Figure 3. Neuropathologic changes associated with i.c. CED of Lipoplatin™ or its “hollow” counterparts or free cisplatin (A).

(A) Lipoplatin™ (1.8 µg). Rat was euthanized 2 hr after CED. There is cerebral edema and a single focus of hemorrhage in the R cerebral hemisphere, adjacent to the medial boundary of the R lateral ventricle and another in the lateral hypothalamic area. (B) Lipoplatin™ (0.9 µg cisplatin). The rat was euthanized 4 days after CED. There is extensive necrosis with a dense infiltrate of foamy macrophages. (C) Lipoplatin™ (0.9 µg cisplatin) euthanized on d 4. There is a 6×4 mm zone of advanced necrosis with a peripheral zone of microglial reaction. There is edema of the neurophil and vacuolization, but no inflammatory response. (D) and (E) Lipoplatin™ “hollow” liposomes (100×). There is a 7×4 mm zone of hemorrhage associated with necrosis and edema of the neuropil. (E) There is an infiltrate of macrophages and hyperplasia of endothelial cells of adjacent small vessels. (F) Free cisplatin (3 µg), rats euthanized on d 7. Higher power (400×) view of (Fig. 4H). There is hemorrhage, necrosis and infiltration with lipid laden macrophages. Scattered larger blood vessels show early fibrin deposition in the walls.