Figure 4. Neuropathologic changes associated with i.c. CED of cisplatin containing CHEMS liposomes (A-E), their “hollow” counterparts (F), or free cisplatin (H).

(H&E) stained coronal sections at 400× magnification unless otherwise noted. (A) and (B) CHEMS – cisplatin, (4.8 µg), euthanized at 2 wks. (A) Although no necrosis is seen there are clear, possibly lipid containing vacuoles scattered reactive astrocytes and a mild infiltrate of macrophages. (B) There is focus of incipient necrosis and a moderate infiltrate of macrophages. Neurons consistent with late neuronal injury, proliferation of astrocytes and ependymal cells along the wall of the ventricle are also seen, but not in this photomicrograph. (C) and (D) CHEMS – cisplatin (9 µg), euthanized on d 10. There is focal intense inflammation with large numbers of macrophages, scattered lymphocytes, hemorrhage and necrosis and (E) prominent neovascularization. (F) and (G) “Hollow” CHEMS liposomes, euthanized on d 10. There is prominent necrosis with an intense inflammatory response consisting of lymphocytes and macrophages. Small vessels are engorged with blood and show reactive endothelial cells. (G) GFAP immunostaining revealed paraventricular foci of reactive astrogliosis. (H) Free cisplatin (3 µg), euthanized on d 7. Low power view (100×) shows a prominent focus (7×7 mm) of confluent hemorrhage with disruption of adjacent necrotic white matter.