The Initial Research About The Effect Of Tissue Plasminogen Activator On Neural Repair

Objectives To explore the effect of tissue plasminogen activator on nerual repair after thrombolysis without recanalization.Methods 270 healthy male adult SD rats were randomly assigned into the experiment group (tpa group), the control group (ischemia group) and the sham-operation group (sham group). Each group was divided into five subgroups: 1day(1d), 3days(3d), 7days (7d) ,14days (14d)and 30days( 30d ). Permanent middle cerebral artery occlusion animal models were induced by electric coagulation. Animals in the tpa group received tail-intravenous injection of r-tpa ( 20mg/kg ) 3 hours after cerebral ischemia. Animals in the other two groups suffered the same dose of saline 3 hours after cerebral ischemia. At each time point, rats were scored as standard neurobehavioral tests and then sacrificed for the estimate of brain water content, TUNEL. Brdu and Nestin positive cells were tested by immunohistochemistry. Western blot and RT-PCR were used to exam the expression of Nestin and its mRNA producs.Results (1)Compared with the sham operation group, animals of both the ischemia group and the tpa group got neurologic deficit. In the tpa group, the neurologic deficit aggravated at 3d ,7d, 14d, 30d compared with the ischemia group(P<0.05). Especially at 3d and 30d, rats in the tpa group performed significantly more error reactions in Y-maze compared with the ischemia group(P<0.01); (2)Infarct volumes of the tpa group increased based on the ischemia group at 1d, 3d, 7d(P<0.05). And there was significant difference between those two groups at 3d(P<0.01); (3)Animals of both the ischemia group and the tpa group presented brain edema after cerebral ischemia. Brain water content in the tpa group showed significant higher than that of the ischemia group at 1d and 3d( P<0.01 ); (4) TUNEL positive cells appeared both in the ischemia group and the tpa group after acute ischemia. The numbers of TUNEL positive cells in the tpa group were significantly higher than that of the ischemia group at each time point(P<0.01); (5) Brdu positive cells and Nestin positive cells also presented both in the ischemia group and the tpa group within 1d after ischemia. In the tpa group, Brdu and Nestin positive cells in hippocamp or around ischemia decreased at 7d compared with the ischemia group;(6)Compared with the ischemia group, the expression of Nestin and its mRNA producs in hippocamp or around ischemia decreased at 7d(P<0.05). And there was significant difference between those two groups at 14d(P<0.01)Conclusions If there isn't available reperfusion after tpa thrombolysis on rats suffered from cerebral ischemia, 1) rats will get worse neurologic deficit than those undergo merely ischemia, and presented aggravated cognitive deficit at later stage; 2)infarct volume gets larger than those undergo merely ischemia ; 3) brain edema will becomes aggravated; 4) neuron apoptosis increases and neural stem cells decreases in hippocamp or around ischemia.