| The hypoxic-ischemic brain damage induced by perinatal suffocation is one of thefrequent and severe disease, often cause nervous system developmental disability andneonatal death. With the rapid development of perinatal medicine, the prevention and controlof the neonatal hypoxic-ischemic brain injury has become an important topic fof the medicalresearch.The main pathological changes of neonatal hypoxic-ischemic encephalopathy (NHIE)are the loss of cells and contacts among the cells. There are numerous factors involved in thetreatment of hypoxic-ischemic brain injury. One of them is the application of glucocorticoids(GC). Clinical application of glucocorticoids for the treatment of NHIE is against brain edemaand inflammation. But there was debate on the usage of glucocorticoids in the treatment ofhypoxic-ischemic brain injury on the newborn for the inevitable and severe side effects.The glucocorticoids could regulat the development of dendritic spines and the synapticplasticity. What did electrophysiological characteristics changes happen immediately after theinjury? How did dendritic trees of rat hippocampal pyramidal cells develop in NHIE? Whatfunction did corticosteroids perform during the course of treatment? All of these were stilllack related studies.This study used the rat NHIE animal model(estabilished at postnatal7days through leftcommon carotid artery interception and then exposed to8%oxygen at37°C for90min),through the application of patch clamp technique to reveal the electrophysiological damageimmediately after the H-I injury; through the application of silver staining techniques andimage analysis to observe the dendritic development of the hippocampal CA1pyramidal cells;the Morris water maze was used to evaluate the learning and memory ability; at the same time,immunohistochemistry and western blot technique were applied to evaluate the expression ofVGluT1,NMDAR,ANMPR,synaptophisin,GLT1that relate to hippocampal synapsefunctions. The results were shown as follows:Part11．The hippocampal pyramidal cells electrophysiology characteristic changes happenedimmediately after hypoxic-ischemic brain damage. The excitability of pyramidal cell wasdecreased; the frequency of spontaneous excitatory postsynaptic currents (eEPSCs) wasincreased; the amplitude of excitatory postsynaptic currents (EPSCs) was no change while theduration of EPSCs was increased.2．There was no obvious effect of gorticosteroids on the amplitude and duration ofEPSCs in control and H-I injury group, but there was significant increase of EPSC amplitudeat right hippocampus in H-I injury group.3．Immediatly after the NHIE injury, the expression of GLT1which related to synapticwas decreased compare to control group, while the expression of NMDAR, AMPAR andsynaptophisin were unchanged.Part21．There was dendritic developmental disability of hippocampal CA1pyramidal cells inrat NHIE models.2．The total dendritic length and dendritic spine density of hippocampal pyramidal cellsas well as the density of neurofibrilla were decreased; and in the hippocampus that just sufferhypoxia injury (the right hippocampus of H-I injury group), the dendritic trees of pyramidalcells were overdevelopment.3．The corticosteroids therapy on NHIE could improve the dendritic development of thehippocampal pyramidal cells.Part31．Morris water maze results show that hypoxic-ischemic brain injury has obviousinfluence on the function of learning and memory in rat, there was no obvious therapeuticeffect of corticosteroids used immediatly after H-Iinjury.2．After hypoxic-ischemic brain injury, the expression of NMDAR1,VGluT1,synaptophisin that related to synaptic functions were decreased. The corticosteroids can partlyprevent the decreased of proteins expression, but it can not recovery to the normal controllevels. Based on the results, we could draw the following conclusions:1．Electrophysiological characteristic changes happened instantly in the hippocampuspyramidal cells of hypoxia ischemic brain injury rat models. The neuronal excitability wasdecreased. The increased concentration of extracellular glutamate may be contributing to theraised frequency of the EPSCs of pyramidal cells.2． After the neonatal hypoxic ischemic brain injury, pyramidal cell dendriticdevelopment of rat hippocampal CA1area was disability. The total dendritic length anddendritic spines density were decreased. From the dendritic tree developmental level of thehippocampus just suffering the hypoxia (the right hippocampus of the H-I injury rat), it couldbe deduced that the pyramidal cells of right hippocampus could compensat the lost function ofH-I injury hippocampus.3．The use of corticosteroid therapy on neonatal hypoxic-ischemic brain injury canimprove the development of hippocampus dendritic trees of rat models. It make the bilateralhippocampal neurons dendritic growth level tends to be unified.4．There was expressional reduction of some protein related to the synaptic functions andthis reduction was significant. This result reflected that the decrease of function waspersistent.5．Hypoxicischemic brain seriously damaged the function of learning and memory in rat,there was no significant improvement treated with corticosteroids after H-I injury.
|
PDF Full Text Request