Local neurotoxicity of hematoporphyrin derivative following intracerebral injection.
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 examined 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 micrograms HpD in a volume of 4 microL (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.
Noske
D P
DP
Department of Neurosurgery, Free University Hospital, Amsterdam, The Netherlands.
Kamphorst
W
W
Wolbers
J G
JG
Sterenborg
H J
HJ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D017324:Hematoporphyrin Derivative / Q000008:administration & dosage / Q000633:toxicity*; D007263:Infusions, Parenteral; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D009336:Necrosis; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D009498:Neurotoxins / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013238:Stereotaxic Techniques
D009498:Neurotoxins; D017324:Hematoporphyrin Derivative