Changes Of Eelectroencephaphysiology In Newborn Piglets With Hypoxic-Ischemic Brain Damage During Selective Moderate Head Cooling Therapy

Mild hypothermia is regarded as one of the most potential methods for hypoxic-ischemic encephalopathy(HIE).Hypoxia-ishcemia may cause energy metabolism failure, excessive release of excitatory amino acid, influx of intracellular sodium and calcium and neuronal apoptosis, which in turn lead to the disorder of electroencephaphysiology.Maximum length sequences brainstem auditory evoked potential (MLS BAEP) is a recently developed technique to monitor cerebral function. Compared with the conventional BAEP it could effectively detect minor pathological changes of brainstem auditory pathway. MLS BAEP was used to evaluate the brainstem function of newborn infants who suffered perinatal asphyxia.EEG power spectra could quantitatively and objectively reflect brain activity by computer disposal based on conventional electroencephalogram. It could accurately and quantitatively reflect the function of all cortex regions.Amplitude integrated electroencephalogram (aEEG) is a simple and effective tool to monitor cerebral function, by which find early HIE and predict the severity.The study is to explore dynamic electroencephaphysiology changes in brainstem and cortex using novel electrophysiological technique (MLS BAEP, EEG power spectra and aEEG.) in newborn piglets after hypoxic-ischemic brain damage. From electroencephaphysiology respect of view, it is expected to demonstrate the pathophysiology of HIBD and the effect of mild hypothermia on HIBD.Part OneChanges of MLS BAEP in Newborn Piglets with Hypoxic-ischemic Brain Damage During Selective Moderate Head Cooling TherapyObjective To study the effect of selective moderate head cooling therapy on maximum length sequences brainstem auditory evoked potential (MLS BAEP) in newborn piglets with hypoxic-ischemic brain damage. Methods Twenty newborn piglets, aged 5-7 day old, were randomly divided into four groups: normothermic control group(n=4), hypothermic control group(n=4), HI group(n=6) and mild hypothermia-treated group(n=6). HI was induced through temporary occlusion of both carotid arteries, followed by mechanical ventilation with low concentration of oxygen (FiO2=0.06) for 30 minutes. Mild hypothermia was induced by equipment via circulating water. Nasopharyngeal temperature was reduced to 35°C and maintained for 24h in hypothermic group. Normal rectal temperature (39°C) was remained in normothermic group. MLS BAER was recorded and analyzed before HI, 2h, 12h, 24h, 36h, 48h, 60h, 72h, 4d, 7d, lOd, 13d andl5d after HI. Results MLS BAER variables (latency and interval) in normothermic control group did not show any significant changes during the first 7d. However, from day 10, except wave I latency, all other latencies and intervals in control group showed a tendency to decrease slightly. All latencies and intervals in hypothermic control group did not show any change during the first 7d before and after hypothermia. Compared with the normothermic control group, all latencies and intervals tended to increase significantly at 72h in HI group and reached peak values on day 7. From day 10, except wave I latency, all other latencies and intervals tended to decrease, but still differed significantly from those of the normothermic control group. MLS BAER variables did not reach normal values until day 15. Although all latencies and interpeak intervals in mild hypothermia-treated group tended to increase from day 7, they were still shorter than those of HI group. After 10 days, except wave I latency, all other latencies and interpeak intervals of mild hypothermia-treated group showed a tendency to decrease. Although the tendency to decrease was not significant, it was still shorter than that of HI group. Conclusions From day 10 except wave I latency, all other latencies and intervals in normothermic control group showed a tendency to decrease slightly. MLS BAEP variables in newborn piglets was not affected by hypothermia itself. Both peripheral and central auditory systems were disturbed by hypoxia-ischemia, which showed MLS BAER variables (all latencies and intervals) significant increased in newborn piglets. Insults in central brainstem auditory system reached peak on day 7 after injury. MLS BAER variables still did not reach to normal values until day 15. Selectivemoderate head cooling therapy significantly reduced brainstem damage induced by HI.Part twoChanges of Electroencephalography in Newborn Piglets with Hypoxic-Ischemic Brain Damage During Selective Moderate HeadCooling TherapyExperimental Research(l) Changes of EEG Frequency Power Spectrum in Newborn Piglets with Hypoxic-Ischemic Brain Damageduring Selective Moderate Head Cooling TherapyObjective To explore the effect of selective moderate head cooling therapy on EEG frequency power spectrum in neonatal piglets with hypoxic-ischemic brain damage. Methods Thirty-four newborn piglets were randomly divided into four groups: normothermic control group(n=7), hypothermic control group(n=9), HI group(n=9) and mild hypothermia-treated group(n=9). HIBD model and selective moderate head cooling therapy(SHC) were induced as described in the part one. EEG frequency power spectrum( a,P,6,8 )was recorded and analyzed before HI and 2h, 24h, 36h, 48h, 72h, 6d after HI. Results 8 frequency was dominate in normal newborn piglets , with 9 frequency and a frequency followed.EEG power was not significantly affected by hypothermia itself. The relative power and absolute power of the cortex did not show any significant differences in all region between HI group and control group at 2h after HI. However, compared with the normothermic control group,the relative power of 8 band of all cortex region in HI group increased significantly and that of a band decreased significantly within 6d after HI. In the meanwhile, the absolute power of the two bands were decreased significantly. Conclusions The results suggested that the cortex function of newborn piglet was severely disturbed after hypoxia-ischemia, which showed the relative power of slow wave frequency significantly increased and that of fast wave frequency significantly decreased. In the meanwhile, the absolute power decreased significantly. Selective moderate headcooling therapy decreased the relative power of slow wave frequency and increased that of fast wave frequency.In the meanwhile, it significantly increased the absolute power. The present experiment suggested that selective moderate head cooling therapy had neuroprotective effect on HIBD.Experimental Research(2) Changes of Amplitude Integrated Electroencephalogram in Newborn Piglets with Hypoxic-IschemicBrain Damage during Selective Moderate Head Cooling TherapyObjective To study the effect of selective moderate head cooling therapy on amplitude integrated electroencephalogram in newborn piglets with hypoxic-ischemic brain damage. Methods Randomized groups, HIBD model and selective moderate head cooling therapy(SHC) were induced as described in the part two.. The changes of aEEG wave band were continuously monitored in HI group and mild hypothermic group after insult. The incidence of abnormal aEEG were analyzed Results CNV(continuous normal voltage) was the indicator of normal brain function innormothermic control group. Compared with the normothermic control group, the incidence of mild abnormal aEEG, which was defined as DNV(discontinuous normal voltage) significantly increased in normal hypothermic group during the hypothermia treatment (24h). However, aEEG recovered to normal as temperature went up The incidence of severe abnormal aEEG significantly increased at 20min during HI.The aEEG recovered to normal in most of animals at 2h after HI. However, compared with the treatment group, the incidence of severe abnormal aEEG [CLV (continuous low voltage)> BS (burst-suppression)n FT (flat tracing) ] significantly increased again after 24h-48h in the HI group. The incidence of severe abnormal aEEG (CLVn BS> FT) in mild hypothermic group were significantly lower than those in HI group. The incidence of recovering to normal aEEG significantly increased in mild hypothermic group after 6d. Conclusions The severe abnormal aEEG occurred twice at 20min during HI and 24h-48h after HI, which indicated that there were two stages of neuron injury (primary and secondary) after HI. Selective moderate head cooling therapy significantly decreased the incidence of severe abnormal aEEG and promoted the recovery of electroencephaphysiology.