severe than HIRBD. Gpx1, S100a6, Cldn5, Esr1, and Gfap were highly expressed in both HIRBD and Rice-Vannucci. In conclusion, the CCA muscle bridge-established HIRBD model could be used as an innovative and dependable model to simulate pathological process of HIRBD.

Astaxanthin Ameliorates Ischemic-Hypoxic-Induced Neurotrophin Receptor p75 Upregulation in the Endothelial Cells of Neonatal Mouse Brains.

Ischemic stroke is a leading cause of human death in present times. Two phases of pathological impact occur during an ischemic stroke, namely, ischemia and reperfusion. Both periods include individual characteristic effects on cell injury and apoptosis. Moreover, these conditions can cause severe cell defects and harm the blood-brain barrier (BBB). Also, the BBB components are the major targets in ischemia-reperfusion injury. The BBB owes its enhanced protective roles to capillary endothelial cells, which maintain BBB permeability. One of the nerve growth factor (NGF) receptors initiating cell signaling, once activated, is the p75 neurotrophin receptor (p75NTR). This receptor is involved in both the survival and apoptosis of neurons. Although many studies have attempted to explain the role of p75NTR in neurons, the mechanisms in endothelial cells remain unclear. Endothelial cells are the first cells to encounter p75NTR stimuli. In this study, we found the upregulated p75NTR expression and reductive expression of tight junction proteins after in vivo and in vitro ischemia-reperfusion injury. Moreover, astaxanthin (AXT), an antioxidant drug, was utilized and was found to reduce p75NTR expression and the number of apoptotic cells. This study verified that p75NTR plays a prominent role in endothelial cell death and provides a novel downstream target for AXT.

Mild hypothermia pretreatment attenuates liver L02 cells hypoxic-ischemia reperfusion injury through inhibiting JNK activation / 中华器官移植杂志

Objective To investigate the protective effects and the possible mechanisms of mild hypothermia against liver L02 cells hypoxic-ischernia reperfusion injury by using mild hypothermia pretreatment.Methods L02 cells were randomly divided into three groups:normal control group (N group),hypoxic-ischemia reperfusion group (control group) and hypoxic-ischemia reperfusion with mild hypothermia pretreatment group (experimental group).Before hypoxic-ischemia reperfusion,cells in experimental group were pretreated with mild hypothermia for 6 h,while the other groups were given the normal culture.Thereafter,the hypoxic-ischemia reperfusion models of L02 cells were performed by a tri-gas incubator to hypoxic-ischemia culture for 12 h,followed by reperfusion with normal conditions for 4 hours.Cells in N group were cultured in normal conditions.The temperature of experimental groups was set to 32 C.The samples were collected,and the cell injury,the cell vitality,the cell apoptosis and the expression of JNK in different groups were detected.Results Compared to N group,the levels of alanine aminotransferase (ALT),aspartate transaminase (AST) and lactic dehydrogenase (LDH) were significantly increased,the cell vitality was significantly decreased,the cell apoptosis and the expression of p-JNK were significantly increased in control and experimental groups (P ＜ 0.05).Compared to control group,all these changes were significantly ameliorated in experimental group.The levels of ALT,AST and LDH in control group were (30.0 ± 4.6),(26.3 ± 3.8) and (1129.0 ± 134.3) U/L,and those in the experimental group were (21.0 ± 2.7),(18.7 ± 2.1)and (898.3 ± 79.2),respectively.The cell vitality in control group and experimental group was (64.33 ± 2.32)％ and (78.17± 3.01)％ respectively.The cell apoptosis in control group and experimental group was (32.4 ± 2.3) ％ and (18.8 ± 1.4) ％ respectively.The expression of p-JNK in experimental group was significantly decreased.All these differences were statistically significant (P＜0.05).Conclusion Mild hypothermia pretreatment could significantly attenuate liver L02 cells hypoxicischemia reperfusion injury probably by inhibiting JNK activation.

Mild hypothermia pretreatment attenuates liver L02 cells hypoxic-ischemia reperfusion injury through inhibiting JNK activation / 中华器官移植杂志

