Effect of intracarotid infusion of etoposide with angiotensin II-induced hypertension on the blood-brain barrier and the brain tissue

Summary This study investigated the effects of the intracarotid infusion of etoposide in combination with angiotensin 11 (AT 11)-induced hypertension on the blood-brain barrier (BBB) and brain tissue in rats. Eighty rats were divided into five groups: Group 1, intravenous infusion of AT 11 to increase arterial blood pressure; Group 2, intracarotid infusion of etoposide at 22.5 mg/m² for 10 minutes; Group 3, intracarotid infusion of etoposide at 75.0 mg/m² for 10 minutes; Group 4, intracarotid infusion of etoposide at 75.0 mg/m² for 20 minutes; Group 5, intracarotid infusion of etoposide at 75.0 mg/m² for 10 minutes with AT 11-induced hypertension. Evans blue staining of the brain was used as a monitor of BBB disruption. Mean arterial blood pressure over the experimental period in Group 1 increased from 86.3 ± 1.3 mmHg (mean ± SEM) to 139.0 ± 2.4 mmHg, and Group 5 from 85.9 ± 1.8 mmHg to 137.3 ± 2.4 mmHg. None of the animals in Group 1 and 2 showed any obvious neurological change, while all the animals in Group 3, 4 and 5 exhibited diminished activity as their sole neurological change throughout the course of the experiment. Slight evidence of BBB disruption was seen in only 25% of the animals in Group 1. Significant BBB disruption was found in the animals in Group 2, 3, 4 and 5. No histological change was observed in any animal in Group 1 and 2. Demyelination, cerebral edema, and neuronal change on the infused hemisphere were observed in half of the animals in Group 3, 4 and 5, but no marked difference was observed among the three groups.At II-induced hypertension is unlikely to have an adverse effect by itself on the BBB and brain tissue. However, intracarotid infusion of high-dose etoposide is capable of producing BBB disruption and irreversible neuronal damage by itself irrespective of infusion rate. Modification of BBB and neuropathological change in case of intracarotid infusion of etoposide with AT 11-induced hypertension primarily caused by etoposide itself and not by the AT II-induced hypertension.