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The Study On Protective Effect And Its Mechanism Of Hyperbaric Oxygen On Hypoxic-Ischemic Brain Damage On The Neonatal Rat

Posted on:2004-11-25Degree:DoctorType:Dissertation
Country:ChinaCandidate:L LiuFull Text:PDF
GTID:1104360092487061Subject:Academy of Pediatrics
Abstract/Summary:PDF Full Text Request
I . Research backgroundNeonatal hypoxic-ischemic encephalopathy (HIE) is a common disease of the central nervous system of newborn infants during perinatal period. The mortality of the disease is high and the prognosis of it is very poor. It is one of the main causes of invalidity in children. The research on its pathogenesis and therapy is the hot pot of neonatal specialty. According to the reports of literature, the pathogenesis of the disease is related to acidosis, toxicity of excitatory arnino acids such as glutamate, oxygen-derived free radicals, calcium overload and injury of cell phospholipid etc that are the results of energy failure of brain hypoxic-ischemia. Research shows: the hypoxic-ischemic brain damage includes necrosis and apoptosis of nerve cells. Necrosis happens earlier and quicker than apoptosis. After one hour of hypoxic-ischemia of brain, necrosis can be seen which is often located in the central part of the lesion, develops very quickly and lasts for five days. But apoptosis is frequently located in the peripheral part of the lesion. They can be seen after two hours of brain hypoxic-ischemia, reaches peak levels in two days and will last for twenty one days. Necrosis nearly stops or reduces after four or five days of brain hypoxic-ischemia, but apoptosis still continues. It is thus evident that apoptosis has a key role in the development of late brain injury. The apoptosis of nerve cell will enlarge the lesion of brain damage. If the progress of apoptosis is stopped, the degree of HIBD will be relieved.Hyperbaric oxygenation (HBO) is the breathing of pure oxygen in a high pressure environment. As a special treatment, HBO has been used in clinic work extensively at home and abroad. Clinical practice shows that HBO has significant effect on some disease such as CO poisoning, some infections caused by anaerobes, diving decompression sickness, tissue hypoxic-ischemia, craniocerebral injury, spinal cord injury etc. But there is different opinion about HBO's use on HIBD of neonates. Some scholars think HBO can raise the oxygen pressure of blood, improve the supply of oxygen, metabolism and microcirculation of brain, reduce the brain edema, stop the pathway of free radical production, reinforce the enzyme synthesis in mitochondrion, accelerate the recovery of brain injury, decrease the infarct and apoptosis of brain tissues. Other researchers have opposing ideas and believe that HBO can increase the production of oxygen free radical, have the poison effect for nerve cells, accelerate thedeath of nerve cells and make the HIBD become severe. The reasons of the different opinions may relate to different conditions of different experiment. In addition, the reports of HBO are more about application researches before. There are fewer researches which inquires on the therapeutic mechanism of HBO on the molecular level especially the important question that is whether HBO can relieve the apoptosis of nerve cells has not been reported. It is difficult to make a conclusion at this point on whether HBO has the therapeutic effect on HIE and further research needs be done.NF- K B is a kind of nuclear transcription factor which is related to some important processes of inflammation, immune reaction, oxidative stress and many pathophysical process of body . It has an important role in the development of diseases. The inactivated NF- K. B exists in cytoplasm as a combination of P50, P65 and inhibiting protein of I kBa. When NF- K B accepts the signal stimulation from the outside of cells, I K B a will be phosphorated and then separated from NF- K B trimmers. This activated NF- K B will regulate some gene transcription. Some literature reported the suitable activating of NF- K B can improve the expression of anti-apoptosis genes such as Bcl-2, Bcl-X, c-IAP and Mn-SOD, block the biochemical cascade of early apoptosis, inhibit the release of cytochrome C caused by hypoxia, keep the integrity of mitochondria membrane, inhibit overloading of Ca2+ in intracellular and finally relieve the development proce...
Keywords/Search Tags:hyperbaric oxygen, hypoxic ischemic brain damage, apoptosis of nerve cell, Bcl-2, Bax, NF-кB, cytochrome C, SOD, MDA
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