Abstract： ObjectiveThe mechanism of neonatal hypoxicischemic brain damage (HIBD) remains unclear and effective treatment approach is limited for this disorder. Many studies have shown that tissuetype plasminogen activator (tPA) plays an important role in nervous system. This study investigated the effect of tPA in HIBD in neonatal rats.MethodsSevendayold Wistar rat pups were used for the RiceVannucci model of neonatal hypoxiaischemia (HI). Brain samples were collected 1, 4, and 24 hrs after HI. FITCDextran was injected into the left ventricle of pups after HI to observe reperfusion defects of the neonatal brain. RTPCR and tPA zymogram were used to detect the expression and activity of tPA. Double immunostaining, terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and DAPI staining were used to detect the expression of integrin GPIIb and fibrin and neuronal apoptosis. ResultsFITCDextran perfusion analysis indicated there was obvious infarct area in the neonatal brain and the expression of integrin GPIIb and fibrin increased significantly 1 hr after HI compared with the contralateral side. The infarct area decreased and the expression of integrin GPIIb and fibrin were reduced 4 hrs after HI. The expression and activity of tPA increased significantly in neonatal rats after HI, and peaked at 4 hrs after HI. The number of apoptotic neural cells increased progressively with the prolonged reperfusion time following HI. ConclusionsThe increase of tPA in the acute phase after HIBD may be helpful to clot dissolving, but it induces neuronal apoptosis and aggravates brain injury.
