A breakdown of the blood-brain barrier is associated with optic nerve regeneration in the frog

We have examined the integrity of the blood-brain barrier during optic nerve regeneration in the frog Litoria (Hyla) moorei using rhodamine B-labeled bovine serum albumin (RBA). A transient localized breakdown of the blood-brain barrier was observed between 1 and 5 weeks after extracranial optic nerve crush. The zone of breakdown progressed along the experimental optic nerve, ascended the opposite optic tract, and swept rostro-caudally across the tectum contralateral to the crushed nerve. By 7 weeks, the blood-brain barrier was once again intact along the length of the optic pathway. In a concurrent series of frogs, regenerating optic axons were visualized by anterograde transport of horseradish peroxidase (HRP). At each stage examined, the region reached by the front of regenerating axons corresponded to that in which the blood-brain barrier had been shown to break down. In contrast to the results after nerve crush, the blood-brain barrier remained intact along the length of the optic pathway following optic nerve ligation to prevent regeneration. We conclude that the breakdown of the blood-brain barrier which occurs during optic nerve regeneration in the frog is triggered by the regenerating axons.