ABSTRACT
Mitochondrial permeability transition pore plays a central role in alterations of mitochondrial structure and function,leading to neuronal injury,which is a nonspecific,voltage dependence of complex channel.Hypoxia-ischemia can affect the function of mitochondria,causing mPTP permeability change and leading to cell death.Hypoxia-ischemia brain injury(HIBI) which is caused by perinatal asphyxia threatens neonatal life and leads to neurological sequelae of severe diseases.And mitochondrial dysfunction plays an important role in HIBI.This paper mainly elaborates the relationship between the mPTP and HIBI.
ABSTRACT
Objective To evaluate the effects of isoflurane postconditioning on mitochondrial permeability transition pore (mPTP) in brain tissues of neonatal rats with hypoxic-ischemic brain injury.Methods One hundred and twenty 7-day-old Sprague-Dawley rats,weighing 12-16 g,were randomly divided into 4 groups (n =30 each) using a random number table:sham operation group (group S),isoflurane group (group I),hypoxicischemic brain injury group (group HIBI),and hypoxic-ischemic brain injury + isoflurane postconditioning group (group HI).To establish hypoxic-ischemic brain injury model in the neonatal rats,the left common carotid artery ligation was carried out,and then the rats were exposed to 8％ O2 + 92％ N2 at 37 ℃ for 2 h in HIBI and HI groups.The rats inhaled 1.5 ％ isoflurane for 30 min after the model was established in group HI.The rats only inhaled 1.5％ isoflurane for 30 min in group I.At 24 h after the model was established,10 rats taken out randomly in each group were sacrificed and brains were removed to detect mPTP opening.At 7 days after the model was established,the survival rate was recorded in the rest rats.The rats were then sacrificed and brains were removed and the right and left cerebral hemispheres were weighed separately,and the ratio between left/right cerebral hemispheres was calculated.The density of normal neurons in ventral posterior inferior thalamic nucleus and hippocampal CA3 region in the left and right cerebral hemispheres were measured and the ratios of the density of normal neurons in the left to right cerebral hemisphere were calculated.Results There was no significant difference in the survival rate between the four groups (P ＞ 0.05).Compared with group S,the ratios of the density of normal neurons in the left to right cerebral hemisphere,weight of left cerebral hemisphere,and ratio between left/right cerebral hemispheres were significantly decreased,and mPTP opening was increased in group HIBI (P ＜ 0.05),and no significant changes were found in the parameters mentioned above in group I (P ＞ 0.05).Compared with group HIBI,the ratios of the density of normal neurons in the left to right cerebral hemisphere,weight of left cerebral hemisphere,and ratio between left/right cerebral hemispheres were significantly increased,and mPTP opening was decreased in group HI (P ＜ 0.05).Conclusion The mechanism by which isoflurane postconditioning reduces hypoxic-ischemic brain injury may be related to inhibition of mPTP opening in brain tissues of neonatal rats.
ABSTRACT
Objective To evaluate the effects of isoflurane postconditioning on long-term cognitive function of neonatal rats with hypoxic-ischemic brain injury (HIBI).Methods Sixty 7-day-old Sprague-Dawley rats,weighing 12-16 g,were randomly divided into 4 groups (n =15 each) using a random number table:sham operation group (group Ⅰ),isoflurane postconditioning group (group Ⅱ),cerebral hypoxia-ischemia group (group Ⅲ),and isoflurane postconditioning after cerebral hypoxia-ischemia group (group Ⅳ).Brain ischemia was induced by permanent ligation of the left common carotid artery followed by inhalation of 8 ％ O2-92 ％ N2 for 2 h at 37 ℃ in Ⅲ and Ⅳ groups.In Ⅰ and Ⅱ groups,the left common carotid artery was only isolated but not ligated.The rats inhaled 1.5％ isoflurane in 30％ O2-70％ N2 for 30 min starting from 2 h of hypoxia in Ⅱ and Ⅳ groups.The rats were exposed to 30％ O2-70％ N2 for 30 min in Ⅰ and Ⅲ groups.Morris water maze test was carried out at 30-35 days after HIBI.The escape latency,swimming speed,swimming distance,the number of times the animals crossing the platform quadrant,the percentage of time spent in the platform quadrant and the percentage of swimming distance in the platform quadrant were recorded.The animals were sacrificed after Morris water maze test.The density of normal neurons in ventral posterior inferior thalamic nucleus and hippocampal CA3 region in left and right cerebral hemisphere was measured and the ratio of the density of normal neurons in the left to right cerebral hemisphere was calculated.Results Compared with group Ⅰ,the escape latency was significantly prolonged at 30-34 days after HIBI in group Ⅲ and at 31 and 34 days after HIBI in Ⅳ group,the number of times the animals crossing the platform quadrant,percentage of time spent in the platform quadrant,percentage of swimming distance in the platform quadrant,and ratio of the density of normal neurons in the left to right cerebral hemisphere were decreased at day 35 after HIBI in group Ⅲ,no significant changes were found in the number of times the animals crossing the platform quadrant,percentage of time spent in the platform quadrant,and percentage of swimming distance in the platform quadrant,and the ratio of the density of normal neurons in the left to right cerebral hemisphere was decreased at day 35 after HIBI in group Ⅳ,and no significant changes were found in the parameters mentioned above in group Ⅱ.Compared with group Ⅲ,the escape latency was significantly shortened at 31-34 days after HIBI,and the number of times the animals crossing the platform quadrant,percentage of time spent in the platform quadrant,percentage of swimming distance in the platform quadrant,and ratio of the density of normal neurons in the left to right cerebral hemisphere were increased at day 35 after HIBI in group Ⅳ.There was no significant difference in the swimming speed and swimming distance at day 35 after HIBI between groups.Conclusion Isoflurane postconditioning can improve long-term cognitive function of neonatal rats with HIBI.