Blood-brain barrier disturbance following subarachnoid hemorrhage in rabbits

We studied disruption of the blood-brain barrier after experimental subarachnoid hemorrhage induced by an injection of 4 ml autologous arterial blood into the cisterna magna of rabbits. The animals were killed at 40 minutes, 6 hours, 1 day, 2 days, 4 days, or 6 days after subarachnoid hemorrhage. We assessed the integrity of the barrier function of intraparenchymal vessels in the ventral brain stem and cerebral hemispheres morphologically with transmission electron microscopy, using horseradish peroxidase as a tracer. In the ventral brain stem, which was in direct contact with the cisternal clots, markedly increased peroxidase staining toward the core of the brain stem was observed on the first day after subarachnoid hemorrhage. In an area of the cerebral hemispheres distant from the clots, barrier disturbance was prominent in the 6-hour specimens, and permeation of the tracer was spotty. From the distribution and morphological findings of these lesions, permeability changes in the ventral brain stem may have been caused by a direct effect of the cisternal clots; in the cerebral hemispheres, hemodynamic factors and changes in intracranial pressure associated with the elderly stages of subarachnoid hemorrhage seemed to be responsible. These results suggest that barrier disturbance associated with subarachnoid hemorrhage may be multifactorial in time course and location.