Effect of Dysfunction of Myelination of Oligodendrocytes after Hypoxia-Ischemia on White Matter Injury in Immature Brain

Objective To investigate the role of oligodendrocytes(OLs) in the hypoxic-ischemic encephalopathy of immature rats.Methods Forty-eight 3-days old SD rats were divided into 2 groups:the experimental group and the control group.In the experimental group,the right common carotid artery of the immature rats were isolated and cut off,then they were put in the hypoxic box.However,in the control group,the right common artery of the immature rats were only isolated without other treatment.The specimen of brain tissue was achieved on 3 days,7 days,and 14 days after the surgery with heart perfusion separately.They were labeled as group A1/A2,B1/B2,C1/C2.Before the perfusion,the rats got 3 times of Brdu by intraperitoneal injection,every 4 hours once.Then the brain tissue was cut into slices after the fixing and dewatering.The brain section was dyed with Cresyl fast videt(CV) to evaluate the damage of brain.The immunohistochemistry staining of the brain section,targeting with neuron-glial antigen 2(NG-2),myelin basic protein(MBP),5-Bromo-2-deoxyUridine(Brdu),and Caspase-3 were performed.To investigate the role of OLS in the hypoxic-ischemic encephalopathy of immature rats.Results 1.There were significant differences between A1 group and A2 group(0.900±0.059 vs 0.970±0.015);B1 group and B2 group(0.870±0.039 vs 0.920±0.024);C1 group and C2 group(0.730±0.096 vs 0.920±0.039) in the ratio of brain area with the staining of CV(Pa0.05).Meanwhile,there were significant differences between A1 group and A2 group(0.870±0.028 vs 0.910±0.033)in the ratio of corpus callosum.There were no significant differences between B1 group and B2 group(0.920±0.030 vs 0.920±0.025),C1 group and C2 group(0.830±0.130 vs 0.850±0.076)(P0.05).2.The ratio of MBP positive area of the corpus callosum and the whole corpus callosum:which in the damage part and the contralateral part in B1 group were(0.32±0.17),(0.39±0.20);in group B2 was 0.51±0.11;which in the damage part and the contralateral part in C1 group were(0.71±0.07),(0.90±0.10);in C2 group was 0.88±0.13.There were significant differences between the damage part and the contralateral part at every time point(Pa0.05);and there were also significant differences between the experimental group and the control group at every time point(Pa0.05).3.The number of NG-2 positive cells at higher magnification:which in the damage part and the contralateral part in A1 group were(23.56±2.93),(18.11±3.19);in A2 group was(20.17±2.38);which in the damage part and the contralateral part in B1 group were(27.29±4.81),(22.88±5.31);in B2 group was(20.81±3.24);which in the damage part and the contralateral part in C1 group were(22.29±4.27),(16.04±4.17);in group C2(14.07±3.29).There were significant differences between the damage part and the contralateral part at every time point(Pa0.05);and there were also significant differences between the experimental group and the control group at every time point(Pa0.05).4.The number of Caspase-3 positive cells at higher magnification:which in the damage part and the contralateral part in A1 group were(68.67±6.60),(60.04±5.66);in A2 group was 40.21±7.93;which in the damage part and the contralateral part in B1 group were(59.13±10.22),(50.38±11.58);in B2 group was(48.17±4.27);which in the damage part and the contralateral part in C1 group were(70.13±16.11),(57.00±15.43);in C2 group was(62.42±13.56).There were significant differences between the damage part and the contralateral part at every time point(Pa0.05);and there were also significant differences between the experimental group and the control group at the first two time points(Pa0.05).5.The number of Brdu positive cells at higher magnification:in the damage part and the contralateral part in A1 group were(149.58±21.12),(126.92±7.23);in A2 group was(120.33±7.18);in the damage part and the contralateral part in B1 group were(89.04±20.42),(79.79±16.77);in B2 group was(85.83±6.05);in the damage part and the contralateral part in C1 group were(60.08±10.89),(53.25±8.02);in C2 group was(50.08±4.78).There were significant differences between the damage part and the contralateral part at the first two time points(Pa0.05);and there were also significant differences between the experimental group and the control group at the first two time points(Pa0.05).Conclusions The hypoxic-ischemic injury can lead to a deficit in mature,myelin-producing OLs and as a consequence,cerebral hypomyelination;and OLs are the main targets of the injury.