Objective To investigate the protective effects and the possible mechanisms of mild hypothermia against liver L02 cells hypoxic-ischernia reperfusion injury by using mild hypothermia pretreatment.Methods L02 cells were randomly divided into three groups:normal control group (N group),hypoxic-ischemia reperfusion group (control group) and hypoxic-ischemia reperfusion with mild hypothermia pretreatment group (experimental group).Before hypoxic-ischemia reperfusion,cells in experimental group were pretreated with mild hypothermia for 6 h,while the other groups were given the normal culture.Thereafter,the hypoxic-ischemia reperfusion models of L02 cells were performed by a tri-gas incubator to hypoxic-ischemia culture for 12 h,followed by reperfusion with normal conditions for 4 hours.Cells in N group were cultured in normal conditions.The temperature of experimental groups was set to 32 C.The samples were collected,and the cell injury,the cell vitality,the cell apoptosis and the expression of JNK in different groups were detected.Results Compared to N group,the levels of alanine aminotransferase (ALT),aspartate transaminase (AST) and lactic dehydrogenase (LDH) were significantly increased,the cell vitality was significantly decreased,the cell apoptosis and the expression of p-JNK were significantly increased in control and experimental groups (P ＜ 0.05).Compared to control group,all these changes were significantly ameliorated in experimental group.The levels of ALT,AST and LDH in control group were (30.0 ± 4.6),(26.3 ± 3.8) and (1129.0 ± 134.3) U/L,and those in the experimental group were (21.0 ± 2.7),(18.7 ± 2.1)and (898.3 ± 79.2),respectively.The cell vitality in control group and experimental group was (64.33 ± 2.32)％ and (78.17± 3.01)％ respectively.The cell apoptosis in control group and experimental group was (32.4 ± 2.3) ％ and (18.8 ± 1.4) ％ respectively.The expression of p-JNK in experimental group was significantly decreased.All these differences were statistically significant (P＜0.05).Conclusion Mild hypothermia pretreatment could significantly attenuate liver L02 cells hypoxicischemia reperfusion injury probably by inhibiting JNK activation.

Change of Nuclear Factor-?B Signaling Pathway Alteration in Neonatal Rats with Early Hypoxic-Ischemic Reperfusion Brain Damage / 实用儿科临床杂志

Objective To explore the changes of genes associated with the nuclear factor of kappa B(NF-?B) signaling pathway in neonatal rats with early hypoxic-ischemic reperfusion brain damage(HIRBD).Methods Twenty-four SD rats at age of 7 days,with male to female of 1212,were randomized into normal control group(group A,n=8),hypoxic-ischemia reperfusion for 2 h(group B,n=8) and hypoxic-ischemia reperfusion for 4 h(group C,n=8).The tissues of hippocampus were taken for complete RNA extraction.Gene chip inspection and biological signal analysis technique were used to detect the expression of 113 involved signal molecules of NF-?B pathway.Results Compared with group A,the up-regulated expression was found in Chemokine(C-C motif) ligand 2,Dual specificity phosphatase 1,FBJ osteosarcoma oncogene(Fos) and Toll-like receptor 9.Whereas the expressions of Caspase-1,8,Mitogen-activated protein kinase kinase 6,Mitogen activated protein kinase 3 and Ras homolog gene family member a from Ras-gene famimly was found down-regulated in group B.The up-regulated expression was in Fos,IL-1? and Toll-like receptor 6,but that of down-regulation was found in Caspase-1,Extracellular matrix protein 1,Lysophosphatidic Acid G-protein-coupled receptor 2,Mucosa associated lymphoid tissue lymphoma translocation gene 1,Inhibitor of kappa B kinase epsilon and Ras homolog gene family member c.Conclusions At the early stage of HIRBD,the Toll-like receptors may induce NF-?B activation,leading to the coordinated induction of multiple genes,which is involved in inflammatory,apoptosis and cell proliferation.Genes induced by NF-?B are responsible for the physiopathological process of early brain damage in neonatal rats with HIRBD.

Effect of Exogenous Adrenomedullin on the Glutathion Levels of Plasma and Brain Tissue in Neonatal Rat with Hypoxic-Ischemia Reperfusion Brain Damage / 实用儿科临床杂志

Objective To explore the effect of exogenous adrenomedullin(ADM) on expressions of glutathion in plasma and brain tissue inneonatal rats with hypoxic-ischemia reperfusion brain damage(HIRBD) and the mechanism of action.Methods Fifty-six cases of 7 d SD rats were randomly divided into 4 groups including normal control group(without any treatment),HIRBD group(the model with hypoxia for 2 h and ischemia for 1 h),primed group(abdomen infusion of ADM at 0.5 h before making model,the other was same to the HIRBD group)and treatment group(abdomen infusion of ADM at onces after making model,the other was same to the HIRBD group).The neonatal rats in 4 groups were derived blood and brain tissue after decapitation at either 4 h or 24 h after reperfusion.The levels of gtutathion(GSH) in plasma and brain tissue were determined by using chromatometry.Results In HIRBD group,the affection areas at 24 h after reperfusion enlarged compared with those at 4 h after reperfusion.Meanwhile,the affection of punctiform degeneration or necrosis at 4 h after reperfusion transformed into the affection of lamellar or diffuse degeneration or necrosis at 24 h after reperfusion.The levels of GSH in plasma and brain tissue in HIRBD group at either 4 h or 24 h after reperfusion were significantly lower than that in normal control group(Pa0.05).Meanwhile the pathology score of brain section in primed group and treatment group were significantly lower than that in HIRBD group at either 4 h or 24 h after reperfusion(Pa0.05).Conclusion Exogenous ADM can induce the neuroprotection in HIRBD by adjusting the expression of GSH.