Canaud et al. (2005) investigated the pharmacological toxicity of PF-5070 in rabbits [9]. Rabbits were given the low (4 μL/kg) or intermediate dose (40 μL/kg) exhibited generalized malacia of the cerebrum and cerebellum. Notably, one animal showed

horizontal nystagmus and pulmonary infarcts were detected in some rabbits given the intermediate dose. Neurologically selleck inhibitor positive animal in the intermediate and high dose (160 μL/kg) groups showed hemorrhagic or ischemic damage in the cerebrum and cerebellum. The necrosis was sharply demarcated from adjacent viable tissue, a characteristic morphologic sign of ischemic infarct. Histopathologic findings from other organs in their study were extensive pulmonary edema, hemorrhages and infarction, and disseminated patchy necrosis of kidney, liver and spleen. In our study, SpO2 was Selleckchem Doramapimod remarkably decreased in both the PL and AA groups without histological damage. There was no macrophage phagocytosis of MBs or necrosis in the lungs, liver, spleen or kidneys. These phenomena may have been due to transient pulmonary alveolar occlusion while intravascular SPNs were present before they were excreted to the air. This speculation

could be extended to the animal with transient nystagmus in the AA group without cerebellum and brain stem damage. According to the study by Canaud et al. and our study, i.v. administration of PFC in rabbits might have the potential to cause occlusion within the vertebrobasilar system [9]. Moreover, one animal in the PL group Rucaparib that died after injection did not appear to have leukocyte aggregation or macrophage hypertrophy in the lungs [12]. However, the causes may also be attributable to delayed allergic reaction or some other unknown factor related to SPN injection. In summary, the

side effects of our newly developed SPNs are reversible respiratory disturbance and transient horizontal nystagmus without permanent neurological deficits, and biochemical changes in the plasma. One animal in the PL group died apparently of delayed shock. The most noteworthy point in this study is that no pathological damage due to gas embolism was found in any organs, including the brain tissue of case that developed temporary nystagmus. Our next challenges for novel neurological US therapies including sonothrombolysis are further evaluation of the safety administration dosages, other kinds of SPNs, and research into transcranial US trigger conditions which can convert SPNs into MBs in the cerebrovascular system. No permanent neurological deficit, biochemical changes in plasma, or histological damage were observed after injection of the two SPNs in surviving animals. One animal in the PL group died of delayed shock 2 days after injection. This study was supported, in part, by the New Energy and Industrial Technology Development Organization, Japan.