Objective To observe the expression of aquaporin-4 (AQP-4) mRNA and study the relationship between AQP-4,brain edema,pathological changes and uhrastructure of perihematoma tissue in intracerebral hemorrhage (ICH) patients.Methods Intracranial operation was performed via nonfunctional area with a funnel-like approach on 30 ICH patients.The brain tissue which must be removed 1 cm away the hematoma was removed within 12 hours for observation as normal brain tissue and taken as the control group (7 patients),and which of the brain tissue within 1 cm around hematoma was taken as the study specimens.The experimental group was subdivided into five groups according to the time interval after ICH;<6 hours (6 cases),6-12 hours (7 cases),12-24 hours (5 cases),24-72 hours (6 cases),and>72 hours (6 cases).Expression of the AQP-4 mRNA,brain edema,pathological and ultrastructural changes were observed with reverse transcription-polymerase chain reaction (RT-PCR),light microscope and electron microscope. Results The expression of the AQP-4 mRNA was not remarkable,the morphology and construction were basically normal in control group.The expression of AQP-4 mRNA was mild (1.17±0.41 ) and there was edema of neuroglia in the <6 hours group.After 6 hours,besides neuroglial edema,the expression of the AQP-4 mRNA was gradually obvious,capillary endothelial cells began to swell too,and tight junctions gradually began to loosen.In the 12 - 72 hours group the expression of the AQP-4 mRNA reached its peak (3.50 ± 0.55,3.60±0.55,both P< 0.01 ),and brain edema was most prominent,and electron microscopy showed that neurons,neuroglia,and capillary endothelial cells were markedly deformed.After 72 hours,the expression of AQP-4 mRNA gradually recovered,and brain cells showed less damage.On the 5th day the damage began to repair,and on the 8th day,the damage was basically repaired.The correlation analysis showed that there was a remarkable positive correlation between the expression of the AQP-4 mRNA and the degree of brain edema and the size of hematoma (r1=0.67,P<0.01;r2=0.44,P<0.05). Conclusion Secondary edema and brain damage may correlate with the expression of the AQP-4 mRNA in the perihematoma brain edema area. Removal of hematoma will help decrease the AQP-4 mRNA expression and brain edema damage in the early stage.
Key words:
intracerebral hemorrhage; brain edema; aquaporin; pathology; ultrastructure
Background In recent years, some researches had been conducted on the pathologic changes of the secondary injury of perihematoma in animal experiments, but only a few studies had been done on the dynamic pathologic and ultrastructural changes of the perihematoma in ICH patients. The unique contribution of our study is to investigate the dynamic pathologic and ultrastructural changes of the perihematoma in ICH patients and provide significant insights into how the pathophysiology and ultrastructures changed after ICH. Methods The written informed consents were obtained from the ICH patients or their relatives. 30 patients (the supertentorial hemotoma volume >30 ml and the cerebellar hemotoma volume >10 ml) were divided into 8 groups according to the time passed after ICH: <6 h (6 patients), 6~12h (7 patients) , 12~24 h (5 patients), 24~48 h (3 patients), 48~72 h (3 patients), 3~4 days group (3 patients), 5 days group (2 patients) and 8 days group (1 patient) and subjected to craniotomy for hemotoma evacuation. During the operation for the hemotoma's evacuation, a small amount of tissues that must be removed , which located at 1 cm near the hematoma, were taken as experimental groups; And the same tissues of 7 patients (<12 h), which were far from the hemotoma on the operational way, were taken as control group. The pathologic and ultrastructral changes were observed. Results The tissues of the control group were almost normal while the damages of the tissues from the experimental groups were slight in <6 h groups, more severe after 6h and got to the maximum between 24~48 h, recovered gradually after 72 h, became similar to the 6~12 h group on 5 th day, got better on 8 th day and resembled the 6 h group. Conclusions The injury of the perihematoma occurred in early stage, reached the peak level between 24 and 48 hours after ICH; which was consistent to the clinical nervous functional deficits in the ICH patients.