INTRACEREBRAL MORPHOLOGICAL AND ULTRASTRUCTURAL ALTERATIONS AFTER INTRAVENOUS ADMINISTRATION OF Lonomia obliqua SPICULE EXTRACT IN RATS

SILVA, G.H.(1), HYSLOP, S.(1), CRUZ-HÖFLING, M.A.(2)

(1)Departamento de Farmacologia, F.C.M., (2)Departamento de Histologia e Embriologia, I.B., Universidade Estadual de Campinas (UNICAMP), Campinas, SP, Brasil.

Objective: Clinical reports have shown cerebral damage, including edema and intracerebral hemorrhage, after envenoming by Lonomia obliqua caterpillars. In this work, we investigated the neurotoxicity of L. obliqua spicule extract injected intravenously in rats.

Methods and Results: Morphological  and ultrastructural analyses were done using light and transmission electron microscopy 6 h, 18 h, 24 h and 72 h after i.v. injection of L. obliqua spicule extract (200 mg/kg). For ultrastructural analysis, lanthanum nitrate was used as an extracellular tracer to assess blood-brain barrier (BBB) breakdown. Six hours after envenoming, light microscopy showed cerebellar edema which decreased by 72 h. Intracerebral hemorrhage occurred in only one rat 6 h after extract injection. BBB breakdown was assessed by transmission electron microscopy based on the passage of extracellular tracer between brain capillary endothelial cells. BBB breakdown was observed in the cerebellum and hippocampus 18 h post-injection. The cerebellum was more sensitive to the venom than the hippocampus, as shown by the greater number of leaky capillaries. After 72 h, the number of capillaries showing BBB breakdown was lower than after 18 h.

Conclusion: The morphological and ultrastructural alterations observed indicate that Lonomia obliqua spicule extract has a neurotoxic action. Assays in vivo with purified fractions of the venom are necessary to identify the component responsible for these effects.

Financial support: CNPq, CAPES, FAPESP, FAEP.

CORRESPONDENCE TO:

MARIA ALICE DA CRUZ-HÖFLING, Rua Fernão de Magalhães 1017, Campinas, SP, CEP: 13087-130, Brasil, Email: hofling@unicamp.br