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LOCAL NEUROTOXICITY OF HEMATOPORPHYRIN DERIVATIVE FOLLOWING INTRACEREBRAL INJECTION
Authors:David P  Noske  Wouter  Kamphorst  John G  Wolbers Henricus J C M  Sterenborg
Institution:Department of Neurosurgery, Free University Hospital, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands;Department of Neuropathology, Free University Hospital, Amsterdam, the Netherlands;Laser Center, Academic Medical Center, Amsterdam, the Netherlands
Abstract:The present study reports on toxicity of hematoporphyrin derivative (HpD) for normal brain tissue in vivo without the addition of light. Hematoporphyrin derivative was injected by slow infusion in rat brains. Histological examination was carried out for intervals after HpD administration, ranging from 0 h to 15 days. Ultrastructural changes were examinated with transmission electron microscopy. The extent of the necrosis 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 nuclei of neurons were completely disintegrated 4 h after HpD administration. Furthermore disruption of myelin sheaths was observed. The extent of the necrosis decreased with lower HpD doses. Injection of 2 μg HpD in a volume of 4 μL (0.5 mg/mL) resulted in a virtually equal extension of the tissue damage, as compared to the mechanical damage in the control animals caused by the infusion procedure.
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