Safety of thrombolytic therapy with rt-PA and transcranial color Doppler ultrasound (TCCS) combined with microbubbles: A histopathologic study on rabbit brain tissues

ObjectiveTo evaluate effect of thrombolytic therapy with rt-PA (recombinant tissue plasminogen activator) and transcranial color Doppler ultrasound (TCCS) combined with microbubbles on histology of brain tissue.MethodsNew Zealand rabbits were subjected to TCCS based thrombolytic therapy, in 8 groups depending on dose of rt-PA, exposure duration of TCCS and presence of attenuation by skull bone window, 2 animals/group: (1) skull + 1/2 rt-PA + TCCS + MBs, 10 min, (2) skull + rt-PA + TCCS + MBs, 10 min, (3) skull + 1/2 rt-PA + TCCS + MBs, 20 min, (4) skull + rt-PA + TCCS + MBs, 20 min, (5) skull + 1/2 rt-PA + TCCS + MBs, 30 min, (6) skull + rt-PA + TCCS + MBs, 30 min, (7) 1/2 rt-PA + TCCS + MBs, 10 min, (8) 1/2 rt-PA + TCCS + MBs, 20 min. The brain tissues were harvested after therapies and submitted for microscopic, electronic microscope and immunohistochemical examination. The histological changes were scored.ResultsTCCS caused exposure duration dependent brain tissue damage. With attenuation by bone window, TCCS based therapies for 10–20 min caused minimal tissue damage. However, significant tissue damage was observed upon TCCS for 30 min in presence of skull bone window, presenting as hemorrhage, misdistribution of organelles, demyelination of nerve fibers, and thinning of basement membrane in blood–brain barrier, which was milder than that after 20 min of exposure to TCCS in absence of bone window. Dose of rt-PA did not affect brain histology in all groups.ConclusionShort treatment of brain tissue with TCCS through a bone window is relative safe. And skull bone window protected brain tissue from TCCS induced damage.