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Protective Effect of Caspase Inhibitor on Neonatal Rat with Hypoxia-Ischemia Brain Damage

Jiahao Liu

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Abstract

Objective To observe the protection of Caspase inhibitor(zVAD-fmk,benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on neonatal rat with hypoxic-ischemic brain damage(HIBD).Methods Thirty-six neonatal rats,7 days old,were randomly divided into hypoxic-ischemic(HI) control group(A),zVAD-fmk treated group(B) and sham group(C).Before HI insult,a pan-Caspase inhibitor,zVAD-fmk or normal buffer solution was injected into the cerebral ventricle.The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer(Annexin V/PI) at 24 hours after HI insult.The effect on body weights(percentage of increased weight,WIP) and macroscopical changes(percentage of cortox and hippocampal dead neurons) were assessed at 14 days.Results Compared with group A,the water content of ischemic hemisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly.The difference of percentage of increased weight at 14 days in group B was not significantly.Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A.Conclusion Intracerebral administration of zVAD-fmk has protective effects on hypoxic-ischemic brain damage in neonatal rat.

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Objective To observe the protection of Caspase inhibitor(zVAD-fmk,benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on neonatal rat with hypoxic-ischemic brain damage(HIBD).Methods Thirty-six neonatal rats,7 days old,were randomly divided into hypoxic-ischemic(HI) control group(A),zVAD-fmk treated group(B) and sham group(C).Before HI insult,a pan-Caspase inhibitor,zVAD-fmk or normal buffer solution was injected into the cerebral ventricle.The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer(Annexin V/PI) at 24 hours after HI insult.The effect on body weights(percentage of increased weight,WIP) and macroscopical changes(percentage of cortox and hippocampal dead neurons) were assessed at 14 days.Results Compared with group A,the water content of ischemic hemisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly.The difference of percentage of increased weight at 14 days in group B was not significantly.Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A.Conclusion Intracerebral administration of zVAD-fmk has protective effects on hypoxic-ischemic brain damage in neonatal rat.

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Available abstract

Objective To observe the protection of Caspase inhibitor(zVAD-fmk,benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone) on neonatal rat with hypoxic-ischemic brain damage(HIBD).Methods Thirty-six neonatal rats,7 days old,were randomly divided into hypoxic-ischemic(HI) control group(A),zVAD-fmk treated group(B) and sham group(C).Before HI insult,a pan-Caspase inhibitor,zVAD-fmk or normal buffer solution was injected into the cerebral ventricle.The water content of cerebral hemisphere was measured and the percentage of apoptofic cells in hippocampal neurons was measured by Flow cytometer(Annexin V/PI) at 24 hours after HI insult.The effect on body weights(percentage of increased weight,WIP) and macroscopical changes(percentage of cortox and hippocampal dead neurons) were assessed at 14 days.Results Compared with group A,the water content of ischemic hemisphere and apoptosis percentage of hippocampal neurons in group B reduced significantly.The difference of percentage of increased weight at 14 days in group B was not significantly.Microscopic examination showed that cortox and hippocampus neural death rate in group B was proved significantly reduced compared with that in group A.Conclusion Intracerebral administration of zVAD-fmk has protective effects on hypoxic-ischemic brain damage in neonatal rat.

Key concepts: Hippocampal formation, Brain damage, Hippocampus, Ventricle, Neuroprotection, Anesthesia, Hypoxia (environmental), Apoptosis

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