LOCAL NEUROTOXICITY OF HEMATOPORPHYRIN DERIVATIVE FOLLOWING INTRACEREBRAL INJECTION

The present study reports on toxicity of hematoporphyrin derivative (H pD) for normal brain tissue in vivo without the addition of light. Hem atoporphyrin derivative was injected by slow infusion in rat brains. H istological examination was carried out for intervals after HpD admini stration, ranging from 0 h to 15 days. Ultrastructural changes were ex aminated with transmission electron microscopy. The extent of the necr osis was determined for different HpD concentrations and compared with control animals infused with 0.9% saline. Leukocytic infiltration was observed at day 5. Transmission electron microscopy showed that nucle i of neurons were completely disintegrated 4 h after HpD administratio n. Furthermore disruption of myelin sheaths was observed. The extent o f the necrosis decreased with lower HpD doses. Injection of 2 mu g HpD in a volume of 4 mu L (0.5 mg/mL) resulted in a virtually equal exten sion of the tissue damage, as compared to the mechanical damage in the control animals caused by the infusion procedure.