Blood-brain barrier breakdown following gliotoxic drug injection in the brainstem of Wistar rats

Ethidium bromide (EB) causes local astrocytic disappearance, with glia limitans disruption and supposed blood-brain barrier (BBB) breakdown The aim of this study was to investigate the BBB integrity after the injection of 0.1% EB (group E) or 0.9% saline solution (group C) into cisterna pontis of Wistar rats. Brainstem fragments were collected from 24 hours to 31 days post-injection for ultrastructural study and GFAP immuno-histochemical staining. Some animals received colloidal carbon ink by intravenous route at the same periods. In rats from group C, there was no sign of astrocyte loss and no leakage of ink from blood vessels in the injection site. In group E, astrocyte disappearance began at 48 hours and some areas were still devoid of astrocytic processes 31 days after. Leakage of carbon particles was seen from 48 hours to 7 days in the EB-induced lesions. Tight junctions did not show any detectable ultrastructural change due to the lack of perivascular astrocytes.